ABSTRACT:

Introduction:

The HIV lipodystrophy syndrome is characterized by changes in metabolism, and body composition that increase cardiovascular risk of people living with HIV/AIDS (PLWHA) using highly active antiretroviral therapy (HAART).

Objective:

To assess the prevalence of lipodystrophy and changes in lipid and glucose metabolism in PLWHA in use of HAART.

Methods:

For the anthropometric evaluation we measured weight, height and abdominal circumference (AC). For the lipodystrophy evaluation we conducted physical examination (subjective) and the (objective) examination of absorptiometry with X-ray dual energy (DEXA) by fat mass ratio (FMR). We also conducted lipid profile tests and fasting glucose and used the criteria suggested by The National Cholesterol Education Program III for metabolic disorders classification.

Results:

The final sample consisted of 262 patients with a mean age of 44.3 ± 10.2 years. Lipodystrophy, according to the physical examination, was present in 47.7% (95%CI 41.7 - 53.8) of patients, while the prevalence using FMR (DEXA) was 40.8% (95%CI 33.1 - 48.5). Most (53.0%; 95%CI 47.0 - 59.1) of the patients showed increased abdominal adiposity according to AC. The most prevalent metabolic alterations were reduced HDL (67.6%; 95%CI 61.9 - 73.2) and hypertriglyceridemia (55.7%; 95%CI 49.7 - 61.7).

Conclusion:

The high prevalence of lipodystrophy and changes in lipid and glucose metabolism show the importance of early intervention in this group of patients to prevent cardiovascular complications.

Keywords:
Prevalence; Lipodystrophy; Metabolic diseases; Body fat; HIV; Dyslipidemia

INTRODUCTION

The number of people living with HIV/AIDS (PLWHA) increases each year, all over the world. Worldwide estimates indicate that by the end of 2014, approximately 36.9 million people lived with HIV¹1. World Health Organization (WHO). HIV/AIDS: fact sheet no. 360. Geneva: WHO; 2015. [Internet]. Disponível em: Disponível em: http://www.who.int/mediacentre/factsheets/fs360/en/ (Acessado em 17 de fevereiro de 2016).
http://www.who.int/mediacentre/factsheet... .

In Brazil, since the identification of the first case, in 1980, until June 2015, 798,366 PLWHA were registered, and over 290 thousand deaths were identified with AIDS as the primary cause²2. Brasil. Ministério da Saúde. Boletim Epidemiológico AIDS-DST. 2015: ano IV, nº 01. [Internet]. Disponível em: Disponível em: http://www.aids.gov.br/sites/default/files/anexos/publicacao/2015/58534/boletim_aids_11_2015_web_pdf_19105.pdf (Acessado em 17 de fevereiro de 2016).
http://www.aids.gov.br/sites/default/fil... .

In the 1990s, with the advent of combined highly active antiretroviral therapy (HAART), it was possible to reduce the mortality and morbidity of AIDS and allows for a better quality of life for those with HIV³3. Campos LN, Cesar CC, Guimarães MD. Quality of life among HIV-infected patients in Brazil after initiation of treatment. Clinics 2009; 64(9): 867-75. DOI: 10.1590/S1807-59322009000900007
https://doi.org/10.1590/S1807-5932200900... . Despite their benefits and efficacy, the interaction between HAART with the infection itself and inflammation caused by HIV is associated with severe adverse effects, such as metabolic alterations and abnormal redistribution of body fat. These changes are called HIV lipodystrophy syndrome (HIVLS)⁴4. Loonam CR, Mullen A. Nutrition and the HIV-associated lipodystrophy syndrome. Nutr Res Rev 2012; 25(2): 267-87. DOI: 10.1017/S0954422411000138
https://doi.org/10.1017/S095442241100013... .

