|Year : 2014 | Volume
| Issue : 2 | Page : 94-98
Metabolic abnormalities and body composition in Human Immunodeficiency Virus-infected patients receiving highly active anti-retroviral therapy
Irshad Ali1, Reetu Devi Keisam2, Avinash Keisam3, Lallan Prasad1, Ranabir Salam1, Premchand Singh Thangjam1
1 Department of Medicine, Regional Institute of Medical Sciences, Imphal, Manipur, India
2 Department of Physiology, Jawaharlal Nehru Institute of Medical Sciences, Imphal, Manipur, India
3 Department of Community Medicine, Imphal, Manipur, India
|Date of Web Publication||6-May-2014|
Singjamei, Chingamakha, NingthoujamLeikai, Liwa Road, Imphal, Manipur - 7950 08
Source of Support: None, Conflict of Interest: None
Background: With the advent of highly active antiretroviral therapy (HAART) metabolic abnormalities such as dyslipidaemia, changes in fat distribution and insulin resistance have been observed with increasing frequency in patients with Human Immunodeficiency Virus (HIV) infection.
Aims: This study was undertaken to (i) assess body composition and the metabolic effects of HAART in HIV infected patients and (ii) compare the above variables between different 1 st and 2 nd ART regimens of National AIDS Control Organization of India.
Methods and Material: 201 HIV patients receiving HAART for more than 3 months were studied. Body mass composition was measured using TANITA segmental body composition monitor. The metabolic parameters measured included blood glucose, serum cholesterol and serum triglycerides.
Results: Lipodystrophy was observed in 21.40% patients. The mean body mass index (BMI) was 18.24 ± 3.18 and mean visceral fat mass was 4.16 kg. Altered lipid profile was observed in 26.86% patients (25.55% on 1 st line and 38.09% on 2 nd line) and impaired glucose tolerance was seen in 7.96% (6.66% on 1 st line and 19.04% on 2 nd line).
Conclusions: HAART has significant effect on the body mass composition and metabolic parameters.
Keywords: Highly active anti-retroviral therapy, introduction, lipodystrophy, metabolic abnormalities
|How to cite this article:|
Ali I, Keisam RD, Keisam A, Prasad L, Salam R, Thangjam PS. Metabolic abnormalities and body composition in Human Immunodeficiency Virus-infected patients receiving highly active anti-retroviral therapy. J Med Nutr Nutraceut 2014;3:94-8
|How to cite this URL:|
Ali I, Keisam RD, Keisam A, Prasad L, Salam R, Thangjam PS. Metabolic abnormalities and body composition in Human Immunodeficiency Virus-infected patients receiving highly active anti-retroviral therapy. J Med Nutr Nutraceut [serial online] 2014 [cited 2023 Mar 24];3:94-8. Available from: http://www.jmnn.org/text.asp?2014/3/2/94/131961
| Introduction|| |
Endocrine and metabolic problems have complicated the management of HIV infection.  Dyslipidemia, changes in fat distribution, and insulin resistance are increased with the advent of HAART, especially protease inhibitors (PIs).  AIDS has turned into a chronic disease , with a higher risk of atherosclerotic complications. , Main risk factors for metabolic abnormalities associated with HAART include treatment duration, more advanced stages of the disease, and use of drugs such as protease inhibitors. 
This study was carried out with the aim to (i) evaluate body composition and the metabolic effects of HAART and (ii) compare the above variables between different HAART regimens.
| Materials and Methods|| |
Design and subjects
This was a cross-sectional study analyzing the results of body composition and metabolic parameters in a total of 201 HIV-infected cases on HAART. HIV-infected patients on HAART for a minimum of 3 months were included in the study and formed the study population. Patients were categorized into those receiving 1 st line or 2 nd line ART according to National AIDS Control Organization, India guideline.  Detailed clinical examination and relevant investigations were done in all the patients. And known cases of type 2 diabetes mellitus, chronic renal or hepatic disease, congestive cardiac failure, and patients on lipid-lowering drugs, patients on drugs which are known to affect body mass composition like steroids or interferon treatment for hepatitis C were excluded.
Detailed history regarding the duration of HIV infection and the duration since the start of ART were taken in all the patients. And, history regarding presence of other co-infections like hepatitis B, hepatitis C, and other opportunistic infections were also noted. Detailed general physical and systemic examination was done. Routine investigations including fasting and post-prandial blood glucose, lipid profile, CD4 counts, and hemogram were performed. Diabetes mellitus was diagnosed based on American Diabetes Association (ADA) criteria. 
Body mass composition was analyzed in all the patients using segmental body composition monitor (Manufactured by TANITA, JAPAN).
