Abstract:

Behavioral interventions have been essential components of HIV prevention approaches, especially those aimed to promote safe sexual practices. We conducted a comprehensive literature search without language restrictions between 1980 and July 2014 to identify randomized controlled trials or controlled studies investigating behavioral interventions which: included women living with HIV; focused on condom use promotion; presented/analyzed outcomes by gender; used a 3-month follow-up or more; and considered at least one HIV-related behavioral or biological outcome. Eight studies comprising a total of 1,355 women living with HIV were included in the meta-analyses, and 13 studies were qualitatively described. When compared to standard care or minimal support intervention, behavioral interventions did not demonstrate an effect on increasing consistent condom use at the 3-month follow-up (RR = 0.92; 95%CI: 0.73, 1.16; p = 0.48), 6-month follow-up (RR = 1.13; 95%CI: 0.96, 1.34; p = 0.15), and 12-month follow-up (RR = 0.91; 95%CI: 0.77, 1.08; p = 0.30). Behavioral interventions also failed to reach positive effect in reduction of unprotected sexual intercourse at 6-months (MD = -1.80; 95%CI: -4.21, 0.62; p = 0.14) and 12-months follow-up (MD = -1.39; 95%CI: -2.29, 0.21; p = 0.09). These findings should be interpreted with caution since they are based on a few small trials. New researches are needed to assess the potential gains from a combination of interventions that promote safe sexual behavior with a harm reduction and gender approach, particularly in developing countries where HIV infection rates remain high.

Keywords:
Clinical Trial; Sexual Behavior; HIV; Women

Resumo:

As intervenções comportamentais têm sido componentes essenciais das abordagens de prevenção do HIV, especialmente daquelas que visam promover práticas sexuais seguras. Realizamos uma pesquisa bibliográfica abrangente sem restrições de linguagem entre 1980 e julho de 2014, visando identificar ensaios randomizados e não randomizados que investigassem intervenções comportamentais que: incluíssem mulheres vivendo com HIV; focassem na promoção do uso de preservativo; apresentassem ou analizassem resultados por gênero; realizasse acompanhamento por três meses ou mais; e considerasse pelo menos um resultado comportamental ou biológico relacionado ao HIV. Oito estudos com um total de 1.355 mulheres vivendo com HIV foram incluídos nas meta-análises e 13 estudos foram qualitativamente descritos. Quando comparadas com o tratamento padrão ou intervenção mínima de apoio, as intervenções comportamentais não demonstraram efeito no aumento do uso do preservativo no seguimento de 3 meses (RR = 0,92; IC95%: 0,73, 1,16; p = 0,48), no seguimento de 6 meses (RR = 1,13; IC95%: 0,96, 1,34; p = 0,15), e no seguimento de 12 meses (RR = 0,91; IC95%: 0,77, 1,08; p = 0,30). Intervenções comportamentais também não demonstraram efeito positivo na redução de relações sexuais desprotegidas aos 6 meses (MD = -1,80; IC95%: -4,21, 0,62; p = 0,14) e aos 12 meses de seguimento (MD = -1,39; IC95%: -2,29, 0,21; p = 0,09). Estes resultados devem ser interpretados com cautela, uma vez que se baseiam em poucos estudos. São necessárias novas pesquisas para avaliar os potenciais ganhos de uma combinação de intervenções que promovam comportamentos sexuais seguros, com uma abordagem de gênero e de redução de danos, particularmente em países em desenvolvimento onde as taxas de infecção pelo HIV permanecem altas.

Palavras-chave:
Ensaio Clínico; Comportamento Sexual; HIV; Mulheres

Resumen:

Las intervenciones comportamentales han sido componentes esenciales de los enfoques de prevención del VIH, especialmente de aquellos que tienen por objetivo promover prácticas sexuales seguras. Realizamos una investigación bibliográfica amplia, sin restricciones de lengua, entre 1980 y julio de 2014, teniendo por objetivo identificar ensayos randomizados controlados o estudios controlados que investigaran intervenciones comportamentales que: incluyeran a mujeres viviendo con VIH; se enfocaran en la promoción del uso de preservativo; presentaran o analizaran resultados por género; realizara un seguimiento durante tres meses o más; y considerara -por lo menos- un resultado comportamental o biológico relacionado con el VIH. Ocho estudios con un total de 1.355 mujeres viviendo con VIH se incluyeron en los metaanálisis y 13 estudios fueron cualitativamente descritos. Cuando se comparan con el tratamiento patrón o intervención mínima de apoyo, las intervenciones comportamentales no demostraron un efecto en el aumento del uso del preservativo en el seguimiento de 3 meses (RR = 0,92; IC95%: 0,73, 1,16; p = 0,48), en el seguimiento de 6 meses (RR = 1,13; IC95%: 0,96, 1,34; p = 0,15), y en el seguimiento de 12 meses (RR = 0,91; IC95%: 0,77, 1,08; p = 0,30). Las intervenciones comportamentales tampoco demostraron un efecto positivo en la reducción de relaciones sexuales desprotegidas a los 6 meses (MD = -1,80; IC95%: -4,21, 0,62; p = 0,14) y a los 12 meses de seguimiento (MD = -1,39; IC95%: -2,29, 0,21; p = 0,09). Estos resultados deben ser interpretados con cautela, ya que se basan en pocos ensayos. Es necesaria una nueva investigación para evaluar las potenciales ganancias de una combinación de intervenciones que promuevan comportamientos sexuales seguros, con un enfoque de género y de reducción de daños, particularmente en países en desarrollo, donde las tasas de infección por el VIH permanecen altas.

Palabras-clave:
Ensayo Clínico; Conducta Sexual; VIH; Mujeres

Background

HIV infection rates among women increased greatly in the 1990s and have remained stable since then. In 2014, women accounted for half of the 36.9 million cases of HIV infection in the world, mainly as a result of heterosexual transmission ¹1. World Health Organization. Global summary of the HIV/AIDS epidemic 2014. http://www.who.int/hiv/data/epi_core_july2015.png?ua=1.
http://www.who.int/hiv/data/epi_core_jul... . Southern Africa is the epicenter of an epidemic marked by profound gender inequality, with HIV infection rates in women up to eight times higher than in men ²2. Harrison A, Colvin CJ, Kuo C, Swartz A, Lurie M. Sustained high HIV incidence in young women in Southern Africa: social, behavioral, and structural factors and emerging intervention approaches. Curr HIV/AIDS Rep 2015; 12:207-15.. In Brazil, 35% of all AIDS cases reported in 2013 were in women (13,934 out of 39,501), or a female-to-male ratio of 1:1.8 for persons living with AIDS ³3. Ministério da Saúde. Boletim epidemiológico AIDS/DST 2014. Brasília: Ministério da Saúde; 2014..

The large number of HIV cases in women has dramatic public health consequences. Women face challenges to interrupt the HIV transmission chain, prevent mother-to-child transmission, and maintain their own health. These challenges directly affect their sexual practices. Women living with HIV are at increased risk for sexually transmitted infections (STI) ⁴4. Landes M, Thorne C, Barlow P, Fiore S, Malyuta R, Martinelli P, et al. Prevalence of sexually transmitted infections in HIV-1 infected pregnant women in Europe. Eur J Epidemiol 2007; 22:925-36.^{), (5}5. McClelland RS, Lavreys L, Katingima C, Overbaugh J, Chohan V, Mandaliya K, et al. Contribution of HIV-1 infection to acquisition of sexually transmitted disease: a 10-year prospective study. J Infect Dis 2005; 191:333-8., cervical dysplasia, and genital cancer ⁶6. Lehtovirta P, Paavonen J, Heikinheimo O. Risk factors, diagnosis and prognosis of cervical intraepithelial neoplasia among HIV-infected women. Int J STD AIDS 2008; 19:37-41.^{), (7}7. Oliveira PM, Oliveira RP, Travessa IE, Gomes MV, Santos ML, Grassi MF. Prevalence and risk factors for cervical intraepithelial neoplasia in HIV-infected women in Salvador, Bahia, Brazil. São Paulo Med J 2010; 128:197-201.. Concurrent STI and HIV also increase the risk of female-to-male HIV transmission during sexual intercourse ⁵5. McClelland RS, Lavreys L, Katingima C, Overbaugh J, Chohan V, Mandaliya K, et al. Contribution of HIV-1 infection to acquisition of sexually transmitted disease: a 10-year prospective study. J Infect Dis 2005; 191:333-8. and the risk of mother-to-child HIV transmission by pregnant women. Furthermore, some STI during pregnancy pose potential risk of congenital problems, for example maternal syphilis ⁸8. Departamento de DST, Aids e Hepatites Virais, Secretaria de Vigilância em Saúde, Ministério da Saúde. Recomendações para profilaxia da transmissão vertical do HIV e terapia antirretroviral em gestantes. Brasília: Ministério da Saúde; 2010..

Healthy sexual behaviors are important buffers against the challenges faced by women living with HIV. Protected sexual intercourse through consistent condom use has been described as the most effective way to prevent both STI and HIV transmission ⁹9. World Health Organization; Joint United Nations Programme on HIV/AIDS; United Nations Population Fund. Position statement on condoms and HIV prevention, 2014. Geneva: World Health Organization; 2014.. Despite positive advances (expansion of treatment and HIV testing) showed in the "15 by 15" report ¹⁰10. Joint United Nations Programme on HIV/AIDS. "15 by 15" - a global target achieved. Geneva: Joint United Nations Programme on HIV/AIDS; 2015. of the Global AIDS Response, sex protected by condom use remains a challenge. The focus on treatment as prevention has achieved recognized success; however, detectable HIV viral loads and imperfect adherence to antiretroviral therapy (ART) were not uncommon. Barrier methods such as condoms remain necessary to achieve broad reduction in HIV and other STI ¹¹11. Weeks MR, Zhan W, Li J, Hilario H, Abbott M, Medina Z. Female condom use and adoption among men and women in a general low-income urban U.S. population. AIDS Behav 2015; 19:1642-54.^{), (12}12. Shuper PA, Kiene SM, Mahlase G, MacDonald S, Christie S, Cornman DH, et al. HIV transmission risk behavior among HIV-positive patients receiving antiretroviral therapy in KwaZulu-Natal, South Africa. AIDS Behav 2014; 18:1532-40., considering that sexual transmission is responsible for most of new HIV cases ⁹9. World Health Organization; Joint United Nations Programme on HIV/AIDS; United Nations Population Fund. Position statement on condoms and HIV prevention, 2014. Geneva: World Health Organization; 2014..

Among women, although the prevalence of sexual risk behavior generally declines after HIV diagnosis, a substantial group (30-40%) continues to engage in unprotected sexual intercourse ¹³13. Cicconi P, Monforte A, Castagna A, Quirino T, Alessandrini A, Gargiulo M, et al. Inconsistent condom use among HIV-positive women in the "Treatment as Prevention Era": data from the Italian DIDI study. J Int AIDS Soc 2013; 16:18591.^{), (14}14. Weinhardt LS, Kelly JA, Brondino MJ, Rotheram-Borus MJ, Kirshenbaum SB, Chesney MA, et al. HIV transmission risk behavior among men and women living with HIV in 4 cities in the United States. J Acquir Immune Defic Syndr 2004; 36:1057-66.. Women are also less likely to use a condom when they have an HIV-infected partner than when the partners are HIV-negative or with unknown HIV status. Findings from a cross-sectional study including 978 women showed that 51% of unprotected sexual intercourse among HIV-infected women in the previous three months involved an HIV-infected partner (30% of unprotected sexual intercourse occurred with an HIV-uninfected partner, and 26% with a partner of unknown status) ¹⁴14. Weinhardt LS, Kelly JA, Brondino MJ, Rotheram-Borus MJ, Kirshenbaum SB, Chesney MA, et al. HIV transmission risk behavior among men and women living with HIV in 4 cities in the United States. J Acquir Immune Defic Syndr 2004; 36:1057-66.. Studies also reported higher levels of unprotected sex among women after ART initiation when compared to women before treatment initiation, independently of therapeutic response ¹⁵15. Wilson TE, Gore ME, Greenblatt R, Cohen M, Minkoff H, Silver S, et al. Changes in sexual behavior among HIV-infected women after initiation of HAART. Am J Public Health 2004; 94:1141-6., suggesting that beliefs regarding lower levels of infectivity under ART are also associated with less frequent condom use.