The abnormal redistribution of body fat (lipodystrophy) in PLWHA using HAART is characterized by loss of subcutaneous fat, mainly on the face, gluteal region and limbs (lipoatrophy), as well as by accumulation of fat on the back of the cervix, breasts and visceral region (lipohypertrophy). Lipodystrophy is the focal point of HIVLS and may occur alone or associated with insulin resistance, type II diabetes, dyslipidemia, hypertension, endothelial dysfunction and altered production of cytokines and adipokines⁵5. Giralt M, Domingo P, Villarroya F. Adipose tissue biology and HIV-infection. Best Pract Res Clin Endocrinol Metab 2011; 25(3): 487-99. DOI: 10.1016/j.beem.2010.12.001
https://doi.org/10.1016/j.beem.2010.12.0... . These alterations are similar to the ones occurred in the metabolic syndrome and characterize an atherogenic metabolic profile, increasing the risk for cardiovascular diseases in these patients⁶6. Marcason W. What does the term “HIV-associated lipodystrophy” mean? J Am Diet Assoc 2009; 109(2): 364. DOI: 10.1016/J.JADA.2008.12.005
https://doi.org/10.1016/J.JADA.2008.12.0... .

The diagnosis of lipodystrophy may be done through method such as clinal exams, self-report, electrical bio impedance (BIA) or techniques that provide quantitative data about adipose tissue such as dual energy X-ray absorptiometry (DEXA), magnetic resonance imaging (MRI) and computed tomography (CT)⁷7. Finkelstein JL, Gala P, Rochford R, Glesby MJ, Mehta S. HIV/AIDS and lipodystrophy: implications for clinical management in resource-limited settings. J Int AIDS Soc 2015; 15(18): 19033. DOI: 10.7448/IAS.18.1.19033
https://doi.org/10.7448/IAS.18.1.19033... . The imaging methods have high operational cost, limited availability and, in the case of DEXA and CT, involve ionizing exposure, making it rather difficult to be used in clinical practice. Thus, the evaluation by subjective method, which includes the patient’s reports on the alterations in the distribution of body fat, associated to the confirmation of those alterations by the inspection of the evaluator has been the currently most used one⁸8. Currier J, Carpenter C, Daar E, Kotler D, Wanke C. Identifying and managing morphologic complications of HIV and HAART. AIDS Read 2012; 12(3): 114-9, 124-5..

DEXA is a reference technique in the evaluation of body composition⁹9. Haarbo J, Gotfredsen A, Hassager C, Christiansen C. Validation of body composition by dual energy X-ray absorptiometry (DEXA). Clin Physiol 1991; 11(4): 331-41.. In a French study from 2005, Bonnet et al. proposed, for the first time, an objective index obtained by DEXA to identify lipodystrophy, the fat mass ratio (FMR), which seems to allow for ta accurate and early diagnosis¹⁰10. Bonnet E, Delpierre C, Sommet A, Mario-Latard F, Hervé R, Aquilina C, et al. Total body composition by DXA of 241 HIV-negative men and 162 HIV-infected men: proposal of reference values for defining lipodystrophy. J Clin Densitom 2005; 8(3): 287-92.. FMR is defined as a percentage of torso fat divided by the percentage of fat in the lower limbs. More recently, Beraldo et al. proposed a cutoff point of 1.26 to identify lipodystrophy in the Brazilian population¹¹11. Beraldo RA, Vassimon HS, Aragon DC, Navarro AM, Paula FJ, Foss-Freitas MC. Proposed ratios and cutoffs for the assessment of lipodystrophy in HIV-seropositive individuals. Eur J Clin Nutr 2015; 69(2): 274-8. DOI: 10.1038/ejcn.2014.149
https://doi.org/10.1038/ejcn.2014.149... .

There is still no consensus as for what is the best way to diagnose this disorder. Thus, due to the different methods and criteria used in these studies, the prevalence has been ranging between 1 and 84%¹²12. Dube NM, Summers R, Tint KS, Mayayise G. A pharmacovigilance study of adults on highly active antiretroviral therapy. South Africa: 2007 - 2011. Pan Afr Med J 2012; 11: 39.. A research carried out in Brazil, by Diehl et al., evaluated 180 HIV carriers older than 18 years of age through subjective method and found a prevalence of 55% of HIVLS. However, the authors observed, through clinical data, that 73% of those assessed had some kind of body fat, though only 76% of these individuals reported such alteration¹³13. Diehl LA, Dias JR, Paes AC, Thomazini MC, Garcia LR, Cinagawa E, et al. Prevalência da lipodistrofia associada ao HIV em pacientes ambulatoriais brasileiros: relação com síndrome metabólica e fatores de risco cardiovascular. Arq Bras Endrocrinol Metab 2008; 52(4): 658-67. DOI: 10.1590/S0004-27302008000400012
https://doi.org/10.1590/S0004-2730200800... .