All statistical calculations were performed with the SPSS 20 software. Comparisons between the groups were made with the paired t test where appropriate. The Pearson correlation with two-tailed probability values was used to estimate the strength of association between variables. The level of statistical significance was set at P ≤ 0.05. All results were expressed as mean ± SD.
| Results|| |
A total of 201 HIV-infected patients (142 were males and 59 were females) were included in the study. Majority of patients were on 1 st line ART (89.56%) as compared to 10.44% on second line ART. The distribution of cases based on sex and various regimens is shown in [Table 1]. Maximum numbers of patients were receiving the triple drug combination of stavudine, lamivudine, and nevirapine regimen. [Table 2] shows comparison of anthropometric and body compostion parameters between those on 1 st and 2 nd line ART. Over all 30.84% of patients had hemoglobin of < 10 gm%. Though the incidence of anemia was higher in patients on 2 nd line treatment, it did not show a statistically significant difference between 1 st line and 2 nd line treatment with a P value of 0.237.
|Table 1: Percentage of patients according to drug regimen and sex distribution|
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|Table 2: Comparison of diff erent characteristics between those on 1st line and 2nd line anti-retroviral therapy|
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The incidence of lipodystrophy was higher in patients on stavudine-based regimen. But, when groups are considered, its prevalence was more among 2 nd line group. However, lipodystrophy also did not show a statistically significant difference between the two groups and had a P value of 0.845 as shown in [Table 3].
|Table 3: Comparison of lipodystrophy between different anti-retroviral regimens|
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Among the patients on 1 st line treatment, 62.23% of patients had a normal BMI, 25% were underweight, and 12.77% were overweight. But, in 2 nd line group, maximum percentage of patients were in underweight group, 52.38% and only 9.53% were overweight with 39.09% having normal BMI. The abnormalities in body composition are shown in [Figure 1].
|Figure 1: The percentage of patients showing abnormal body mass composition on 1st and 2nd line anti-retroviral therapy|
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Similarly, though the incidence of dysglycemia and dyslipidemia was higher in patients on 2 nd line treatment, it failed to show a statistically significant difference between the two groups as shown in [Table 4].
|Table 4: The percentage of patients showing abnormal glucose levels on various drug regimen|
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| Discussion|| |
Use of anti-retroviral therapy, particularly thymidine analogue, has been associated with the occurrence of HIV-associated lipoatrophy. ,, Prospective randomized comparisons evaluating body composition changes among HIV-infected patients are limited. Prior investigators have reported central obesity and lipo-atrophy both prior to the initiation of anti-retroviral therapy  and with the use of HAART. 
Carr et al.  reported that 64% of patients receiving PIs had regional fat wasting and/or fat accumulation. Heath et al.  found a 50% prevalence of abdominal fat accumulation, 36% with peripheral wasting, and 6% with dorsocervical fat accumulation as self-reported by a population of 1035 (self-selected) participants.
In this cross-sectional study, comparing 1 st line ART with 2 nd line in HIV-infected patients who are on highly active anti-retroviral therapy (HAART), a decrease in all body composition parameters (i.e. BMI, total body fat, visceral fat, and subcutaneous fat) regardless of treatment assignment was noted. Development of lipoatrophy with a progressive loss of subcutaneous fat with increasing cumulative anti-retroviral exposure was observed. Diminished mitochondrial function has been proposed as causing lipoatrophy as well as a wide range of adverse events in HIV-infected persons taking NRTIs. However, the relationship between nucleoside analogues and lipoatrophy is confounded by the fact that NRTIs are not the only relevant cause of mitochondrial toxicity.  While the mechanism by which nucleoside analogues contribute to the syndrome of lipoatrophy has not been fully elucidated, differential effects with certain NRTI combinations have been reported.  Though stavudine has been claimed to produce significant lipodystrophy, other class of drugs can also produce the same. Nonetheless, this study is the first to assess the comparative effect of these 2 types of ART regimens in HIV-infected patients in India.
In a prospective study from North India, Gupta et al.  in 64 patients on HAART prior to initiation and 6 months later found that body mass index, waist circumference, total body fat, and lean body mass increased significantly. The total cholesterol, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol, triglyceride, and non-HDL-c increased significantly (P < 0.0001). Diabetes mellitus developed in 2.1% and metabolic syndrome in 19.1%.
Another study conducted in South Asia by Asha et al.  found that among patients receiving HAART, those with lipodystrophy had a greater degree of insulin resistance, higher triglyceride levels, and lower levels of high-density lipoprotein cholesterol. Also, Padmapriyadarsini et al.  concluded that significant decrease in triceps skin fold thickness, an increase in waist circumference and waist: hip ratio was observed more among females on HAART. Biometric impedance did not show any change in total body fat in either sex.
