The Impact of Weight Gain During HIV Treatment on Risk of Pre-diabetes, Diabetes Mellitus, Cardiovascular Disease, and Mortality

Abstract

Since the introduction of combined antiretroviral therapy (cART) and more effective treatments for AIDS, there has been a dramatic shift from the weight loss and wasting that characterised HIV/AIDS (and still does in countries where cART is not readily available or is initiated late) to healthy weight, or even overweight and obesity at rates mirroring those seen in the general population. These trends are attributable to several factors, including the “return to health” weight gain with reversal of the catabolic effects of HIV-infection following cART-initiation, strategies for earlier cART-initiation in the course of HIV-infection which have prevented many people living with HIV-infection from developing wasting, in addition to exposure to the modern obesogenic environment. Older cART regimens were associated with increased risk of body fat partitioning disorders (lipodystrophy) and cardiometabolic complications including atherothrombotic cardiovascular disease (CVD) and diabetes mellitus. Whilst cART now avoids those medications implicated in causing lipodystrophy, long-term cardiometabolic data on more modern cART regimens are lacking. Longitudinal studies show increased rates of incident CVD and diabetes mellitus with weight gain in treated HIV-infection. Abdominal fat gain, weight gain, and rising body mass index (BMI) in the short-term during HIV treatment was found to increase incident diabetes risk. Rising BMI was associated with increased risk of incident CVD, however the relationship varied depending on pre-cART BMI category. In contrast, a protective association with mortality is evident, predominantly in the underweight and in resource-poor settings, where weight gain reflects access to cART and virological suppression. The question of how to best evaluate, manage (and perhaps constrain) weight gain during HIV treatment is of clinical relevance, especially in the current climate of increasingly widespread cART use, rising overweight, and obesity prevalence and growing metabolic and cardiovascular disease burden in people living with HIV-infection. Large prospective studies to further characterise the relationship between weight gain during HIV treatment and risk of diabetes, CVD and mortality are required.

Vascular function and cardiovascular risk in a HIV infected and HIV free cohort of African ancestry: baseline profile, rationale and methods of the longitudinal EndoAfrica-NWU study

“…The increasing use of ART and the global obesity epidemic will likely accelerate the growing issues of weight gain, obesity, diabetes and CVD in PLHIV [34]. Although waist circumference did not differ between the HIV infected and HIV free participants in our study, the body mass index was lower (26 vs 29 kg/m 2 ) among those infected (79.9% on ART).…”

Real-World Assessment of Weight Change in People with HIV-1 After Initiating Integrase Strand Transfer Inhibitors or Protease Inhibitors

“…12 Differences in weight gain between regimens may be related to "return-to-health," a common phenomenon in PLWH. 16,22 However, our cohorts were well matched on demographic/clinical variables and only 2% to 3% were underweight at baseline. Additionally, this study only included the last follow-up weight/BMI measures that were ≥90 days post-index, whereas return-to-health is most likely to occur shortly after ARV initiation.…”

Weight Gain Following Initiation of Antiretroviral Therapy: Risk Factors in Randomized Comparative Clinical Trials

“…Possible mechanisms for ART-associated weight gain include a return-to-health phenomenon, especially in those with advanced human immunodeficiency virus (HIV) disease, with weight returning to a preillness baseline. The mechanism underlying the return-to-health phenomenon is incompletely understood, but likely results from the alleviation of HIV-associated inflammation and accelerated catabolism [ 12 ]. Treatment of HIV may also hasten resolution of opportunistic infections and gastrointestinal (GI) dysfunction that could adversely affect appetite and nutrient absorption.…”