Due to the fact that alterations in body fat distribution and lipid and glucose metabolism significantly increase morbidity and mortality of PLWHA in HAART, it is essential to early identify the risk for cardiovascular diseases development. Thus, the objective of the present study was to evaluate the prevalence of lipodystrophy and lipid and glucose metabolism alterations in PLWHA using HAART.

METHODS

It is a cross-sectional study carried out in the University Hospital of the School of Medicine of Ribeirão Preto (Hospital Universitário da Faculdade de Medicina de Ribeirão Preto - HC/FMRP). The PLWHA were selected in outpatient units belonging to the Specialized Unit for Infectious Diseases Treatment (Unidade Especializada para Tratamento de Doenças Infectocontagiosas - UETDI). The UETDI is a specialized reference unit which assists people living with HIV/AIDS across the country, which, currently, serves approximately 1,800 people.

The study was approved by the Research Ethics Committee of the institution (HCRP protocol No. 17484/2013). The patients in outpatient units who met the selection criteria were invited to participate in the research Project and all volunteers who accepted it singed the Informed Consent.

Inclusion criteria were: HIV positive patients, being on HAART and having stable weight (oscillations below 10% during the previous year).

Exclusion criteria were: edema, thyroid diseases, chronic renal failure, lung disease, liver alterations, signs and symptoms of opportunistic infections and presence of a pacemaker or metal prosthesis.

Information were obtained about the use of lipid-lowering and hypoglycemic agents, currently used antiretrovirals and biochemical tests (viral load and CD4 T cells).

All anthropometric measures were performed in the meeting by trained personnel. Before starting the evaluation, patients should remove all metal accessories and wear light clothing. They were questioned about bladder emptying, practice of physical activity within the last 12 hours and consumption of alcohol within 24 hours prior to the evaluation.

CLINICAL TESTING FOR LIPODYSTROPHY CLASSIFICATION

For the classification of lipodystrophy, individuals should report peripheral lipoatrophy confirmed by clinical examination, accompanied or not by lipohypertrophy⁹9. Haarbo J, Gotfredsen A, Hassager C, Christiansen C. Validation of body composition by dual energy X-ray absorptiometry (DEXA). Clin Physiol 1991; 11(4): 331-41..

All assessments were carried out by the same investigators.

DEXA FOR LIPODYSTROPHY CLASSIFICATION

DEXA testing was carried out using a model of Hologic instrument (Discovery Wi, QDR^® series, Waltham, MA, USA) operated by a trained technician, strictly following standard procedures.

The FMR was calculated as the percentage of fat in the torso divided by the one of lower limbs, obtained by DEXA. The cutoff point for lipodystrophy classification was 1.26¹¹11. Beraldo RA, Vassimon HS, Aragon DC, Navarro AM, Paula FJ, Foss-Freitas MC. Proposed ratios and cutoffs for the assessment of lipodystrophy in HIV-seropositive individuals. Eur J Clin Nutr 2015; 69(2): 274-8. DOI: 10.1038/ejcn.2014.149
https://doi.org/10.1038/ejcn.2014.149... .

ANTHROPOMETRY FOR THE ASSESSMENT OF BODY FAT DISTRIBUTION

The body weight, in kilograms, was measured with an electronic Filizola platform scale, with a maximum capacity of 300 kg and precision of 0.1 kg. The height was measured with a stadiometer with an accuracy of 0.1 cm.

The body mass index (BMI) was calculated as weight (kg) divided by height (m) squared.

Circumference measures were taken using a metal measuring tape, Sanny with accuracy of 0.1 cm and maximum length of 2 m. The assessment of abdominal circumference (AC) was performed at the midpoint between the last rib and the iliac crest in a horizontal plane. The hip circumference (HC) was taken in the region of the largest circumference between abdomen and thigh¹⁴14. Lohman TG, Roche AF, Martorell R. Anthropometric standardization reference manual. Champaign: Human Kinetics Books; 1988.. The waist-hip ration (WHR) was calculated by the division of AC (cm) by HC (cm). The reference values for metabolic alterations risk by the World Health Organization (WHO) were considered¹⁵15. World Health Organization (WHO). Physical status: the use of and interpretation of anthropometry, report of a WHO expert committee. Geneva: WHO; 1995; 854: 378. [Internet]. Disponível em: Disponível em: http://whqlibdoc.who.int/trs/WHO_TRS_854.pdf (Acessado em 22 de fevereiro de 2016).
http://whqlibdoc.who.int/trs/WHO_TRS_854... .