Saghayam et al.  conducted a prospective study of 190 HIV-infected patients who initiated a nevirapine-based HAART regimen. CD4 + T cell count, body weight, body mass index, anthropometry, and bioelectrical impedance data were collected prior to initiation of therapy, and after 6 months of therapy found that body weight increased by a mean of 2.8 kg (range, 12.5 to 22.5 kg), and CD4 + T cell counts increased by a mean of 140 cells/mm.  But, patients in all groups retained body shape symmetry and experienced no change in waist-to-hip ratio or regional body shape by anthropometry.
There is conflicting evidence on the impact of HAART on glucose metabolism. A series from Paris found that 79% of patients on HAART had abnormalities in glucose metabolism.  Behrens et al. found that 46% had impaired glucose tolerance and 13% frank diabetes.  While lipid parameters increased in both treatment arms in this study, there was no significant difference between the two statistically. Finally, a significant increase in blood glucose was noted in both the treatment arms compared to general population, which failed to show significance between two treatment groups.
Consistent with other studies, , there was a significant increase in fasting total cholesterol, LDL cholesterol, and triglycerides in both study arms. In one study, 75% of 90 subjects who had pre-PI lipid levels available had an increase in serum TGs after therapy. More than 50% had increases that warranted therapy.  These initial increases in lipid parameters may be related to an increase in body weight or improved immune function,  but the long-term effects of HAART on lipids have not been fully elucidated.
Waist-to-hip ratio (WHR) has been used as a marker of central obesity, which usually is accompanied by an increase in the waist circumference. However, in the present study, visceral fat was measured in kilograms using impedance technology. There has not been any previous study using this method for comparison. There was no significant difference between the two treatment arms.
In this study, Biometric impedance was used to assess body mass composition. Measurement of body composition in the clinical setting is hampered by the lack of a single method that is accurate, readily available, and affordable. Dual-energy x-ray absorptiometry (DEXA) is currently the most accepted laboratory technique for measuring body composition, because it is non-invasive, requires minimum efforts from the subjects, and is reliable. However, anthropometry performed in the study followed a standardized measurement protocols.
In summary, this cross-sectional study provides evidence of metabolic complications, lipodystrophy, and altered body mass composition with prolonged use of anti-retroviral therapy. But, the study failed to demonstrate any statistically significant difference between 1 st line and 2 nd line ART. However, this study highlights the importance of metabolic complications and the need for new agents not associated with these effects.
Limitations of the study
The number of patients on 1 st line therapy was 8 times more when compared to the 2 nd line group. Furthermore, body mass composition was not estimated by the gold standard method DXA scan. Frequent change in the regimen due to side-effects of drugs might have altered the results. And, the comparisons were not made in the same patients before and after therapy.
| References|| |
Dobs AS, Dempsey MA, Ladenson PW, Polk BF. Endocrine disorders in men infected with human immunodeficiency virus. Am J Med 1988;84:611-6.
Brown TT. Approach to the human immunodeficiency virus-infected patient with lipodystrophy. J Clin Endocrinol Metab 2008;93:2937-45.
Gir E, Vaichulonis CG, de Oliveira MD. Adhesion to anti-retroviral therapy by individuals with HIV/AIDS seenat an institution in the interior of São Paulo. [Article in Portuguese]. Rev Lat Am Enfermagem 2005;13:634-41.
Sadala ML, Marques Sde A. Twenty years of care for persons living with HIV/AIDS in Brazil: The health professionals' perspective. [Article in Portuguese]. Cad Saude Publica 2006;22:2369-78.
Barbaro G. Reviewing the cardiovascular complications of HIV infection after the introduction of highly active antiretroviral therapy. Curr Drug Targets Cardiovasc Haematol Disord 2005;5:337-43.
Yu PC, Calderaro D, Lima EM, CaramelliB. Hypolipidemic therapy under special conditions: Acquired immune deficiency syndrome. [Article in Portuguese]. Arq Bras Cardiol 2005;85 Suppl 5:58-61.
Friis-Møller N, Sabin CA, Weber R, d'ArminioMonforte A, El-Sadr WM, Reiss P, et al
.; Data Collection on Adverse Events of Anti-HIV Drugs (DAD) Study Group. Combination antiretroviral therapy and the risk of myocardial infarction. N Engl J Med 2003;349:1993-2003.
www.nacoonline.org. Antiretroviral therapy guidelines for HIV-infected adults and adolescents including post-exposure prophylaxis. 2007;Section A1-2:18-25.
American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2004;27 Suppl 1:S5-10.
WHO Expert Consultation. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet 2004;363:157-63.