In addition to these findings, it is crucial to highlight the social determinants surrounding unprotected sexual behavior in women. Gender inequities have been cited as the main reason for unprotected sexual practices among women living with HIV ¹⁰10. Joint United Nations Programme on HIV/AIDS. "15 by 15" - a global target achieved. Geneva: Joint United Nations Programme on HIV/AIDS; 2015.^{), (12}12. Shuper PA, Kiene SM, Mahlase G, MacDonald S, Christie S, Cornman DH, et al. HIV transmission risk behavior among HIV-positive patients receiving antiretroviral therapy in KwaZulu-Natal, South Africa. AIDS Behav 2014; 18:1532-40.^{), (16}16. Santos NJ, Barbosa RM, Pinho AA, Villela WV, Aidar T, Filipe EMV. Contextos de vulnerabilidade para o HIV entre mulheres brasileiras. Cad Saúde Pública 2009; 25 Suppl 2:S321-33., including precarious socioeconomic conditions, low educational level, gendered power imbalances, intimate partner violence, and partner alcohol abuse. Reproductive intentions have also been emphasized as a reason for not using condoms ¹⁷17. Finocchario-Kessler S, Sweat MD, Dariotis JK, Trent ME, Kerrigan DL, Keller JM, et al. Understanding high fertility desires and intentions among a sample of urban women living with HIV in the United States. AIDS Behav 2010; 14:1106-14..

In order to avoid sexual risk behavior, programs for social and behavioral change have been encouraged and are seen as an essential component of HIV prevention approaches ¹⁸18. Joint United Nations Programme on HIV/AIDS. Social and behaviour change programming. Geneva: Joint United Nations Programme on HIV/AIDS; 2014.. The effectiveness of such prevention programs in increasing condom use and preventing HIV infection was demonstrated in a previous meta-analysis with HIV-seronegative participants ¹⁹19. Scott-Sheldon LAJ, Huedo-Medina TB, Warren MR, Johnson BT, Carey MP. Efficacy of behavioral interventions to increase condom use and reduce sexually transmitted infections: a meta-analysis, 1991 to 2010. J Acquir Immune Defic Syndr 2011; 58:489-98.. Considering people living with HIV, behavioral interventions have focused on reducing sexual risk behaviors and coping with other challenges of living with HIV ²⁰20. Faria ER, Carvalho FT, Gonçalves TR, Moskovics JM, Piccinini CA. Intervenções psicológicas para pessoas vivendo com HIV/Aids: modelos, resultados e lacunas. Interam J Psychol 2011; 45:339-50.^{), (21}21. Crepaz N, Lyles CM, Wolitski RJ, Passin WF, Rama SM, Herbst JH, et al. Do prevention interventions reduce HIV risk behaviours among people living with HIV? A meta-analytic review of controlled trials. AIDS 2006; 20:143-57.. Behavioral interventions to increase antiretroviral adherence ²²22. Johnson MO, Charlebois E, Morin SF, Remien RH, Chesney MA; The NIMH Healthy Living Project Team. Effects of a behavioral intervention on antiretroviral medication adherence among people living with HIV: the Healthy Living Project randomized controlled study. J Acquir Immune Defic Syndr 2007; 46:574-80., disclosure of HIV diagnosis to sex partners ²³23. Serovich JM, Reed S, Grafsky EL, Andrist D. An intervention to assist men who have sex with men disclose their serostatus to casual sex partners: results from a pilot study. AIDS Educ Prev 2009; 21:207-19., and promotion of mental health ²⁴24. Balfour L, Kowal J, Silverman A, Tasca GA, Angel JB, Macpherson PA, et al. A randomized controlled psycho-education intervention trial: improving psychological readiness for successful HIV medication adherence and reducing depression before initiating HAART. AIDS Care 2006; 18:830-8. have shown promising results. Regarding sexual risk behaviors, studies showed that behavioral interventions can reduce unprotected sexual practices among people living with HIV ²⁵25. Gore-Felton C, Rotheram-Borus MJ, Weinhardt LS, Kelly JA, Lightfoot M, Kirshenbaum SB, et al. The Healthy Living Project: an individually tailored, multidimensional intervention for HIV-infected persons. AIDS Educ Prev 2005; 17:21-39.^{), (26}26. Healthy Living Project Team. Effects of a behavioral intervention to reduce risk of transmission among people living with HIV: the Healthy Living Project randomized controlled study. J Acquir Immune Defic Syndr 2007; 44:213-21.. The effectiveness is also attested by meta-analyses, especially when intervention includes skills training ²¹21. Crepaz N, Lyles CM, Wolitski RJ, Passin WF, Rama SM, Herbst JH, et al. Do prevention interventions reduce HIV risk behaviours among people living with HIV? A meta-analytic review of controlled trials. AIDS 2006; 20:143-57.^{), (27}27. Johnson BT, Carey MP, Chaudoir SR, Reid AE. Sexual risk reduction for persons living with HIV: research synthesis of randomized controlled trials, 1993 to 2004. J Acquir Immune Defic Syndr 2006; 41:642-50.. Interventions guided by longer and more intensive behavioral theories were found to be more effective at promoting protected sexual intercourse. One-to-one interventions by healthcare providers in medical care settings were also associated with a reduction in unprotected sex ⁶6. Lehtovirta P, Paavonen J, Heikinheimo O. Risk factors, diagnosis and prognosis of cervical intraepithelial neoplasia among HIV-infected women. Int J STD AIDS 2008; 19:37-41..

Women living with HIV should be the target population for behavioral interventions, especially in countries with high HIV prevalence. These interventions must be based on a clear understanding of the social and cultural contexts shaping sexual behavior ¹⁸18. Joint United Nations Programme on HIV/AIDS. Social and behaviour change programming. Geneva: Joint United Nations Programme on HIV/AIDS; 2014.. Findings thus suggest that interventions addressing gender-specific issues, power imbalances, and culturally relevant information are more successful in reducing HIV transmission risk behavior among women living with HIV ¹²12. Shuper PA, Kiene SM, Mahlase G, MacDonald S, Christie S, Cornman DH, et al. HIV transmission risk behavior among HIV-positive patients receiving antiretroviral therapy in KwaZulu-Natal, South Africa. AIDS Behav 2014; 18:1532-40.^{), (28}28. Wyatt GE, Longshore D, Chin D, Carmona JV, Loeb TB, Myers HF, et al. The efficacy of an integrated risk reduction intervention for HIV-positive women with child sexual abuse histories. AIDS Behav 2004; 8:453-62.^{), (29}29. Wingood GM, DiClemente RJ, Mikhail I, Lang DL, McCree DH, Davies SL, et al. A randomized controlled trial to reduce HIV transmission risk behaviors and sexually transmitted diseases among women living with HIV: the WiLLOW Program. J Acquir Immune Defic Syndr 2004; 37:S58-67.. Although an emerging body of evidence indicates that behavioral interventions can be effective, few studies have focused on women living with HIV. The absence of solid evidence in this area presents a gap in the field of prevention for this population. A previous meta-analysis investigated the effectiveness of behavioral interventions on promoting condom use among women living with HIV ³⁰30. Carvalho FT, Goncalves TR, Faria ER, Shoveller JA, Piccinini CA, Ramos MC, et al. Behavioral interventions to promote condom use among women living with HIV. Cochrane Database Syst Rev 2011; (9):CD007844.. The pooled analysis of five randomized controlled trials found little effect on behavioral interventions at promoting consistent condom use among HIV-positive women. Since these findings were based on a few small trials, the present study aimed to update and broaden this previous systematic review and meta-analysis ³⁰30. Carvalho FT, Goncalves TR, Faria ER, Shoveller JA, Piccinini CA, Ramos MC, et al. Behavioral interventions to promote condom use among women living with HIV. Cochrane Database Syst Rev 2011; (9):CD007844. in order to better understand the intervention effects on protected sexual behavior in women living with HIV.

Just three years after the original systematic review was performed, several relevant studies were published. Considering the low quality of the evidence found on behavioral interventions to promote condom use among women living with HIV, an update was expected to provide a more accurate picture of these interventions and their implications for public health research and decision-making. Some methodological shortcomings in the initial review could also be addressed (e.g., being based only on a dichotomous outcome, with few studies to conduct subgroup analyses), thereby expanding the findings. Finally, this update review aimed to critically describe and discuss all relevant behavioral interventions to promote condom use among women living with HIV, regardless of whether the study provided data for inclusion in the meta-analysis.

Methods

Since the current study aimed to update a previous review, we replicated the same methodological procedures described in Carvalho et al. ³⁰30. Carvalho FT, Goncalves TR, Faria ER, Shoveller JA, Piccinini CA, Ramos MC, et al. Behavioral interventions to promote condom use among women living with HIV. Cochrane Database Syst Rev 2011; (9):CD007844. and summarized as follows. We searched the following electronic databases regardless of language or publication status using the optimal sensitive search strategy developed by the Cochrane Collaboration ³¹31. Higgins JPT, Green SP. Cochrane handbook for systematic reviews of interventions. Version 5.0.0. Chichester: John Wiley; 2008.: (1) Cochrane Central Register of Controlled Trials (CENTRAL); (2) MEDLINE (PubMed); (3) EMBASE; (4) Latin American and Caribbean Health Sciences Literature (LILACS); (5) PsycInfo; (6) Social Science Citation Index (SocINDEX); and (7) Cumulative Index to Nursing and Allied Health Literature (CINAHL) through EBSCO. The previous search covered the period between January 1980 and May 2010, and this review used specific search terms to identify relevant studies from May 2010 to July 2014. We also examined reference lists from all pertinent reviews and published studies; we searched for unpublished studies in the WHO International Clinical Trials Registry Platform and the Clinicaltrials.gov database and in the International AIDS Conferences, National HIV Prevention Conference (through the Meeting Abstracts Database - NLM Gateway), the International Society for Sexually Transmitted Disease Research, and the Conference on HIV Pathogenesis and Treatment (through the conference websites). Finally, we contacted experts in the field for recommendations on additional intervention research reports and unpublished sources.

A systematic review and meta-analysis were conducted following the Cochrane Collaboration methods ³¹31. Higgins JPT, Green SP. Cochrane handbook for systematic reviews of interventions. Version 5.0.0. Chichester: John Wiley; 2008.. Studies included were randomized trials (RCT) or controlled studies (CCT) investigating HIV or STI behavioral interventions designed for people living with HIV which: (1) included HIV-positive women; (2) focused on condom use promotion; (3) presented outcomes by gender or reported having performed analyses by gender; (4) provided sufficient data to calculate effect sizes (in the meta-analysis portion); and (5) used a 3-month follow-up or more. Interventions could focus on providing information, counseling, health education, emotional well-being, skills training, coping strategies, or peer education related to HIV risk behaviors. There were no restrictions to the intervention's theoretical approach, setting, frequency, or duration. Protected sexual intercourse (or consistent condom use) was described as use of condoms in all vaginal, anal, or oral sexual relations with casual and/or steady partners. All other situations were considered inconsistent condom use (e.g., condom use "almost always" or "sometimes"). This update included a new outcome (reduction in unprotected sexual intercourse - continuous outcome).

The search was completed by one of the authors (T.R.G.). Citations retrieved from electronic searches were inspected by two authors (F.T.C. and E.R.F.) who independently screened studies for inclusion. Uncertainties were resolved by consensus. Following an initial screening, all potentially eligible studies were independently read by at least two authors (E.R.F., F.T.C., or T.R.G.) who assessed in detail the study design, types of participants, types of interventions, and outcome measures. Kappa coefficient indicated good agreement between reviewers both in the first review version (k = 0.76) and in the updated version (k = 0.69).

Using a standardized data extraction form, E.R.F., F.T.C., and T.R.G. extracted the following characteristics from each study that met the inclusion criteria: (1) description of study participants (e.g., sample size, demographic characteristics, country where the study was performed); (2) eligibility criteria for enrolment (e.g., HIV+ diagnosis); (3) details of the intervention (e.g., length of intervention and follow-up, individual or group modality, behavioral techniques); (4) assessment of risk of bias (e.g., study design, generation of allocation sequence, allocation concealment, blinding, loss to follow-up, inclusion of all randomized participants, and incomplete outcome data addressed); (5) outcome measures (e.g., acquisition of STIs or hepatitis B, self-reported protected anal, vaginal, or oral sexual intercourse); and (6) data analysis strategy.