BIOCHEMICAL ANALYSIS

Serum lipid concentrations (total cholesterol = TC, triglycerides = TG and high-density lipoprotein = HDL) were measured by enzymatic colorimetric method using the COBAS INTEGRA 400 instrument (Roche Diagnostics, Indianapolis, IN, EUA). The low-density lipoprotein (LDL) was calculated the Friedewald’s formula [LDL = TC - (TGs / 5 + HDL)]. Plasmatic glucose was determined in an automatic analyzer (2300 STAT, Yellow Springs Instruments Inc., Yellow Springs, OH, EUA).

Alterations were considered: TC ≥ 220 mg/dL, TG ≥ 150 mg/dL, HDL ≤ 40 mg/dL, LDL ≥ 130 mg/dL or in dyslipidemia treatment; fasting blood glucose ≥ 100 mg/dL or in treatment¹⁶16. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of the third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults. JAMA 2001; 285(19): 2486-97..

SAMPLE CALCULATION AND STATISTICAL ANALYSIS

A sample calculation was performed for the study. Considering a sample of 50% lipodystrophy, a population of 800 follow-up patients in the unit (within the age range of the study) and a tolerable absolute error of 5%. The sample size necessary for a real lipodystrophy prevalence estimate would be 260 individuals.

All continuous variables were presented in means and standard deviations and the categorical variables in frequencies and percentages accompanied by their confidence intervals of 95% (95%CI). The comparison between groups used the unpaired Student’s t-test and χ² test, considering a normal distribution (Kolmogorov-Smirnov test). A significance level of 5% was considered. The analyses used the Bioestat 5.3 software.

RESULTS

In the period from January 2011 to December 2013, 262 PLWHA were assessed (56.8% males) with mean age of 44.3 ± 10.1 years. The mean values found for CD4+ T were under control, and the majority of patients was undetectable viral load (< 50 copies/mL). The female subgroup had a significantly longer time of HAART use than the male one (Table 1).

As for the HAART regimen, 54.5% of patients used the combination of two nucleoside reverse-transcriptase inhibitors (NRTI) in addition to a non-nucleoside reverse-transcriptase inhibitor (NNRTI); 37.7% used the combination of two NRTI in addition to a protease inhibitor (PI); 6.1% used a combination of NRTI in addition to a NNRTI and a PI; and 1.5% used the combination with integrase inhibitor (II).

Regarding anthropometric variables, 51.9% of individuals were overweight, according to their BMI, and 53% had AC alteration (Table 2). The female subgroup had higher BMI values and fat mass, however, WHR, FMR and lean mass values were significantly lower in relation to the male subgroup (Table 3). Higher prevalence of alterations in BMI, AC and WHR was found in the female subgroup.

Biochemical analysis indicated that most individuals evaluated had alterations in their triglyceride and HDL concentrations, and the male subgroup had higher prevalence of hypertriglyceridemia, while the female subgroup had higher prevalence of low HDL-C concentrations. As for glucose metabolism, approximately 25% of those evaluated had elevated plasma glucose (Table 2).

Data show that 47.7% of those assessed had lipodystrophy according to the subjective evaluation method, with no significant difference between genders. On the other hand, the male subgroup had higher prevalence of lipodystrophy by FMR score. It is important to note that, due to the elevated costs of the procedure, only 157 (60.7%) of the individuals were submitted to DEXA evaluation, 75.8% were males. Among all the ones evaluated by DEXA, 40.8% were diagnosed with lipodystrophy according to the FMR score.

There were no differences in the prevalences of lipodystrophy between patients using PIs and the ones who were not, both by subjective and objective evaluations (p = 0.68 e p = 0.46; respectively).

Of the patients evaluated, 29.3% were smokers and 6.1% were formed smokers. Only eight (3.0%) were considered active, i.e., practiced physical activities for at least 150 minutes a week.

DISCUSSION

The present study presents as main results the high prevalence of metabolic alterations and the resdistribution of body fat if PLWHA in HAART.