Martinez E, Mocroft A, García-Viejo MA, Pérez-Cuevas JB, Blanco JL, Mallolas J, et al
. Risk of lipodystrophy in HIV-1-infected patients treated with protease inhibitors: A prospective cohort study. Lancet 2001;357:592-8.
Bernasconi E, Boubaker K, Junghans C, Flepp M, Furrer HJ, Haensel A, et al
.;Swiss HIV Cohort Study. Abnormalities of body fat distribution in HIV-infected persons treated with antiretroviral drugs: The Swiss HIV Cohort Study. J Acquir Immune Defic Syndr 2002;31:50-5.
Saint-Marc T, Partisani M, Poizot-Martin I, Bruno F, Rouviere O, Lang JM, et al
. A syndrome of peripheral fat wasting (lipodystrophy) in patients receiving long-term nucleoside analogue therapy. AIDS 1999;13:1659-67.
Kotler DP, Rosenbaum K, Wang J, Pierson RN. Studies of body composition and fat distribution in HIV-infected and control subjects. J Acquir Immune DeficSyndr Hum Retrovirol 1999;20:228-37.
Carr A, Samaras K, Chisholm DJ, Cooper DA. Pathogenesis of HIV-1 protease inhibitor-associated peripheral lipodystrophy, hyperlipidaemia, and insulin resistance. Lancet 1998;351:1881-3.
Heath KV, Hogg RS, Chan KJ, Harris M, Montessori V, O'Shaughnessy MV, et al
. Lipodystrophy-associated morphological, cholesterol and triglyceride abnormalities in a population-based HIV/AIDS treatment database. AIDS 2001;15:231-9.
Cossarizza A, Moyle G. Antiretroviral nucleoside and nucleotide analogues and mitochondria. AIDS 2004;18:137-51.
Gallant JE, Staszewski S, Pozniak AL, DeJesus E, Suleiman JM, Miller MD, et al
.; 903 Study Group. Efficacy and safety of tenofovir DF vsstavudine in combination therapy in antiretroviral-naive patients: A 3-year randomized trial. JAMA 2004;292:191-201.
Gupta V, Biswas A, Sharma SK. Metabolic and body composition changes after six months of highly active antiretroviral therapy in northern Indian patients. Int J STD AIDS 2011;22:46-9.
Asha HS, Seshadri MS, Paul TV, Abraham OC, Rupali P, Thomas N. Human immunodeficiency virus-associated lipodystrophy: An objective definition based on dual-energy x-ray absorptiometry-derived regional fat ratios in a South Asian population. Endocr Pract 2012;18:158-69.
Padmapriyadarsini C, Swaminathan S, Karthipriya MJ, Narendran G, Menon PA, Thomas BE. Morphologic and body composition changes are different in men and women on generic combination antiretroviral therapy: An observational study. J Assoc Physicians India 2010;58:375-7.
Saghayam S, Kumarasamy N, Cecelia AJ, Solomon S, Mayer K, Wanke C. Weight and body shape changes in a treatment-naive population after 6 months of Nevirapine-based generic highly active antiretroviral therapy in South India. Clin InfectDis 2007;44:295-300.
Vigouroux C, Gharakhanian S, Salhi Y, Nguyen TH, Chevenne D, Capeau J, et al
. Diabetes, insulin resistance and dyslipidaemia in lipodystrophic HIV-infected patients on highly active antiretroviral therapy (HAART).Diabetes Metab 1999;25:225-32.
Behrens G, DejamA, Schmidt H, Balks HJ, Brabant G, Körner T, et al
. Impaired glucose tolerance, beta cell function and lipid metabolism in HIV patients under treatment with protease inhibitors. AIDS 1999;13:F63-70.
Fontas E, van Leth F, Sabin CA, Friis-Møller N, Rickenbach M, d'ArminioMonforte A, et al
.; D: A: D Study Group. Lipid profiles in HIV-infected patients receiving combination antiretroviral therapy: Are different antiretroviral drugs associated with different lipid profiles? J Infect Dis 2004;189:1056-74.
Galli M, Ridolfo AL, Adorni F, Gervasoni C, Ravasio L, Corsico L, et al
. Body habitus changes and metabolic alterations in protease inhibitor-naive HIV-1-infected patients treated with two nucleoside reverse transcriptase inhibitors. J Acquir Immune Defic Syndr 2002;29:21-31.
Smith JH, Martin GJ, Decker CF. Hyperlipidemia associated with the use of protease inhibitors. Clin Infect Dis 2000;31:207-8.
Gervasoni C, Ridolfo AL, Trifirò G, Santambrogio S, Norbiato G, Musicco M, et al
. Redistribution of body fat in HIV-infected women undergoing combined antiretroviral therapy. AIDS 1999;13:465-71.
[Table 1], [Table 2], [Table 3], [Table 4]