Methodological quality was assessed through RevMan 5 (Cochrane Tech; http://tech.cochrane.org/revman/download) in accordance with the recommendations of the Cochrane Handbook of Systematic Reviews of Interventions³¹31. Higgins JPT, Green SP. Cochrane handbook for systematic reviews of interventions. Version 5.0.0. Chichester: John Wiley; 2008.. Risk of bias was categorized as "low risk", "high risk", or "unclear" and was listed in risk of bias tables separated by trial. We contacted the studies' authors to obtain additional information on missing data. Finally, the GRADE system was used to evaluate the overall quality of evidence for the outcome ³²32. GRADE Working Group. Grading quality of evidence and strength of recommendations. BMJ 2004; 328:1490.^{), (33}33. Guyatt G, Oxman AD, Akl EA, Kunz R, Vist G, Brozek J, et al. GRADE guidelines: 1. Introduction - GRADE evidence profiles and summary of findings tables. J Clin Epidemiol 2011; 64:383-94..

Statistical analysis was conducted according to Cochrane guidelines for systematic reviews of distinct treatments ³¹31. Higgins JPT, Green SP. Cochrane handbook for systematic reviews of interventions. Version 5.0.0. Chichester: John Wiley; 2008.. For dichotomous outcomes (consistent versus inconsistent condom use), the absolute numbers of participants reporting consistent condom use in each group (intervention and control) were extracted. The results for each intervention's effect were expressed as risk ratios (RR) with 95% confidence intervals (95%CI) and were combined for meta-analysis. For the continuous outcome (reduction in unprotected sexual acts), mean and standard deviations of condom use during sexual intercourse (relative frequency) for intervention and control groups were obtained. The difference in means (MD) and respective 95%CI were used to measure the absolute difference between the means in interventions and comparison groups. Since one included study was a cluster randomized trial, we used values of the intra-class correlation coefficient reported in a previous publication related to this intervention ³⁴34. Rotheram-Borus MJ, le Roux IM, Tomlinson M, Mbewu N, Comulada WS, le Roux K, et al. Philani Plus (+): a Mentor Mother community health worker home visiting program to improve maternal and infants' outcomes. Prev Sci 2011; 12:372-88. to adjust trial analysis for clustering and enter its adjusted values in the meta-analysis. Consistent condom use (dichotomous outcome) was estimated using intention-to-treat analysis and included all subjects who were randomized, regardless of baseline condom use behavior. Reduction of unprotected sexual acts (continuous outcome) was estimated through an available case analysis, and the potential impact of missing data on the results was discussed.

The meta-analysis for both dichotomous and continuous outcomes used random-effects model in the RevMan 5.3 software. This strategy accounts for potential heterogeneity following unique intervention approaches developed in diverse study settings. Statistical heterogeneity between results of different studies was examined with the χ² test. A p-value for a χ² test of less than 0.10 indicated heterogeneity. An alternative approach to quantify the effect of heterogeneity is assessing the inconsistency (I²) among the results of studies with 95% uncertainty intervals. A value of 0% indicates no observed heterogeneity, and a value greater than 50% indicates substantial heterogeneity. Reporting bias was assessed by examining a funnel plot graph, which can detect small trial effects, even those resulting from publication bias.

The protocol for the first systematic review was planned to conduct subgroup analyses in order to explore possible sources of heterogeneity, but which were not performed because few studies were included. In the update, subgroup analyses were feasible for the dichotomous outcome (e.g., consistent condom use). We performed such analyses taking into account interventions that exclusively targeted (versus did not exclusively target) women living with HIV, and another considering the countries where the studies were done (North America versus Africa).

Results

In the first comprehensive search for this review ³⁰30. Carvalho FT, Goncalves TR, Faria ER, Shoveller JA, Piccinini CA, Ramos MC, et al. Behavioral interventions to promote condom use among women living with HIV. Cochrane Database Syst Rev 2011; (9):CD007844., out of 3,046 citations, 35 potentially relevant studies and their full-text versions were extracted. The search in the update was performed in July 2014 and retrieved 1,721 citations. Thirty-four intervention studies were selected for full-text review in the update, including 24 articles, 6 conference proceedings, and 4 registered trials. For the sake of comprehensiveness, we reported the results of the selection process just to the period from 2010 to 2014, when 3 new studies were included in the meta-analysis. The flowchart in Figure 1 summarizes the study selection process. The quantitative syntheses jointly describe the results from studies included in the first version (5 studies) and in the update (3 studies). Likewise, the qualitative syntheses comprised 13 studies (5 from the first version plus 8 added in the update).

Included studies

Data from 8 RCT with a total of 1,355 women living with HIV were included in the meta-analyses. Of these, 5 were conducted in the United States ²⁹29. Wingood GM, DiClemente RJ, Mikhail I, Lang DL, McCree DH, Davies SL, et al. A randomized controlled trial to reduce HIV transmission risk behaviors and sexually transmitted diseases among women living with HIV: the WiLLOW Program. J Acquir Immune Defic Syndr 2004; 37:S58-67.^{), (35}35. Gilbert P, Ciccarone D, Gansky SA, Bangsberg DR, Clanon K, McPhee SJ, et al. Interactive "Video Doctor" counseling reduces drug and sexual risk behaviors among HIV-positive patients in diverse outpatient settings. PLoS One 2008; 3:e1988.^{), (36}36. Sikkema KJ, Wilson PA, Hansen NB, Kochman A, Neufeld S, Ghebremichael MS, et al. Effects of a coping intervention on transmission risk behavior among people living with HIV/AIDS and a history of childhood sexual abuse. J Acquir Immune Defic Syndr 2008; 47:506-13.^{), (37}37. DeMarco RF, Chan K. The Sistah Powah structured writing intervention: a feasibility study for aging, low-income, HIV-positive black women. Am J Health Promot 2013; 28:108-18.^{), (38}38. Holstad MM, DiIorio C, Kelley ME, Resnicow K, Sharma S. Group motivational interviewing to promote adherence to antiretroviral medications and risk reduction behaviors in HIV infected women. AIDS Behav 2011; 15:885-96. and 3 in South Africa ³⁹39. Cornman DH, Kiene SM, Christie S, Fisher WA, Shuper PA, Pillay S, et al. Clinic-based intervention reduces unprotected sexual behavior among HIV-infected patients in KwaZulu-Natal, South Africa: results of a pilot study. J Acquir Immune Defic Syndr 2008; 48:553-60.^{), (40}40. Le Roux IM, Tomlinson M, Harwood JM, O'Connor MJ, Worthman CM, Mbewu N, et al. Outcomes of home visits for pregnant mothers and their infants: a cluster randomized controlled trial. AIDS 2013; 27:1461-71.^{), (41}41. Saleh-Onoya D, Reddy PS, Ruiter RA, Sifunda S, Wingood G, van den Borne B. Condom use promotion among isiXhosa speaking women living with HIV in the Western Cape Province, South Africa: a pilot study. AIDS Care 2009; 21:817-25.. Five interventions were developed exclusively for women living with HIV ²⁹29. Wingood GM, DiClemente RJ, Mikhail I, Lang DL, McCree DH, Davies SL, et al. A randomized controlled trial to reduce HIV transmission risk behaviors and sexually transmitted diseases among women living with HIV: the WiLLOW Program. J Acquir Immune Defic Syndr 2004; 37:S58-67.^{), (37}37. DeMarco RF, Chan K. The Sistah Powah structured writing intervention: a feasibility study for aging, low-income, HIV-positive black women. Am J Health Promot 2013; 28:108-18.^{), (38}38. Holstad MM, DiIorio C, Kelley ME, Resnicow K, Sharma S. Group motivational interviewing to promote adherence to antiretroviral medications and risk reduction behaviors in HIV infected women. AIDS Behav 2011; 15:885-96.^{), (40}40. Le Roux IM, Tomlinson M, Harwood JM, O'Connor MJ, Worthman CM, Mbewu N, et al. Outcomes of home visits for pregnant mothers and their infants: a cluster randomized controlled trial. AIDS 2013; 27:1461-71.^{), (41}41. Saleh-Onoya D, Reddy PS, Ruiter RA, Sifunda S, Wingood G, van den Borne B. Condom use promotion among isiXhosa speaking women living with HIV in the Western Cape Province, South Africa: a pilot study. AIDS Care 2009; 21:817-25. and 3 targeted both women and men living with HIV ³⁵35. Gilbert P, Ciccarone D, Gansky SA, Bangsberg DR, Clanon K, McPhee SJ, et al. Interactive "Video Doctor" counseling reduces drug and sexual risk behaviors among HIV-positive patients in diverse outpatient settings. PLoS One 2008; 3:e1988.^{), (36}36. Sikkema KJ, Wilson PA, Hansen NB, Kochman A, Neufeld S, Ghebremichael MS, et al. Effects of a coping intervention on transmission risk behavior among people living with HIV/AIDS and a history of childhood sexual abuse. J Acquir Immune Defic Syndr 2008; 47:506-13.^{), (39}39. Cornman DH, Kiene SM, Christie S, Fisher WA, Shuper PA, Pillay S, et al. Clinic-based intervention reduces unprotected sexual behavior among HIV-infected patients in KwaZulu-Natal, South Africa: results of a pilot study. J Acquir Immune Defic Syndr 2008; 48:553-60.. None targeted couples or participants' sex partners. One intervention was developed for pregnant women in sub-Saharan African communities including those living with HIV ⁴⁰40. Le Roux IM, Tomlinson M, Harwood JM, O'Connor MJ, Worthman CM, Mbewu N, et al. Outcomes of home visits for pregnant mothers and their infants: a cluster randomized controlled trial. AIDS 2013; 27:1461-71.. All interventions followed the initiation of ART.

Even after contact with authors by e-mail, another 3 studies that met the inclusion criteria could not be included in the meta-analysis, since no further information was obtained about either the absolute number of women living with HIV engaged in safe sex or the mean and standard deviation of protected sexual acts ⁴²42. Echenique M, Illa L, Saint-Jean G, Avellaneda VB, Sanchez-Martinez M, Eisdorfer C. Impact of a secondary prevention intervention among HIV-positive older women. AIDS Care 2013; 25:443-6.^{), (43}43. Jones DL, Weiss SM, Malow R, Ishii M, Devieux J, Stanley H, et al. A brief sexual barrier intervention for women living with AIDS: acceptability, use, and ethnicity. J Urban Health 2001; 78:593-604.^{), (44}44. Teti M, Bowleg L, Cole R, Lloyd L, Rubinstein S, Spencer S, et al. A mixed methods evaluation of the effect of the Protect and Respect intervention on the condom use and disclosure practices of women living with HIV/AIDS. AIDS Behav 2010; 14:567-79., besides another study due to lack of further information on analyses done on intervention effects by gender ⁴⁵45. Kalichman SC, Rompa D, Cage M, DiFonzo K, Simpson D, Austin J, et al. Effectiveness of an intervention to reduce HIV transmission risks in HIV-positive people. Am J Prev Med 2001; 21:84-92.. We identified only 1 non-randomized study ⁴⁶46. Fisher JD, Fisher WA, Cornman DH, Amico RK, Bryan A, Friedland GH. Clinician-delivered intervention during routine clinical care reduces unprotected sexual behavior among HIV-infected patients. J Acquir Immune Defic Syndr 2006; 41:44-52. which provided complete data on female participants, which was not included in the meta-analysis to avoid potential confounding. We decided to include the 5 interventions in the systematic review and describe the results reported narratively by the authors. All 5 studies were developed in the United States, and 3 involved interventions targeting women living with HIV ⁴²42. Echenique M, Illa L, Saint-Jean G, Avellaneda VB, Sanchez-Martinez M, Eisdorfer C. Impact of a secondary prevention intervention among HIV-positive older women. AIDS Care 2013; 25:443-6.^{), (43}43. Jones DL, Weiss SM, Malow R, Ishii M, Devieux J, Stanley H, et al. A brief sexual barrier intervention for women living with AIDS: acceptability, use, and ethnicity. J Urban Health 2001; 78:593-604.^{), (44}44. Teti M, Bowleg L, Cole R, Lloyd L, Rubinstein S, Spencer S, et al. A mixed methods evaluation of the effect of the Protect and Respect intervention on the condom use and disclosure practices of women living with HIV/AIDS. AIDS Behav 2010; 14:567-79.. Kalichman et al. ⁴⁵45. Kalichman SC, Rompa D, Cage M, DiFonzo K, Simpson D, Austin J, et al. Effectiveness of an intervention to reduce HIV transmission risks in HIV-positive people. Am J Prev Med 2001; 21:84-92. conducted interventions for women and men living with HIV separately, and Fisher et al. ⁴⁶46. Fisher JD, Fisher WA, Cornman DH, Amico RK, Bryan A, Friedland GH. Clinician-delivered intervention during routine clinical care reduces unprotected sexual behavior among HIV-infected patients. J Acquir Immune Defic Syndr 2006; 41:44-52. included both female and male participants in the intervention or comparison groups.