The studied group consists of a population with long periods of positive HIV. The atherogenic lipid profile of the majority of patients assessed is in agreement with the standard risk for metabolic and cardiovascular diseases due to redistribution of body fat, in which there is central accumulation and peripheral loss. The data found are worrisome due to the elevated incidence of acute myocardial infarction and stroke in this population¹⁷17. Law MG, Friis-Moller N, El-Sadr WM, Weber R, Reiss P, D’Arminio Monforte A, et al. The use of the framingham equation to predict myocardial infarctions in HIV-infected patients: comparison with observed events in the D:A:D study. HIV Med 2006; 7(4): 218-30. DOI: 10.1111/j.1468-1293.2006.00362.x
https://doi.org/10.1111/j.1468-1293.2006... .

The adipose tissue remains as a major trigger of metabolic alterations and the development of chronic diseases and its redistribution is the focal point of lipodystrophy syndrome.

It is well known the abdominal adipose tissue synthesizes and secretes several mediators and cytokines which participate in the mechanisms leading to dyslipidemia, insulin resistance, hypertension and atherosclerosis¹⁸18. Giorgio F, Laviola L, Eriksson JW. Regional differences of insulin action in adipose tissue: insights from in vivo and in vitro studies. Acta Physiol Scand 2005; 183(1): 13-30. DOI: 10.1111/j.1365-201X.2004.01385.x
https://doi.org/10.1111/j.1365-201X.2004... ^,1919. Harmelen VV, Reynisdottir S, Eriksson P, Thörne A, Hoffstedt J, Lönnqvist F, et al. Leptin secretion from subcutaneous and visceral adipose tissue in women. Diabetes 1998; 47(6): 913-7.. Also known as adipocyte, according to their location, it presents different metabolic characteristics, visceral adiposity being the one high the greatest impact on the deterioration of insulin sensitivity. However, it seems that not only visceral fat has an unfavorable metabolic behavior, but also the abdominal subcutaneous fat, especially the one below the abdominal fascia²⁰20. Kelley DE, Thaete FL, Troost F, Huwe T, Goodpaster BH. Subdivisions of subcutaneous abdominal adipose tissue and insulin resistance. Am J Physiol Endocrinol Metab 2000; 278(5): E941-8.. On the other hand, the gluteo-femoral subcutaneous adipose tissue seems to have a protective role regarding insulin resistance²¹21. Weber RV, Buckley MC, Fried SK, Kral JG. Subcutaneous lipectomy causes a metabolic syndrome in hamsters. Am J Physiol Regul Integr Comp Physiol 2000; 279(3): R936-43. Thus, in case of body fat redistribution, the two factors (lipoatrophy and lipohypertrophy) tend to contribute to a worsening of the metabolic profile.

The present study found more altered mean values of TC, TG, LDL and glycemia when compared to the ones of a national study carried out in Rio de Janeiro, which assessed 203 seropositive patients²²22. Leite LH, Sampaio AB. Metabolic abnormalities and overweight in HIV/AIDS persons-treated with antiretroviral therapy. Rev Nutr 2008; 21(3): 277-83. DOI: 10.1590/S1415-52732008000300002
https://doi.org/10.1590/S1415-5273200800... .

When comparing the presence of metabolic adverse effects in the studied patients, it is observed that the prevalences of hypercholesterolemia, hypertriglyceridemia, elevated LDL and altered fasting glycemia are slightly higher than the prevalences found in the study by Domingos and colleagues, whose objective was to evaluate the presence of metabolic abnormalities in 292 PLWHA in HAART²³23. Domingos H, Cunha RV, Paniago AM, Martins DM, Elkhoury EB, Souza AS. Metabolic effects associated to the highly active antiretroviral therapy (HAART) in AIDS patients. Braz J Infect Dis 2009; 13(2): 130-6. DOI: 10.1590/S1413-86702009000200012
https://doi.org/10.1590/S1413-8670200900... . There was a greater prevalence of reduced HDL, considering our study had a higher one (67.6 versus 42.8%). These data confirm the high prevalence of lipid and glucose metabolism associated with HIV/HAART.

