Systematic Review of Antiretroviral-Associated Lipodystrophy: Lipoatrophy, but Not Central Fat Gain, Is an Antiretroviral Adverse Drug Reaction

Abstract

BackgroundLipoatrophy and/or central fat gain are observed frequently in patients on antiretroviral therapy (ART). Both are assumed to be antiretroviral adverse drug reactions.MethodsWe conducted a systematic review to determine whether fat loss or gain was more common in HIV-infected patients on ART than in uninfected controls; was associated with specific antiretrovirals; and would reverse after switching antiretrovirals.ResultsTwenty-seven studies met our inclusion criteria. One cohort study reported more lipoatrophy, less subcutaneous fat gain, but no difference in central fat gain in HIV-infected patients on ART than in controls. Randomised controlled trials (RCTs) showed more limb fat loss (or less fat gain) with the following regimens: stavudine (versus other nucleoside reverse transcriptase inhibitors (NRTIs)); efavirenz (versus protease inhibitors (PIs)); and NRTI-containing (versus NRTI-sparing). RCTs showed increased subcutaneous fat after switching to NRTI-sparing regimens or from stavudine/zidovudine to abacavir/tenofovir. There were no significant between-group differences in trunk and/or visceral fat gain in RCTs of various regimens, but results from efavirenz versus PI regimens were inconsistent. There was no significant between-group differences in central fat gain in RCTs switched to NRTI-sparing regimens, or from PI-containing regimens.ConclusionsThere is clear evidence of a causal relationship between NRTIs (especially thymidine analogues) and lipoatrophy, with concomitant PIs possibly having an ameliorating effect or efavirenz causing additive toxicity. By contrast, central fat gain appears to be a consequence of treating HIV infection, because it is not different from controls, is not linked to any antiretroviral class, and doesn't improve on switching.

Determinants of body mass index by gender in the Dikgale Health and Demographic Surveillance System site, South Africa

“…In South Africa, evidence suggests a decline in the use of over the counter cigarettes probably due to increased taxation, but there is a shift towards the use of ‘roll your own’ cigarettes particularly in rural areas [61]. A lower BMI in treatment naïve HIV infected people, is likely due to disease associated cachexia [62], while a lower BMI in those on treatment may result from lipoatrophy caused by antiretroviral medication [63]. …”

Body composition in the Study of Women Entering and in Endocrine Transition (SWEET): A perspective of African women who have a high prevalence of obesity and HIV infection

“…Our data from both ANOVA and multiple regression analysis demonstrate a negative relationship of ART with both total body fat and BMC. In a recent systematic review of the lipodystrophic effects of ART it was shown that the use of antiretroviral agents is associated with lipoatrophy, and thus lower BMI [47]. Studies have also shown that ART is associated with reduced bone mass [48].…”

Structural and Preclinical Studies of Computationally Designed Non-Nucleoside Reverse Transcriptase Inhibitors for Treating HIV infection

“…Furthermore, efavirenz's low genetic barrier to resistance requires high-level adherence to therapy for efficacy (Delaugerre et al, 2001;Riddler et al, 2008). HIV-infected patients receiving efavirenz also suffer from side effects such as depression, insomnia, skin rash, lipodystrophy, and lipoatrophy (Riddler et al, 2008;de Waal et al, 2013). On the other hand, rilpivirine prescription requires a heightened vigilance in clinical practice due to its unfavorable interaction with acid suppressant medication (Janssen et al, 2005;Rathbun and Liedtke, 2011).…”