Considering the 13 studies included in the systematic review, most involved group-level interventions ²⁹29. Wingood GM, DiClemente RJ, Mikhail I, Lang DL, McCree DH, Davies SL, et al. A randomized controlled trial to reduce HIV transmission risk behaviors and sexually transmitted diseases among women living with HIV: the WiLLOW Program. J Acquir Immune Defic Syndr 2004; 37:S58-67.^{), (36}36. Sikkema KJ, Wilson PA, Hansen NB, Kochman A, Neufeld S, Ghebremichael MS, et al. Effects of a coping intervention on transmission risk behavior among people living with HIV/AIDS and a history of childhood sexual abuse. J Acquir Immune Defic Syndr 2008; 47:506-13.^{), (37}37. DeMarco RF, Chan K. The Sistah Powah structured writing intervention: a feasibility study for aging, low-income, HIV-positive black women. Am J Health Promot 2013; 28:108-18.^{), (38}38. Holstad MM, DiIorio C, Kelley ME, Resnicow K, Sharma S. Group motivational interviewing to promote adherence to antiretroviral medications and risk reduction behaviors in HIV infected women. AIDS Behav 2011; 15:885-96.^{), (41}41. Saleh-Onoya D, Reddy PS, Ruiter RA, Sifunda S, Wingood G, van den Borne B. Condom use promotion among isiXhosa speaking women living with HIV in the Western Cape Province, South Africa: a pilot study. AIDS Care 2009; 21:817-25.^{), (42}42. Echenique M, Illa L, Saint-Jean G, Avellaneda VB, Sanchez-Martinez M, Eisdorfer C. Impact of a secondary prevention intervention among HIV-positive older women. AIDS Care 2013; 25:443-6.^{), (43}43. Jones DL, Weiss SM, Malow R, Ishii M, Devieux J, Stanley H, et al. A brief sexual barrier intervention for women living with AIDS: acceptability, use, and ethnicity. J Urban Health 2001; 78:593-604.^{), (44}44. Teti M, Bowleg L, Cole R, Lloyd L, Rubinstein S, Spencer S, et al. A mixed methods evaluation of the effect of the Protect and Respect intervention on the condom use and disclosure practices of women living with HIV/AIDS. AIDS Behav 2010; 14:567-79.^{), (45}45. Kalichman SC, Rompa D, Cage M, DiFonzo K, Simpson D, Austin J, et al. Effectiveness of an intervention to reduce HIV transmission risks in HIV-positive people. Am J Prev Med 2001; 21:84-92. and were delivered in settings for HIV care ²⁹29. Wingood GM, DiClemente RJ, Mikhail I, Lang DL, McCree DH, Davies SL, et al. A randomized controlled trial to reduce HIV transmission risk behaviors and sexually transmitted diseases among women living with HIV: the WiLLOW Program. J Acquir Immune Defic Syndr 2004; 37:S58-67.^{), (35}35. Gilbert P, Ciccarone D, Gansky SA, Bangsberg DR, Clanon K, McPhee SJ, et al. Interactive "Video Doctor" counseling reduces drug and sexual risk behaviors among HIV-positive patients in diverse outpatient settings. PLoS One 2008; 3:e1988.^{), (38}38. Holstad MM, DiIorio C, Kelley ME, Resnicow K, Sharma S. Group motivational interviewing to promote adherence to antiretroviral medications and risk reduction behaviors in HIV infected women. AIDS Behav 2011; 15:885-96.^{), (39}39. Cornman DH, Kiene SM, Christie S, Fisher WA, Shuper PA, Pillay S, et al. Clinic-based intervention reduces unprotected sexual behavior among HIV-infected patients in KwaZulu-Natal, South Africa: results of a pilot study. J Acquir Immune Defic Syndr 2008; 48:553-60.^{), (42}42. Echenique M, Illa L, Saint-Jean G, Avellaneda VB, Sanchez-Martinez M, Eisdorfer C. Impact of a secondary prevention intervention among HIV-positive older women. AIDS Care 2013; 25:443-6.^{), (43}43. Jones DL, Weiss SM, Malow R, Ishii M, Devieux J, Stanley H, et al. A brief sexual barrier intervention for women living with AIDS: acceptability, use, and ethnicity. J Urban Health 2001; 78:593-604.^{), (44}44. Teti M, Bowleg L, Cole R, Lloyd L, Rubinstein S, Spencer S, et al. A mixed methods evaluation of the effect of the Protect and Respect intervention on the condom use and disclosure practices of women living with HIV/AIDS. AIDS Behav 2010; 14:567-79.^{), (45}45. Kalichman SC, Rompa D, Cage M, DiFonzo K, Simpson D, Austin J, et al. Effectiveness of an intervention to reduce HIV transmission risks in HIV-positive people. Am J Prev Med 2001; 21:84-92.^{), (46}46. Fisher JD, Fisher WA, Cornman DH, Amico RK, Bryan A, Friedland GH. Clinician-delivered intervention during routine clinical care reduces unprotected sexual behavior among HIV-infected patients. J Acquir Immune Defic Syndr 2006; 41:44-52.. One was home-based ⁴⁰40. Le Roux IM, Tomlinson M, Harwood JM, O'Connor MJ, Worthman CM, Mbewu N, et al. Outcomes of home visits for pregnant mothers and their infants: a cluster randomized controlled trial. AIDS 2013; 27:1461-71. and another 3 were developed in community settings ^36,37,41. The intervention facilitators were only health workers in 6 interventions ³⁶36. Sikkema KJ, Wilson PA, Hansen NB, Kochman A, Neufeld S, Ghebremichael MS, et al. Effects of a coping intervention on transmission risk behavior among people living with HIV/AIDS and a history of childhood sexual abuse. J Acquir Immune Defic Syndr 2008; 47:506-13.^{), (38}38. Holstad MM, DiIorio C, Kelley ME, Resnicow K, Sharma S. Group motivational interviewing to promote adherence to antiretroviral medications and risk reduction behaviors in HIV infected women. AIDS Behav 2011; 15:885-96.^{), (39}39. Cornman DH, Kiene SM, Christie S, Fisher WA, Shuper PA, Pillay S, et al. Clinic-based intervention reduces unprotected sexual behavior among HIV-infected patients in KwaZulu-Natal, South Africa: results of a pilot study. J Acquir Immune Defic Syndr 2008; 48:553-60.^{), (40}40. Le Roux IM, Tomlinson M, Harwood JM, O'Connor MJ, Worthman CM, Mbewu N, et al. Outcomes of home visits for pregnant mothers and their infants: a cluster randomized controlled trial. AIDS 2013; 27:1461-71.^{), (43}43. Jones DL, Weiss SM, Malow R, Ishii M, Devieux J, Stanley H, et al. A brief sexual barrier intervention for women living with AIDS: acceptability, use, and ethnicity. J Urban Health 2001; 78:593-604.^{), (46}46. Fisher JD, Fisher WA, Cornman DH, Amico RK, Bryan A, Friedland GH. Clinician-delivered intervention during routine clinical care reduces unprotected sexual behavior among HIV-infected patients. J Acquir Immune Defic Syndr 2006; 41:44-52., health workers plus peer leaders in 4 interventions ²⁹29. Wingood GM, DiClemente RJ, Mikhail I, Lang DL, McCree DH, Davies SL, et al. A randomized controlled trial to reduce HIV transmission risk behaviors and sexually transmitted diseases among women living with HIV: the WiLLOW Program. J Acquir Immune Defic Syndr 2004; 37:S58-67.^{), (41}41. Saleh-Onoya D, Reddy PS, Ruiter RA, Sifunda S, Wingood G, van den Borne B. Condom use promotion among isiXhosa speaking women living with HIV in the Western Cape Province, South Africa: a pilot study. AIDS Care 2009; 21:817-25.^{), (44}44. Teti M, Bowleg L, Cole R, Lloyd L, Rubinstein S, Spencer S, et al. A mixed methods evaluation of the effect of the Protect and Respect intervention on the condom use and disclosure practices of women living with HIV/AIDS. AIDS Behav 2010; 14:567-79.^{), (45}45. Kalichman SC, Rompa D, Cage M, DiFonzo K, Simpson D, Austin J, et al. Effectiveness of an intervention to reduce HIV transmission risks in HIV-positive people. Am J Prev Med 2001; 21:84-92., and only peer leaders in 1 intervention ³⁷37. DeMarco RF, Chan K. The Sistah Powah structured writing intervention: a feasibility study for aging, low-income, HIV-positive black women. Am J Health Promot 2013; 28:108-18.. One intervention was computer-delivered ³⁵35. Gilbert P, Ciccarone D, Gansky SA, Bangsberg DR, Clanon K, McPhee SJ, et al. Interactive "Video Doctor" counseling reduces drug and sexual risk behaviors among HIV-positive patients in diverse outpatient settings. PLoS One 2008; 3:e1988. and another failed to report this information ⁴²42. Echenique M, Illa L, Saint-Jean G, Avellaneda VB, Sanchez-Martinez M, Eisdorfer C. Impact of a secondary prevention intervention among HIV-positive older women. AIDS Care 2013; 25:443-6..