PIs have been more often associated to the development of the lipodystrophy syndrome, although there was no difference in the prevalence of lipodystrophy between the groups using or not PI in the present study. It can be justified by the fact that all patients use NRTI, which is a drug class that has been named in studies as the main cause for lipodystrophy through the induction of adipocyte apoptosis due to mitochondrial toxicity²⁴24. Bedimo RJ. Body-fat abnormalities in patients with HIV: progress and challenges. J Int Assoc Physicians AIDS Care (Chic) 2008; 7(6): 292-305. DOI: 10.1177/1545109708328931
https://doi.org/10.1177/1545109708328931... .

Some recent researches conclude the use of HAART is not the only determinant of these changes in the nutritional profile (despite their direct association with adipose tissue and insulin resistance), but rather their sum with genetic, environmental and nutritional factors²⁵25. Mariz CA, Albuquerque MF, Ximenes RA, Melo HR, Bandeira F, Oliveira TG, et al. Body mass index in individuals with HIV infection and factors associated with thinness and overweight/obesity. Cad Saúde Pública 2011; 27(10): 1997-2008. DOI: 10.1590/S0102-311X2011001000013
https://doi.org/10.1590/S0102-311X201100... .

The prevalence of clinical dystrophy in this study was similar to the one found in another national study of similar size²³23. Domingos H, Cunha RV, Paniago AM, Martins DM, Elkhoury EB, Souza AS. Metabolic effects associated to the highly active antiretroviral therapy (HAART) in AIDS patients. Braz J Infect Dis 2009; 13(2): 130-6. DOI: 10.1590/S1413-86702009000200012
https://doi.org/10.1590/S1413-8670200900... . In an article by Soares et al.²⁶26. Soares LR, Silva DC, Gonsalez CR, Batista FG, Fonseca LA, Duarte AJ, et al. Discordance between body mass index and anthropometric measurements among HIV-1-infected patients on antiretroviral therapy and with lipoatrophy/lipohypertrophy syndrome. Rev Inst Med trop S Paulo 2015; 57(2): 105-10. DOI: 10.1590/S0036-46652015000200002
https://doi.org/10.1590/S0036-4665201500... with 227 PLWHA, the prevalence of lipodystrophy found through subjective method was 40%, the highest prevalence was observed among women (44 versus 38.8%), as observed in our study (56.5 versus 48.6%). On the other hand, Diehl et al.¹³13. Diehl LA, Dias JR, Paes AC, Thomazini MC, Garcia LR, Cinagawa E, et al. Prevalência da lipodistrofia associada ao HIV em pacientes ambulatoriais brasileiros: relação com síndrome metabólica e fatores de risco cardiovascular. Arq Bras Endrocrinol Metab 2008; 52(4): 658-67. DOI: 10.1590/S0004-27302008000400012
https://doi.org/10.1590/S0004-2730200800... found a higher prevalence of lipodystrophy among men (68 versus 46%), as observed here by the FMR index.

The accuracy of clinical definition for lipodystrophy depends on the skills of the observer, which means specialist ones grant greater precision. Thus, this method is rather difficult be used by less experienced professionals in the area²⁷27. Freitas P, Santos AC, Carvalho D, Pereira J, Marques R, Martinez E, et al. Fat mass ratio: an objective tool to define lipodystrophy in HIV-infected patients under antiretroviral therapy. J Clin Densitom 2010; 13(2): 197-203. DOI: 10.1016/j.jocd.2010.01.005
https://doi.org/10.1016/j.jocd.2010.01.0... . In addition, many patients may not report changes in their body composition, which may make diagnosis difficult and, thus, contribute to the differences found in prevalences between studies.

No other national study evaluated the prevalence of lipodystrophy using FMR (DEXA) as an instrument. DEXA presents great accuracy of results, however, their cos tis high, thus it is not widely available. In addition to the subjective method used in clinical practice, the objective method suggested by Carr et al.²⁸28. Carr A, Emery S, Law M, Puls R, Lundgren JD, Powderly W. HIV lipodystrophy case definition study group. An objective case definition of lipodystrophy in HIV-infected adults: a case-control study. Lancet 2003; 361(9359): 726-35. uses many criteria which make this model complex and of limited use for the clinical practice.