All interventions followed standardized procedures. Principles of cognitive-behavioral theory guided almost all of the interventions, focusing on motivational interview, stress management and coping strategies, and psycho-educational techniques. One intervention ³⁷37. DeMarco RF, Chan K. The Sistah Powah structured writing intervention: a feasibility study for aging, low-income, HIV-positive black women. Am J Health Promot 2013; 28:108-18. involved narrative strategies and social support, and 4 added components of gender and power theories ²⁹29. Wingood GM, DiClemente RJ, Mikhail I, Lang DL, McCree DH, Davies SL, et al. A randomized controlled trial to reduce HIV transmission risk behaviors and sexually transmitted diseases among women living with HIV: the WiLLOW Program. J Acquir Immune Defic Syndr 2004; 37:S58-67.^{), (37}37. DeMarco RF, Chan K. The Sistah Powah structured writing intervention: a feasibility study for aging, low-income, HIV-positive black women. Am J Health Promot 2013; 28:108-18.^{), (41}41. Saleh-Onoya D, Reddy PS, Ruiter RA, Sifunda S, Wingood G, van den Borne B. Condom use promotion among isiXhosa speaking women living with HIV in the Western Cape Province, South Africa: a pilot study. AIDS Care 2009; 21:817-25.^{), (44}44. Teti M, Bowleg L, Cole R, Lloyd L, Rubinstein S, Spencer S, et al. A mixed methods evaluation of the effect of the Protect and Respect intervention on the condom use and disclosure practices of women living with HIV/AIDS. AIDS Behav 2010; 14:567-79.. Only 6 studies explicitly mentioned that gender issues were included in the interventions ²⁹29. Wingood GM, DiClemente RJ, Mikhail I, Lang DL, McCree DH, Davies SL, et al. A randomized controlled trial to reduce HIV transmission risk behaviors and sexually transmitted diseases among women living with HIV: the WiLLOW Program. J Acquir Immune Defic Syndr 2004; 37:S58-67.^{), (37}37. DeMarco RF, Chan K. The Sistah Powah structured writing intervention: a feasibility study for aging, low-income, HIV-positive black women. Am J Health Promot 2013; 28:108-18.^{), (38}38. Holstad MM, DiIorio C, Kelley ME, Resnicow K, Sharma S. Group motivational interviewing to promote adherence to antiretroviral medications and risk reduction behaviors in HIV infected women. AIDS Behav 2011; 15:885-96.^{), (41}41. Saleh-Onoya D, Reddy PS, Ruiter RA, Sifunda S, Wingood G, van den Borne B. Condom use promotion among isiXhosa speaking women living with HIV in the Western Cape Province, South Africa: a pilot study. AIDS Care 2009; 21:817-25.^{), (43}43. Jones DL, Weiss SM, Malow R, Ishii M, Devieux J, Stanley H, et al. A brief sexual barrier intervention for women living with AIDS: acceptability, use, and ethnicity. J Urban Health 2001; 78:593-604.^{), (44}44. Teti M, Bowleg L, Cole R, Lloyd L, Rubinstein S, Spencer S, et al. A mixed methods evaluation of the effect of the Protect and Respect intervention on the condom use and disclosure practices of women living with HIV/AIDS. AIDS Behav 2010; 14:567-79.. Eight interventions focused primarily on changing sexual risk behavior and secondarily included such issues as HIV status disclosure, health care, and social support ²⁹29. Wingood GM, DiClemente RJ, Mikhail I, Lang DL, McCree DH, Davies SL, et al. A randomized controlled trial to reduce HIV transmission risk behaviors and sexually transmitted diseases among women living with HIV: the WiLLOW Program. J Acquir Immune Defic Syndr 2004; 37:S58-67.^{), (37}37. DeMarco RF, Chan K. The Sistah Powah structured writing intervention: a feasibility study for aging, low-income, HIV-positive black women. Am J Health Promot 2013; 28:108-18.^{), (39}39. Cornman DH, Kiene SM, Christie S, Fisher WA, Shuper PA, Pillay S, et al. Clinic-based intervention reduces unprotected sexual behavior among HIV-infected patients in KwaZulu-Natal, South Africa: results of a pilot study. J Acquir Immune Defic Syndr 2008; 48:553-60.^{), (41}41. Saleh-Onoya D, Reddy PS, Ruiter RA, Sifunda S, Wingood G, van den Borne B. Condom use promotion among isiXhosa speaking women living with HIV in the Western Cape Province, South Africa: a pilot study. AIDS Care 2009; 21:817-25.^{), (42}42. Echenique M, Illa L, Saint-Jean G, Avellaneda VB, Sanchez-Martinez M, Eisdorfer C. Impact of a secondary prevention intervention among HIV-positive older women. AIDS Care 2013; 25:443-6.^{), (43}43. Jones DL, Weiss SM, Malow R, Ishii M, Devieux J, Stanley H, et al. A brief sexual barrier intervention for women living with AIDS: acceptability, use, and ethnicity. J Urban Health 2001; 78:593-604.^{), (44}44. Teti M, Bowleg L, Cole R, Lloyd L, Rubinstein S, Spencer S, et al. A mixed methods evaluation of the effect of the Protect and Respect intervention on the condom use and disclosure practices of women living with HIV/AIDS. AIDS Behav 2010; 14:567-79.^{), (45}45. Kalichman SC, Rompa D, Cage M, DiFonzo K, Simpson D, Austin J, et al. Effectiveness of an intervention to reduce HIV transmission risks in HIV-positive people. Am J Prev Med 2001; 21:84-92.. Four interventions also encompassed drug use ³⁵35. Gilbert P, Ciccarone D, Gansky SA, Bangsberg DR, Clanon K, McPhee SJ, et al. Interactive "Video Doctor" counseling reduces drug and sexual risk behaviors among HIV-positive patients in diverse outpatient settings. PLoS One 2008; 3:e1988.^{), (38}38. Holstad MM, DiIorio C, Kelley ME, Resnicow K, Sharma S. Group motivational interviewing to promote adherence to antiretroviral medications and risk reduction behaviors in HIV infected women. AIDS Behav 2011; 15:885-96.^{), (40}40. Le Roux IM, Tomlinson M, Harwood JM, O'Connor MJ, Worthman CM, Mbewu N, et al. Outcomes of home visits for pregnant mothers and their infants: a cluster randomized controlled trial. AIDS 2013; 27:1461-71.^{), (46}46. Fisher JD, Fisher WA, Cornman DH, Amico RK, Bryan A, Friedland GH. Clinician-delivered intervention during routine clinical care reduces unprotected sexual behavior among HIV-infected patients. J Acquir Immune Defic Syndr 2006; 41:44-52. and another covered mental health issues ³⁶36. Sikkema KJ, Wilson PA, Hansen NB, Kochman A, Neufeld S, Ghebremichael MS, et al. Effects of a coping intervention on transmission risk behavior among people living with HIV/AIDS and a history of childhood sexual abuse. J Acquir Immune Defic Syndr 2008; 47:506-13.. Beyond sexual risk behavior, 1 intervention targeted infant growth and nutrition, breastfeeding, and medical adherence ⁴⁰40. Le Roux IM, Tomlinson M, Harwood JM, O'Connor MJ, Worthman CM, Mbewu N, et al. Outcomes of home visits for pregnant mothers and their infants: a cluster randomized controlled trial. AIDS 2013; 27:1461-71., while another aimed to improve adherence to antiretroviral therapy ³⁸38. Holstad MM, DiIorio C, Kelley ME, Resnicow K, Sharma S. Group motivational interviewing to promote adherence to antiretroviral medications and risk reduction behaviors in HIV infected women. AIDS Behav 2011; 15:885-96.. Regarding total time of exposure to interventions, in 3 studies it was less than three hours ³⁵35. Gilbert P, Ciccarone D, Gansky SA, Bangsberg DR, Clanon K, McPhee SJ, et al. Interactive "Video Doctor" counseling reduces drug and sexual risk behaviors among HIV-positive patients in diverse outpatient settings. PLoS One 2008; 3:e1988.^{), (39}39. Cornman DH, Kiene SM, Christie S, Fisher WA, Shuper PA, Pillay S, et al. Clinic-based intervention reduces unprotected sexual behavior among HIV-infected patients in KwaZulu-Natal, South Africa: results of a pilot study. J Acquir Immune Defic Syndr 2008; 48:553-60.^{), (46}46. Fisher JD, Fisher WA, Cornman DH, Amico RK, Bryan A, Friedland GH. Clinician-delivered intervention during routine clinical care reduces unprotected sexual behavior among HIV-infected patients. J Acquir Immune Defic Syndr 2006; 41:44-52., in 6 it ranged from 5 to 10 hours ³⁷37. DeMarco RF, Chan K. The Sistah Powah structured writing intervention: a feasibility study for aging, low-income, HIV-positive black women. Am J Health Promot 2013; 28:108-18.^{), (40}40. Le Roux IM, Tomlinson M, Harwood JM, O'Connor MJ, Worthman CM, Mbewu N, et al. Outcomes of home visits for pregnant mothers and their infants: a cluster randomized controlled trial. AIDS 2013; 27:1461-71.^{), (42}42. Echenique M, Illa L, Saint-Jean G, Avellaneda VB, Sanchez-Martinez M, Eisdorfer C. Impact of a secondary prevention intervention among HIV-positive older women. AIDS Care 2013; 25:443-6.^{), (43}43. Jones DL, Weiss SM, Malow R, Ishii M, Devieux J, Stanley H, et al. A brief sexual barrier intervention for women living with AIDS: acceptability, use, and ethnicity. J Urban Health 2001; 78:593-604.^{), (44}44. Teti M, Bowleg L, Cole R, Lloyd L, Rubinstein S, Spencer S, et al. A mixed methods evaluation of the effect of the Protect and Respect intervention on the condom use and disclosure practices of women living with HIV/AIDS. AIDS Behav 2010; 14:567-79.^{), (45}45. Kalichman SC, Rompa D, Cage M, DiFonzo K, Simpson D, Austin J, et al. Effectiveness of an intervention to reduce HIV transmission risks in HIV-positive people. Am J Prev Med 2001; 21:84-92., in another 3 it ranged from 13 to 16 hours ²⁹29. Wingood GM, DiClemente RJ, Mikhail I, Lang DL, McCree DH, Davies SL, et al. A randomized controlled trial to reduce HIV transmission risk behaviors and sexually transmitted diseases among women living with HIV: the WiLLOW Program. J Acquir Immune Defic Syndr 2004; 37:S58-67.^{), (38}38. Holstad MM, DiIorio C, Kelley ME, Resnicow K, Sharma S. Group motivational interviewing to promote adherence to antiretroviral medications and risk reduction behaviors in HIV infected women. AIDS Behav 2011; 15:885-96.^{), (41}41. Saleh-Onoya D, Reddy PS, Ruiter RA, Sifunda S, Wingood G, van den Borne B. Condom use promotion among isiXhosa speaking women living with HIV in the Western Cape Province, South Africa: a pilot study. AIDS Care 2009; 21:817-25., and in 1 study exposure lasted 22 hours and a half ³⁶36. Sikkema KJ, Wilson PA, Hansen NB, Kochman A, Neufeld S, Ghebremichael MS, et al. Effects of a coping intervention on transmission risk behavior among people living with HIV/AIDS and a history of childhood sexual abuse. J Acquir Immune Defic Syndr 2008; 47:506-13..

Table 1 shows details on methodology, participants, interventions, and outcomes for each included study.

Excluded studies

After assessment, 27 studies were excluded: 5 did not consider gender in their outcome analyses; 5 included strategies to promote condom use in control groups; 4 were not RCT or CCT studies; 4 included non-HIV-infected participants; 2 did not determine the study population's HIV status; 1 did not assess the target outcomes; 1 intervention did not aim to promote condom use; and 1 only presented results for couples. Another 4 studies were ongoing trials ⁴⁷47. Kalichman SC. Behavioral intervention to enhance HIV test/treat. https://clinicaltrials.gov/ct2/show/NCT01752777 (accessed on 24/Nov/2016).
https://clinicaltrials.gov/ct2/show/NCT0... ^{), (48}48. Kidder DP, Bachanas P, Medley A, Pals S, Nuwagaba-Biribonwoha H, Ackers M, et al. HIV prevention in care and treatment settings: baseline risk behaviors among HIV patients in Kenya, Namibia, and Tanzania. PLoS One 2013; 8:e57215.^{), (49}49. Wilson MM, Frimpong S, McLaughlin G, Hilliard A, Seaman L, Mitchell-Samon LM, et al. The Interdiction Project (TIP) phase I-III: a potential innovation program for HIV-positive persons to reduce STD co-infection with HIV/AIDS, new HIV infection and resistant HIV transmission. In: 19th International AIDS Conference. http://www.abstract-archive.org/.
http://www.abstract-archive.org/... ^{), (50}50. Guo Y, Su B. A research report on "positive prevention" intervention in two ethnic habitats along the border with Myanmar in Yunnan. Retrovirology 2010; 7:P96. and may be eligible when the results become available.

Risk of bias in included studies

There was limited evidence of selection bias, selective reporting, and other biases across all the studies. It was not possible to clearly define the method used in random sequence generation ⁴²42. Echenique M, Illa L, Saint-Jean G, Avellaneda VB, Sanchez-Martinez M, Eisdorfer C. Impact of a secondary prevention intervention among HIV-positive older women. AIDS Care 2013; 25:443-6.^{), (45}45. Kalichman SC, Rompa D, Cage M, DiFonzo K, Simpson D, Austin J, et al. Effectiveness of an intervention to reduce HIV transmission risks in HIV-positive people. Am J Prev Med 2001; 21:84-92. or the allocation concealment strategy ³⁷37. DeMarco RF, Chan K. The Sistah Powah structured writing intervention: a feasibility study for aging, low-income, HIV-positive black women. Am J Health Promot 2013; 28:108-18.^{), (42}42. Echenique M, Illa L, Saint-Jean G, Avellaneda VB, Sanchez-Martinez M, Eisdorfer C. Impact of a secondary prevention intervention among HIV-positive older women. AIDS Care 2013; 25:443-6. used in three of the studies, while another two studies used quasi-experimental designs ⁴³43. Jones DL, Weiss SM, Malow R, Ishii M, Devieux J, Stanley H, et al. A brief sexual barrier intervention for women living with AIDS: acceptability, use, and ethnicity. J Urban Health 2001; 78:593-604.^{), (46}46. Fisher JD, Fisher WA, Cornman DH, Amico RK, Bryan A, Friedland GH. Clinician-delivered intervention during routine clinical care reduces unprotected sexual behavior among HIV-infected patients. J Acquir Immune Defic Syndr 2006; 41:44-52.. All authors who were contacted responded with explanations for participants' dropout. Four studies did not report attrition ³⁷37. DeMarco RF, Chan K. The Sistah Powah structured writing intervention: a feasibility study for aging, low-income, HIV-positive black women. Am J Health Promot 2013; 28:108-18.^{), (41}41. Saleh-Onoya D, Reddy PS, Ruiter RA, Sifunda S, Wingood G, van den Borne B. Condom use promotion among isiXhosa speaking women living with HIV in the Western Cape Province, South Africa: a pilot study. AIDS Care 2009; 21:817-25.^{), (42}42. Echenique M, Illa L, Saint-Jean G, Avellaneda VB, Sanchez-Martinez M, Eisdorfer C. Impact of a secondary prevention intervention among HIV-positive older women. AIDS Care 2013; 25:443-6.^{), (43}43. Jones DL, Weiss SM, Malow R, Ishii M, Devieux J, Stanley H, et al. A brief sexual barrier intervention for women living with AIDS: acceptability, use, and ethnicity. J Urban Health 2001; 78:593-604., however, authors of 2 studies included in the meta-analysis did describe the absolute number of participants for each target outcome ³⁷37. DeMarco RF, Chan K. The Sistah Powah structured writing intervention: a feasibility study for aging, low-income, HIV-positive black women. Am J Health Promot 2013; 28:108-18.^{), (41}41. Saleh-Onoya D, Reddy PS, Ruiter RA, Sifunda S, Wingood G, van den Borne B. Condom use promotion among isiXhosa speaking women living with HIV in the Western Cape Province, South Africa: a pilot study. AIDS Care 2009; 21:817-25.. Regarding loss to follow-up, the following studies found higher percentages of female participants dropping out before the last assessment, considering both control and intervention groups: Sikkema et al. ³⁶36. Sikkema KJ, Wilson PA, Hansen NB, Kochman A, Neufeld S, Ghebremichael MS, et al. Effects of a coping intervention on transmission risk behavior among people living with HIV/AIDS and a history of childhood sexual abuse. J Acquir Immune Defic Syndr 2008; 47:506-13. (41%); Gilbert et al. ³⁵35. Gilbert P, Ciccarone D, Gansky SA, Bangsberg DR, Clanon K, McPhee SJ, et al. Interactive "Video Doctor" counseling reduces drug and sexual risk behaviors among HIV-positive patients in diverse outpatient settings. PLoS One 2008; 3:e1988. (28.5%), and Saleh-Onoya et al. ⁴¹41. Saleh-Onoya D, Reddy PS, Ruiter RA, Sifunda S, Wingood G, van den Borne B. Condom use promotion among isiXhosa speaking women living with HIV in the Western Cape Province, South Africa: a pilot study. AIDS Care 2009; 21:817-25. (24.5%). The remaining studies had 15% loss to follow-up or less.

Most studies performed intent-to-treat analysis, but 3 of the included studies ³⁷37. DeMarco RF, Chan K. The Sistah Powah structured writing intervention: a feasibility study for aging, low-income, HIV-positive black women. Am J Health Promot 2013; 28:108-18.^{), (41}41. Saleh-Onoya D, Reddy PS, Ruiter RA, Sifunda S, Wingood G, van den Borne B. Condom use promotion among isiXhosa speaking women living with HIV in the Western Cape Province, South Africa: a pilot study. AIDS Care 2009; 21:817-25.^{), (42}42. Echenique M, Illa L, Saint-Jean G, Avellaneda VB, Sanchez-Martinez M, Eisdorfer C. Impact of a secondary prevention intervention among HIV-positive older women. AIDS Care 2013; 25:443-6. and 1 that was not included ⁴³43. Jones DL, Weiss SM, Malow R, Ishii M, Devieux J, Stanley H, et al. A brief sexual barrier intervention for women living with AIDS: acceptability, use, and ethnicity. J Urban Health 2001; 78:593-604. in the meta-analysis did not perform it. It was not possible to determine whether intent-to-treat analysis was used in another study ⁴⁰40. Le Roux IM, Tomlinson M, Harwood JM, O'Connor MJ, Worthman CM, Mbewu N, et al. Outcomes of home visits for pregnant mothers and their infants: a cluster randomized controlled trial. AIDS 2013; 27:1461-71.. Figure 2 summarizes reviewers' assessment of the studies' methodological qualities.

Quality of the evidence

We performed a GRADE evaluation of the quality of evidence for all interventions included in this meta-analysis ³²32. GRADE Working Group. Grading quality of evidence and strength of recommendations. BMJ 2004; 328:1490.^{), (33}33. Guyatt G, Oxman AD, Akl EA, Kunz R, Vist G, Brozek J, et al. GRADE guidelines: 1. Introduction - GRADE evidence profiles and summary of findings tables. J Clin Epidemiol 2011; 64:383-94.. The GRADE system provided a structured approach to assess the quality of evidence across studies for each outcome included in the review according to risk of bias, publication bias, inconsistency, indirectness, and imprecision ³²32. GRADE Working Group. Grading quality of evidence and strength of recommendations. BMJ 2004; 328:1490.^{), (33}33. Guyatt G, Oxman AD, Akl EA, Kunz R, Vist G, Brozek J, et al. GRADE guidelines: 1. Introduction - GRADE evidence profiles and summary of findings tables. J Clin Epidemiol 2011; 64:383-94.. This classification indicated low quality of evidence for consistent condom use and very low quality of evidence for reduction in unprotected sexual acts. We downgraded the quality of evidence twice for both outcomes, based on the wide confidence intervals, indicating imprecision, and because results from different intervention protocols, with differences in duration, providers, and delivery cannot be generalized to diverse populations of women living with HIV (indirectness). We also downgraded the quality of evidence for the reduction in unprotected sexual relations, considering the inconsistency criteria, since it was not possible to conduct subgroup analyses to explore the sources of the moderate heterogeneity. The summary of findings can be accessed in Table 1 of the Supplementary Material: https://www.dropbox.com/s/tjhjhozyn8h235o/Supplementary%20Material%20reviewed.pdf?dl=0.

We specifically considered that the imprecision could also relate to the lack of sample size calculation in 3 ³⁶36. Sikkema KJ, Wilson PA, Hansen NB, Kochman A, Neufeld S, Ghebremichael MS, et al. Effects of a coping intervention on transmission risk behavior among people living with HIV/AIDS and a history of childhood sexual abuse. J Acquir Immune Defic Syndr 2008; 47:506-13.^{), (39}39. Cornman DH, Kiene SM, Christie S, Fisher WA, Shuper PA, Pillay S, et al. Clinic-based intervention reduces unprotected sexual behavior among HIV-infected patients in KwaZulu-Natal, South Africa: results of a pilot study. J Acquir Immune Defic Syndr 2008; 48:553-60.^{), (41}41. Saleh-Onoya D, Reddy PS, Ruiter RA, Sifunda S, Wingood G, van den Borne B. Condom use promotion among isiXhosa speaking women living with HIV in the Western Cape Province, South Africa: a pilot study. AIDS Care 2009; 21:817-25. out of 8 included studies ³⁵35. Gilbert P, Ciccarone D, Gansky SA, Bangsberg DR, Clanon K, McPhee SJ, et al. Interactive "Video Doctor" counseling reduces drug and sexual risk behaviors among HIV-positive patients in diverse outpatient settings. PLoS One 2008; 3:e1988.^{), (38}38. Holstad MM, DiIorio C, Kelley ME, Resnicow K, Sharma S. Group motivational interviewing to promote adherence to antiretroviral medications and risk reduction behaviors in HIV infected women. AIDS Behav 2011; 15:885-96.^{), (40}40. Le Roux IM, Tomlinson M, Harwood JM, O'Connor MJ, Worthman CM, Mbewu N, et al. Outcomes of home visits for pregnant mothers and their infants: a cluster randomized controlled trial. AIDS 2013; 27:1461-71. and to the fact that the overall sample size across studies for both outcomes (in each follow-up assessment) appears too small to estimate a relevant public health impact from behavioral interventions on condom use. Based on the results of the meta-analysis, the optimal information size for the dichotomous outcome - consistent condom use - would require 4,356 participants in each intervention arm (e.g., P1 expected proportion in the control group 555/1,103= 0.50; P2 expected proportion in the intervention group 612/1,162 = 0.53; lowest p = 0.75; difference between P1 and P2 = 0.03; alpha and beta of 0.05 and 0.20, respectively ⁵¹51. Hulley SB, Cummings SR, Browner WS, Grady D, Hearst N, Newman TB. Designing clinical research. 2nd Ed. Philadelphia: Lippincott Williams & Wilkins; 2001.). Moreover, three of the studies included in the meta-analysis targeted both women and men, having lower percentages of female participants.

Assessment of publication bias

A meta-analysis can be vulnerable to publication bias if studies with less favorable results are not found. A useful test for publication bias is based on the funnel plot, which compares intervention effects estimated from individual studies against a measure of study size. In the absence of bias, the plot resembles a symmetrical inverted funnel ⁵²52. Sterne JA, Egger M, Smith GD. Systematic reviews in health care: Investigating and dealing with publication and other biases in meta-analysis. BMJ 2001; 323:101-5.. However, the test is underpowered to distinguish chance from real asymmetry when less than 10 studies are included in the meta-analysis ³¹31. Higgins JPT, Green SP. Cochrane handbook for systematic reviews of interventions. Version 5.0.0. Chichester: John Wiley; 2008., which was the case in this review. Even so, in order to explore evidence of publication bias, we performed funnel plots for both outcomes. For the dichotomous outcome, the funnel plot was quite symmetrical, while in the continuous outcome, which includes fewer studies, plot asymmetry could be observed (see Figures 1 and 2 in the Supplementary Material: https://www.dropbox.com/s/tjhjhozyn8h235o/Supplementary%20Material%20reviewed.pdf?dl=0). Considering the small number of studies included in both meta-analyses, we can hypothesize that asymmetry may be also related to true heterogeneity among studies with different sizes rather than indicating publication bias, since there were differences in the intensity of the interventions as well as among HIV+ women who lived in highly diverse contexts in terms of social and individual vulnerability.

Effects of interventions

In this updated review, we conducted meta-analyses for two different outcomes: consistent condom use and reduction in unprotected sexual intercourse, respectively. A meta-analysis of the 8 studies did not demonstrate an effect of behavioral interventions on consistent condom use among women living with HIV when compared to standard care or minimal HIV support interventions. No intervention effects on consistent condom use were noted at the 3-month follow-up (RR = 0.92; 95%CI: 0.73, 1.16; p = 0.48), 6-month follow-up (RR = 1.13; 95%CI: 0.96, 1.34; p = 0.15), and 12-month follow-up (RR = 0.91; 95%CI: 0.77, 1.08; p = 0.30) or the overall effect (RR = 1.02; 95%CI: 0.92, 1.12; p = 0.74).

The overall result for consistent condom use showed evidence of moderate heterogeneity, indicating some inconsistency across study results (τ² = 0.08; χ² = 19.92, df = 12, p = 0.07, I² = 40%). As shown in Figure 3, the higher heterogeneity for consistent condom use was found at the 6 month follow-up, probably related to positive results found by one study ³⁷37. DeMarco RF, Chan K. The Sistah Powah structured writing intervention: a feasibility study for aging, low-income, HIV-positive black women. Am J Health Promot 2013; 28:108-18.. Subgroup analyses could not distinguish statistically significant differences in the intervention effect considering interventions that exclusively targeted (versus did not exclusively target) women living with HIV, or between the countries where they were conducted, i.e., in North America compared to Africa (see Figures 3, 4 and 5 in the Supplementary Material: https://www.dropbox.com/s/tjhjhozyn8h235o/Supplementary%20Material%20reviewed.pdf?dl=0).

A combination of particular characteristics of DeMarco & Chan's study ³⁷37. DeMarco RF, Chan K. The Sistah Powah structured writing intervention: a feasibility study for aging, low-income, HIV-positive black women. Am J Health Promot 2013; 28:108-18. deserves to be mentioned, since it could be related to the positive results found in the meta-analysis. The Sistah Powah Structured Writing Intervention targeted aging, low-income, black women living with HIV, a group of women highly neglected by secondary prevention efforts because pregnancy is less likely and who face strong social vulnerability and stigma ⁵³53. Lopes F, Buchalla CM, Ayres JRCM. Mulheres negras e não-negras e vulnerabilidade ao HIV/AIDS no estado de São Paulo, Brasil. Rev Saúde Pública 2007; 41:39-46.. The intervention was conducted in small groups and was the only one that was exclusively peer-led, involved culturally relevant narrative techniques, and helped to build a social support network in a community setting. Considering the population and the intervention's characteristics jointly, its success in promoting consistent condom use could be linked to a more effective approach to empower women living with HIV, stimulating their autonomy and the adoption of adapted strategies to deal with HIV according to gender and in socially challenging settings.

As shown in Figure 4, the meta-analysis for reducing unprotected sexual intercourse (e.g., increased condom use - continuous outcome) showed no significant effects of the behavioral interventions when compared to standard care or minimal HIV support interventions at 6-month (MD = -1.80; 95%CI: -4.21, 0.62; p = 0.14) and 12-month follow-up (MD = -1.39; 95%CI: -2.29, 0.21; p = 0.09). However, significant heterogeneity was detected (τ² = 1.19, χ² = 9.37, df = 4, p = 0.05, I² = 57%), probably reflecting the diversity of studies included in the 6-month follow-up as well as the high imprecision observed in 1 study ³⁶36. Sikkema KJ, Wilson PA, Hansen NB, Kochman A, Neufeld S, Ghebremichael MS, et al. Effects of a coping intervention on transmission risk behavior among people living with HIV/AIDS and a history of childhood sexual abuse. J Acquir Immune Defic Syndr 2008; 47:506-13.. We were unable to further explore heterogeneity with subgroup analyses due to the small number of studies included for this outcome.