In the male subgroup, lipodystrophy prevalences evaluated by both method (subjective and DEXA) were more concordant than the ones in the female subgroup, possibly due to the fact the cutoff point for FMR evaluation was previously standardized in men¹¹11. Beraldo RA, Vassimon HS, Aragon DC, Navarro AM, Paula FJ, Foss-Freitas MC. Proposed ratios and cutoffs for the assessment of lipodystrophy in HIV-seropositive individuals. Eur J Clin Nutr 2015; 69(2): 274-8. DOI: 10.1038/ejcn.2014.149
https://doi.org/10.1038/ejcn.2014.149... . These results suggest future studies propose cutoff point in order to identify lipodystrophy by using FMR in females, once that DEXA method is more accurate to contribute in the assessment of prevalence of lipodystrophy in scientific studies.

The high prevalence of increased AC (specially in females, 77.2%) justified the atherogenic profile of these patients, considering a recent analysis found that this anthropometric measure is a good tool to indicate metabolic alterations in the seropositive population. The AC assesses the deposition of central fat in the abdominal region and abdominal obesity is a greater risk cardiovascular factor than overall obesity²⁹29. Beraldo RA, Meliscki GC, Silva BR, Navarro AM, Bollela VR, Schmidt A, et al. Comparing the ability of anthropometric indicators in identifying metabolic syndrome in HIV patients. PLoS One 2016; 11(2): e0149905. DOI: 10.1371/journal.pone.0149905
https://doi.org/10.1371/journal.pone.014... .

A study by Freitas and colleagues, the prevalence of abdominal lipodystrophy among women also reached the 80% range, double the prevalence of males, corroborating the present study²⁷27. Freitas P, Santos AC, Carvalho D, Pereira J, Marques R, Martinez E, et al. Fat mass ratio: an objective tool to define lipodystrophy in HIV-infected patients under antiretroviral therapy. J Clin Densitom 2010; 13(2): 197-203. DOI: 10.1016/j.jocd.2010.01.005
https://doi.org/10.1016/j.jocd.2010.01.0... .

In addition to HAART adverse effects (fat redistribution and metabolic alterations) and the chronic inflammation by the virus, traditional risk factors due to inadequate habits also contributed to the increase of coronary disease³⁰30. d’Ettorre G, Ceccarelli G, Pavone P, Girolamo G, Schietroma I, et al. What happens to cardiovascular system behind the undetectable level of HIV viremia? AIDS Res Ther 2016; 13: 21. DOI: 10.1186/S12981-016-0105-z
https://doi.org/10.1186/S12981-016-0105-... . In this context, patients analyzed here were found under these inadequate habits, considering a considerable portion consists of smokers and sedentary people.

HAART has been initiated earlier and earlier, once despite their adverse effects, their benefits outweigh the clinical impact of lipodystrophy, reducing diseases related to AIDS and mortality³¹31. Sanchez G, Gonzalez-Cordon A, Rojas J, Blanco J, Blanch J, Lonca M, et al. Long-term impact of lipodystrophy on the risk of morbidity and mortality: a 20-year longitudinal cohort study. J Int AIDS Soc 2016; 19(8): 21487.. The choice of ideal ART drugs combo should be individualized and have the primary objective of reducing viral load and improving immunological response, however, it should be the least likely possible to cause metabolic abnormalities. Thus, the evaluation of cardiovascular risk should be continuous in all HAART patients³²32. Hemkens LG, Bucher HC. HIV infection and cardiovascular disease. Eur Heart J 2014; 35(21): 1373-81. DOI: 10.1093/eurheartj/eht528
https://doi.org/10.1093/eurheartj/eht528... .

The present study had some limitations, in particular by being cross-sectional, which does not allow for long term outcome observation. However, clinical data obtained by specialized professionals and the use of an accurate method for the quantitative evaluation of fat and lean mass ensure high confidence to the results.

CONCLUSION

Finally, the atherogenic metabolic profile of a large part of evaluated patients indicates the importance of early interventions. Thus, the encouragement of lifestyle changes with nutritional follow-up and orientation to regular physical exercise practice and, as a last resource, a change in the therapeutic regimen (considering the responses for each regimen are individual) may contribute to improve the metabolic profile and consequently reduce the cardiovascular risk of these patients.

ACKNOWLEDGEMENTS

The authors would like to thank the Special Unit for Infectious Diseases Treatment (Unidade Especial de Tratamento em Doenças Infecciosas).

References

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