Considering the statistical analyses conducted individually by the authors of the studies included in the meta-analyses, all but 1 found positive results for increased condom use ⁴¹41. Saleh-Onoya D, Reddy PS, Ruiter RA, Sifunda S, Wingood G, van den Borne B. Condom use promotion among isiXhosa speaking women living with HIV in the Western Cape Province, South Africa: a pilot study. AIDS Care 2009; 21:817-25.. Eight studies considered a combined number of sexual events in which frequency rather than consistency of condom use was the primary outcome ²⁹29. Wingood GM, DiClemente RJ, Mikhail I, Lang DL, McCree DH, Davies SL, et al. A randomized controlled trial to reduce HIV transmission risk behaviors and sexually transmitted diseases among women living with HIV: the WiLLOW Program. J Acquir Immune Defic Syndr 2004; 37:S58-67.^{), (36}36. Sikkema KJ, Wilson PA, Hansen NB, Kochman A, Neufeld S, Ghebremichael MS, et al. Effects of a coping intervention on transmission risk behavior among people living with HIV/AIDS and a history of childhood sexual abuse. J Acquir Immune Defic Syndr 2008; 47:506-13.^{), (39}39. Cornman DH, Kiene SM, Christie S, Fisher WA, Shuper PA, Pillay S, et al. Clinic-based intervention reduces unprotected sexual behavior among HIV-infected patients in KwaZulu-Natal, South Africa: results of a pilot study. J Acquir Immune Defic Syndr 2008; 48:553-60.^{), (42}42. Echenique M, Illa L, Saint-Jean G, Avellaneda VB, Sanchez-Martinez M, Eisdorfer C. Impact of a secondary prevention intervention among HIV-positive older women. AIDS Care 2013; 25:443-6.^{), (43}43. Jones DL, Weiss SM, Malow R, Ishii M, Devieux J, Stanley H, et al. A brief sexual barrier intervention for women living with AIDS: acceptability, use, and ethnicity. J Urban Health 2001; 78:593-604.^{), (44}44. Teti M, Bowleg L, Cole R, Lloyd L, Rubinstein S, Spencer S, et al. A mixed methods evaluation of the effect of the Protect and Respect intervention on the condom use and disclosure practices of women living with HIV/AIDS. AIDS Behav 2010; 14:567-79.^{), (45}45. Kalichman SC, Rompa D, Cage M, DiFonzo K, Simpson D, Austin J, et al. Effectiveness of an intervention to reduce HIV transmission risks in HIV-positive people. Am J Prev Med 2001; 21:84-92.^{), (46}46. Fisher JD, Fisher WA, Cornman DH, Amico RK, Bryan A, Friedland GH. Clinician-delivered intervention during routine clinical care reduces unprotected sexual behavior among HIV-infected patients. J Acquir Immune Defic Syndr 2006; 41:44-52.. Another study originally used a composite safer sex score ³⁷37. DeMarco RF, Chan K. The Sistah Powah structured writing intervention: a feasibility study for aging, low-income, HIV-positive black women. Am J Health Promot 2013; 28:108-18.. Three other articles did not originally present data on intervention results by gender, even reporting that gender analyses were done and that no significant differences were found ³⁵35. Gilbert P, Ciccarone D, Gansky SA, Bangsberg DR, Clanon K, McPhee SJ, et al. Interactive "Video Doctor" counseling reduces drug and sexual risk behaviors among HIV-positive patients in diverse outpatient settings. PLoS One 2008; 3:e1988.^{), (36}36. Sikkema KJ, Wilson PA, Hansen NB, Kochman A, Neufeld S, Ghebremichael MS, et al. Effects of a coping intervention on transmission risk behavior among people living with HIV/AIDS and a history of childhood sexual abuse. J Acquir Immune Defic Syndr 2008; 47:506-13.^{), (39}39. Cornman DH, Kiene SM, Christie S, Fisher WA, Shuper PA, Pillay S, et al. Clinic-based intervention reduces unprotected sexual behavior among HIV-infected patients in KwaZulu-Natal, South Africa: results of a pilot study. J Acquir Immune Defic Syndr 2008; 48:553-60..

The current review also aimed to assess the effect of behavioral interventions on STI incidence, but only 2 studies ²⁹29. Wingood GM, DiClemente RJ, Mikhail I, Lang DL, McCree DH, Davies SL, et al. A randomized controlled trial to reduce HIV transmission risk behaviors and sexually transmitted diseases among women living with HIV: the WiLLOW Program. J Acquir Immune Defic Syndr 2004; 37:S58-67.^{), (41}41. Saleh-Onoya D, Reddy PS, Ruiter RA, Sifunda S, Wingood G, van den Borne B. Condom use promotion among isiXhosa speaking women living with HIV in the Western Cape Province, South Africa: a pilot study. AIDS Care 2009; 21:817-25. assessed this outcome. The studies had different timing of follow-up assessments and 1 one ²⁹29. Wingood GM, DiClemente RJ, Mikhail I, Lang DL, McCree DH, Davies SL, et al. A randomized controlled trial to reduce HIV transmission risk behaviors and sexually transmitted diseases among women living with HIV: the WiLLOW Program. J Acquir Immune Defic Syndr 2004; 37:S58-67. presented adequate data to be grouped by results related to STI. One study found significantly higher incidence of Chlamydia trachomatis (OR = 0.21; 95%CI: 0.07, 0.59; p < 0.05), Neisseria gonorrhoeae (OR = 0.10; 95%CI: 0.02, 0.49; p < 0.05), and Trichomona vaginalis (OR = 0.06; 95%CI: 0.01, 0.46; p < 0.05) in the control group than in the intervention at 3 months follow-up ⁴¹41. Saleh-Onoya D, Reddy PS, Ruiter RA, Sifunda S, Wingood G, van den Borne B. Condom use promotion among isiXhosa speaking women living with HIV in the Western Cape Province, South Africa: a pilot study. AIDS Care 2009; 21:817-25.. No significant difference was found for incidence of bacterial vaginosis. Wingood et al. ²⁹29. Wingood GM, DiClemente RJ, Mikhail I, Lang DL, McCree DH, Davies SL, et al. A randomized controlled trial to reduce HIV transmission risk behaviors and sexually transmitted diseases among women living with HIV: the WiLLOW Program. J Acquir Immune Defic Syndr 2004; 37:S58-67. reported that participants in the intervention group were not significantly less likely to have a Trichomonas infection any follow-up assessment but were significantly less likely to have an bacterial STI (Chlamydia or gonorrhea) at the 12-month follow-up (OR = 0.10; 95%CI: 0.01, 0.70; p = 0.023) and over the entire 12 months (OR = 0.20; 95%CI: 0.01, 0.06; p = 0.006). These findings indicate that behavioral interventions could be a promising strategy to reduce STI incidence even if it cannot be confirmed through meta-analysis.

Another 5 studies were included in this systematic review but did not provide sufficient data to combine their results, and we present them in a narrative review as follows. One non-randomized trial of an intervention delivered jointly for women and men living with HIV included 45% of female participants in the intervention group and 39% in the comparison ⁴⁶46. Fisher JD, Fisher WA, Cornman DH, Amico RK, Bryan A, Friedland GH. Clinician-delivered intervention during routine clinical care reduces unprotected sexual behavior among HIV-infected patients. J Acquir Immune Defic Syndr 2006; 41:44-52.. People living with HIV in the intervention group showed a significant reduction (b = 20.51; SE = 0.23, p < 0.05) in unprotected vaginal and anal intercourse and insertive oral sex over a follow-up of 18 months, while these behaviors increased among participants in the comparison arm (b = 0.51; SE = 0.19; p = 0.01). Interventions' effects remained significant when these analyses were performed separately by gender, and the effect was higher in men (p = 0.002) than in women (p = 0.04). In a more conservative measure (unprotected vaginal and anal sex only), authors found a trend toward a reduction in unprotected sex in the intervention group over time (b = 20.42; SE = 0.25; p = 0.09), and a significant increase among standard-of-care control participants (b = 0.61; SE = 0.21; p < 0.01). Similar results were found for both outcomes (broader and conservative) when considering only sexual acts with HIV-negative partners or those with unknown HIV status.

Another RCT ⁴⁵45. Kalichman SC, Rompa D, Cage M, DiFonzo K, Simpson D, Austin J, et al. Effectiveness of an intervention to reduce HIV transmission risks in HIV-positive people. Am J Prev Med 2001; 21:84-92. included 60 women living with HIV (32%) in the intervention arm and 38 (26%) in the comparison arm. Since the intervention content was tailored to gender, the latter was controlled throughout the analysis, although the results were not presented separately for women and men. The results did not suggest differences between intervention and control groups for number of sexual partners reported at 3 or 6 months follow-up or for rates of unprotected intercourse at the 3-month follow-up. However, there were significant differences between conditions for rates of unprotected sexual acts (OR = 2.2; 95%CI: 0.23, 4.17) and condom use rate at the 6-month follow-up (OR = -17.1; 95%CI: -27.94, -6.26) regardless of the partner's HIV status (OR and 95%CI calculated based on the reported means and standard deviations). Considering sexual practices only with HIV-negative partners, participants in the intervention group showed significantly lower mean rates of unprotected intercourse at 3 months (OR = 0.2; 95%CI: -0.22, 0.62) and 6 months (OR = 0.8; 95%CI: -0.34, 1.94), but no differences were found in the condom use rate (OR and 95%CI calculated based on the reported means and standard deviations). Potential moderators of the intervention effects were examined and no main interactions were found, including participant's gender.

Three other interventions were developed exclusively for women living with HIV and tested in the United States ⁴²42. Echenique M, Illa L, Saint-Jean G, Avellaneda VB, Sanchez-Martinez M, Eisdorfer C. Impact of a secondary prevention intervention among HIV-positive older women. AIDS Care 2013; 25:443-6.^{), (43}43. Jones DL, Weiss SM, Malow R, Ishii M, Devieux J, Stanley H, et al. A brief sexual barrier intervention for women living with AIDS: acceptability, use, and ethnicity. J Urban Health 2001; 78:593-604.^{), (44}44. Teti M, Bowleg L, Cole R, Lloyd L, Rubinstein S, Spencer S, et al. A mixed methods evaluation of the effect of the Protect and Respect intervention on the condom use and disclosure practices of women living with HIV/AIDS. AIDS Behav 2010; 14:567-79.. In a quasi-experimental study, Jones et al. ⁴³43. Jones DL, Weiss SM, Malow R, Ishii M, Devieux J, Stanley H, et al. A brief sexual barrier intervention for women living with AIDS: acceptability, use, and ethnicity. J Urban Health 2001; 78:593-604. reported that at the 3-month assessment, both groups increased male condom use reaching 40% of protected sexual events in the intervention group (p < 0.001) and 34% in the comparison arm (p < 0.01). Nine months post-intervention, no changes in male condom use were observed, but at both the 3- and 9-month assessments it was not clear if a inter-group analysis had been performed. Using a RCT design and applying only bivariate analysis, Echenique et al. ⁴²42. Echenique M, Illa L, Saint-Jean G, Avellaneda VB, Sanchez-Martinez M, Eisdorfer C. Impact of a secondary prevention intervention among HIV-positive older women. AIDS Care 2013; 25:443-6. found women living with HIV in the intervention group significantly (p < 0.05) reduced inconsistent condom use with all partners from baseline (20%) to 6-month follow-up (9.2%), while women in the control group did not. Finally, another RCT ⁴⁴44. Teti M, Bowleg L, Cole R, Lloyd L, Rubinstein S, Spencer S, et al. A mixed methods evaluation of the effect of the Protect and Respect intervention on the condom use and disclosure practices of women living with HIV/AIDS. AIDS Behav 2010; 14:567-79. reported that intervention participants were more likely to report condom use at 6 months (AOR = 17.13; 95%CI: 2.96, 99.10; p < 0.01) and 18 months (AOR = 270.04; 95%CI: 24.53, 2,971.94; p < 0.01).

Discussion

A previous systematic review and meta-analysis on behavioral interventions to promote condom use among women living with HIV was not able to demonstrate positive effects ³⁰30. Carvalho FT, Goncalves TR, Faria ER, Shoveller JA, Piccinini CA, Ramos MC, et al. Behavioral interventions to promote condom use among women living with HIV. Cochrane Database Syst Rev 2011; (9):CD007844.. Considering the need for a more accurate picture of these interventions and their implications for research and decision-making in public health, this study aimed to update and broaden the previous review, including newly published studies and adding a continuous outcome to the pooled analysis.

Concerning consistent condom use (dichotomous outcome), this updated version was unable to identify effects of behavioral interventions even after including other studies, maintaining the result of the original meta-analysis ³⁰30. Carvalho FT, Goncalves TR, Faria ER, Shoveller JA, Piccinini CA, Ramos MC, et al. Behavioral interventions to promote condom use among women living with HIV. Cochrane Database Syst Rev 2011; (9):CD007844.. As suggested previously ³⁰30. Carvalho FT, Goncalves TR, Faria ER, Shoveller JA, Piccinini CA, Ramos MC, et al. Behavioral interventions to promote condom use among women living with HIV. Cochrane Database Syst Rev 2011; (9):CD007844., we included a less rigorous outcome in the quantitative syntheses which was intended to identify a reduction in unprotected sexual acts and an increase in the frequency of condom use. Contrary to expectations, the inclusion of a continuous outcome in the updated review did not show positive intervention effects, thus corroborating a growing body of evidence showing low efficacy of behavioral interventios to prevent STI ⁵⁴54. Macaya Pascual A, Ferreres Riera JR, Campoy Sánchez A. Behavioral interventions for preventing sexually transmitted infections and unintended pregnancies: an overview of systematic reviews. Actas Dermo-Sifiliográficas (English Edition) 2016; 107:301-17.. Even adding some studies in this updated version, we found that data are still limited on the effects of behavioral inteventions on condom use among women living with HIV, and are based on small studies. Thus, our results might change when findings from larger studies are included.

Recent debates have questioned whether biomedical trial methods are the most fitting for assessing behavioral inteventions ¹⁸18. Joint United Nations Programme on HIV/AIDS. Social and behaviour change programming. Geneva: Joint United Nations Programme on HIV/AIDS; 2014.. Behavioral change is a complex and highly context-dependent phenomenon, in contrast to biomedical outcomes which are more objective and easier to measure and respond to - for example, morbidity assessed through blood tests or self-reported symptoms. According to Joint United Nations Programme on HIV/AIDS (UNAIDS) ¹⁸18. Joint United Nations Programme on HIV/AIDS. Social and behaviour change programming. Geneva: Joint United Nations Programme on HIV/AIDS; 2014., behavioral change interventions appear to be difficult to evaluate through RCTs and can be erroneously interpreted as ineffective. Still, behavioral change has been responsible for important early declines in HIV incidence in several countries with generalized epidemics ¹⁸18. Joint United Nations Programme on HIV/AIDS. Social and behaviour change programming. Geneva: Joint United Nations Programme on HIV/AIDS; 2014.. Promoting consistent condom use is still a central public health strategy to stop ongoing transmission and avoid negative effects of multiple sexually transmitted infections and/or superinfection in people living with HIV, especially in resource-limited settings where antiretroviral therapy is not widely accessible. The potentially false idea that behavioral interventions do not work could be overcome by carefully examining contextual aspects and designing studies with better methodological quality.

Contrary to findings in the meta-analysis, a different picture emerged when we examined the qualitative syntheses. Different statistical approaches conducted individually by each study showed positive results in all but one intervention ⁴¹41. Saleh-Onoya D, Reddy PS, Ruiter RA, Sifunda S, Wingood G, van den Borne B. Condom use promotion among isiXhosa speaking women living with HIV in the Western Cape Province, South Africa: a pilot study. AIDS Care 2009; 21:817-25., either considering consistent condom use and/or reducing the proportion of unprotected sexual acts. These discordant findings are probably related to the intention-to-treat approach assumed in the pooled analyses instead of the per-protocol analysis adopted by most of the studies.

Regarding reduction of STI incidence in women living with HIV, two studies individually mentioned favorable effects of behavioral interventions, but the results could not be pooled in a meta-analysis. STI diagnosis is a critical public health outcome in behavioral intervention trials, since solid evidence backs the biological pathways by which STI facilitate HIV transmission and the negative effects of multiple sexually transmitted infections, especially in women living with HIV ⁴4. Landes M, Thorne C, Barlow P, Fiore S, Malyuta R, Martinelli P, et al. Prevalence of sexually transmitted infections in HIV-1 infected pregnant women in Europe. Eur J Epidemiol 2007; 22:925-36.^{), (5}5. McClelland RS, Lavreys L, Katingima C, Overbaugh J, Chohan V, Mandaliya K, et al. Contribution of HIV-1 infection to acquisition of sexually transmitted disease: a 10-year prospective study. J Infect Dis 2005; 191:333-8.^{), (53}53. Lopes F, Buchalla CM, Ayres JRCM. Mulheres negras e não-negras e vulnerabilidade ao HIV/AIDS no estado de São Paulo, Brasil. Rev Saúde Pública 2007; 41:39-46.. We therefore emphasize that even small reductions in STI incidence could favor critical reductions in HIV morbidity and its associated treatment cost. Future behavioral interventions should include STI reduction among their main outcomes in order to better examine their effects.

Another key issue is that few RCTs were found with available data to evaluate the effects of interventions on condom use according to gender. Furthermore, behavioral interventions especially tailored for condom use promotion among women living with HIV are still scarce, which could explain why subgroup analyses could not find differences in intervention effects, based on whether they were exclusively tailored for women. Despite repeated research findings indicating the challenges faced by women living with HIV, more studies are needed to understand how gender-linked factors (e.g., skill-building to negotiate condom use, gender violence, and gender power imbalances regarding economic resources and employment) influence the effectiveness of behavioral interventions to promote condom use ¹⁶16. Santos NJ, Barbosa RM, Pinho AA, Villela WV, Aidar T, Filipe EMV. Contextos de vulnerabilidade para o HIV entre mulheres brasileiras. Cad Saúde Pública 2009; 25 Suppl 2:S321-33.^{), (54}54. Macaya Pascual A, Ferreres Riera JR, Campoy Sánchez A. Behavioral interventions for preventing sexually transmitted infections and unintended pregnancies: an overview of systematic reviews. Actas Dermo-Sifiliográficas (English Edition) 2016; 107:301-17.^{), (55}55. Chakrapani V, Newman PA, Shunmugam M, Dubrow R. Prevalence and contexts of inconsistent condom use among heterosexual men and women living with HIV in India: implications for prevention. AIDS Patient Care STDS 2010; 24:49-58.. A recent systematic review of behavioral interventions to improve contraceptive use for family planning among women living with HIV also found limited evidence to compare the interventions' results ⁵⁶56. Lopez LM, Hilgenberg D, Chen M, Denison J, Stuart G. Behavioral interventions for improving contraceptive use among women living with HIV. Cochrane Database Syst Rev 2013; (1):CD010243.. Among seven included studies, all in Africa, new use of condoms was more likely in women attending services delivering multi-level and integrated care compared to those in routine care in one study. The authors highlighted the lack of effectiveness of delivering standardized information compared to interventions focused on the specific needs and concerns of women living with HIV regarding family planning.

In addition, none of the included studies explicitly mentioned promotion of female condom use, implying that male condoms were the intervention target. This could be seen as an important limitation to such interventions, since male condoms are not a female-initiated contraceptive method. Therefore, interventions involving female condoms should be promoted. We also endorse and advocate interventions to promote pleasant and empowered settings for female and/or male condom use, especially among women living with HIV. Future studies should also try to better elucidate the diversity across women living with HIV, dealing with heterogeneous intervention effects, for example, among women planning to become pregnant, women with casual versus steady partners, women with seroconcordant or serodiscordant partners, and women with multiple partners. Such research would be useful for understanding how specific groups of women could take advantage of interventions to promote condom use as well as for identifying new strategies for designing interventions.

We recommend that behavioral interventions focusing on condom use promotion among women living with HIV could have greater public health impact if they were part of broad positive prevention programs delivered with a gender perspective (including women-initiated prevention options) and developing actions that involve male partners, family planning counseling, community empowerment, mental health and drug abuse treatment, and safe serostatus disclosure settings ¹¹11. Weeks MR, Zhan W, Li J, Hilario H, Abbott M, Medina Z. Female condom use and adoption among men and women in a general low-income urban U.S. population. AIDS Behav 2015; 19:1642-54.^{), (55}55. Chakrapani V, Newman PA, Shunmugam M, Dubrow R. Prevalence and contexts of inconsistent condom use among heterosexual men and women living with HIV in India: implications for prevention. AIDS Patient Care STDS 2010; 24:49-58.. As seen in the qualitative syntheses, few studies included issues beyond sexual risk behavior and none approached family planning or included women's partners. We agree that without addressing social and cultural norms that shape sexual behaviors, opportunities for individual-level behavioral change are limited ¹⁸18. Joint United Nations Programme on HIV/AIDS. Social and behaviour change programming. Geneva: Joint United Nations Programme on HIV/AIDS; 2014.. A new approach to assessment of interventions' effect on condom use in women living with HIV should thus include mediator and moderator factors that assess broad social norms and diversified cultural contexts where sexual practices take place as well as access to specialized and primary healthcare services.

The review process was minimally biased since searches were not restricted by language and included a comprehensive search of databases, conference proceedings, and trials registers as well as contact with experts. The same search strategy and inclusion criteria were applied in both versions. Still, the present systematic review has some limitations that need to be examined. The review's first version had a specific protocol ³⁰30. Carvalho FT, Goncalves TR, Faria ER, Shoveller JA, Piccinini CA, Ramos MC, et al. Behavioral interventions to promote condom use among women living with HIV. Cochrane Database Syst Rev 2011; (9):CD007844. while the present version did not, which could introduce bias. Even so, some of the analyses in the present version were included in the original protocol (e.g., subgroup analysis) as well as in the discussion of results in the first review (e.g., inclusion of a continuous outcome). In addition, some eligible studies ⁴²42. Echenique M, Illa L, Saint-Jean G, Avellaneda VB, Sanchez-Martinez M, Eisdorfer C. Impact of a secondary prevention intervention among HIV-positive older women. AIDS Care 2013; 25:443-6.^{), (43}43. Jones DL, Weiss SM, Malow R, Ishii M, Devieux J, Stanley H, et al. A brief sexual barrier intervention for women living with AIDS: acceptability, use, and ethnicity. J Urban Health 2001; 78:593-604.^{), (44}44. Teti M, Bowleg L, Cole R, Lloyd L, Rubinstein S, Spencer S, et al. A mixed methods evaluation of the effect of the Protect and Respect intervention on the condom use and disclosure practices of women living with HIV/AIDS. AIDS Behav 2010; 14:567-79.^{), (45}45. Kalichman SC, Rompa D, Cage M, DiFonzo K, Simpson D, Austin J, et al. Effectiveness of an intervention to reduce HIV transmission risks in HIV-positive people. Am J Prev Med 2001; 21:84-92. lacked data for inclusion in the meta-analyses, which may have affected the effect size estimates.

Most of the studies were based in clinics where participants were receiving regular HIV care and do not accurately reflect women living with HIV as a whole. No study included in the review had an adequate number of female participants, emphasizing the importance of further research with larger female sample sizes. Meta-analysis also assumes that interventions are sufficiently similar to be combined, while behavioral interventions entail some dissimilarity, which makes it more difficult to propose strict recommendations. Finally, condom use is a multi-causal outcome demanding multimodal and multilevel interventions ¹⁸18. Joint United Nations Programme on HIV/AIDS. Social and behaviour change programming. Geneva: Joint United Nations Programme on HIV/AIDS; 2014.. Evaluating behavior change interventions requires understanding how individuals perceive HIV risk and the ability to protect themselves, including knowledge of the available choices.

After assessing data on interventions in female participants following participation in behavioral interventions, we were unable to identify either increases in consistent condom use or reduction in unprotected sex among women living with HIV. In order to capture intervention effects on condom use among women, we strongly recommend multi-method evaluations involving HIV incidence modeling, meta-analyses, and surveys on behavioral and service utilization trends, as well as ethnographical and qualitative clinical trials.

Acknowledgments

The authors wish to thank the Brazilian National Research Council (CNPq), the Brazilian Ministry of Health, and the Rio Grande do Sul State Research Foundation (FAPERGS) for their financial support. Thanks also to Haschi Horvath and Andrew Anglemyer for the statistical advice and an anonymous reviewer for his/her careful review. FAPERGS - Call for Projects ARD/2013 and CNPq - Call for Projects n. 37/2008 MCT/MS.

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