Changes in Waist Circumference in HIV-Infected Individuals Initiating a Raltegravir or Protease Inhibitor Regimen: Effects of Sex and Race

Abstract

Background This study investigates the association of clinical and demographic predictors with abdominal fat gain, measured using waist circumference (WC) and self-reported abdominal size. Methods We analyzed data from ACTG A5257, a clinical trial that randomized treatment-naïve HIV-infected participants to 1 of 3 antiretroviral regimens: raltegravir (RAL) or the protease inhibitors (PIs) atazanavir/ritonavir (ATV/r) or darunavir/ritonavir (DRV/r), each in combination with tenofovir disoproxil fumarate/emtricitabine. Associations of treatment and baseline/demographic characteristics with 96-week WC change were assessed using repeated-measures models. Ordinal logistic regression was used to examine the associations of predictors with week 96 self-reported abdominal changes. Results The study population (n = 1809) was 76.0% male and predominantly black non-Hispanic (41.9%) and white non-Hispanic (34.1%). Mean baseline WC was 90.6 cm, with an average 96-week increase of 3.4 cm. WC increases were higher in the RAL arm compared with DRV/r (P = .0130). Females experienced greater increases in WC on RAL vs ATV/r than males (P = .0065). Similarly, a larger difference in WC change was found for RAL vs DRV/r for black vs nonblack individuals (P = .0043). A separate multivariable model found that in addition to the treatment regimen, higher baseline viral load and lower CD4+ were also associated with WC increases. Conclusions With antiretroviral therapy initiation, higher WC increases in the RAL arm compared with PIs were more pronounced in female and black participants, and a more advanced baseline HIV disease state was a strong predictor of larger abdominal increases. Understanding factors predisposing individuals to abdominal fat gain could inform health management after therapy initiation.

Weight gain before and after switch from TDF to TAF in a U.S. cohort study

“…However, the similarities in weight change observed across core groups do raise questions as to the role of concurrent switches to TAF in weight changes reported with switches to InSTI. Finally, the estimated weight loss over time on TDF observed in OPERA among PLWH who maintained raltegravir did not align with the literature suggesting weight gain with raltegravir even without TAF use [25,26,[35][36][37]. However, this may reflect an age-related decline in weight, as raltegravir was prescribed to an older population.…”

“…The marked increase in weight immediately following TAF initiation observed in OPERA was in line with results in ART-na€ ıve PLWH in clinical trials [10,12] and in the CFAR Network of Integrated Clinical Systems (CNICS) cohort [31]. While multiple studies have shown greater weight gains with InSTI-based regimen overall [11,12,[17][18][19][20][21][22][23][24][25][26] or specifically with dolutegravir, bictegravir or raltegravir [10][11][12]18,19,22,[25][26][27][28][29][30][31][35][36][37] compared to other regimens, most did not account for the role of TAF. In OPERA, the estimated rates of weight gain were numerically slightly higher in the first nine months of TAF when maintaining an InSTI, elvitegravir/cobicistat or dolutegravir, and when switching to bictegravir or dolutegravir, although differences between groups were not tested directly, and confidence intervals overlapped.…”

Human Immunodeficiency Virus (HIV) and Aging: Multimorbidity in Older People With HIV in One Nonurban Southeastern Ryan White HIV/AIDS Program Clinic

“…In Cohort 2, women were more than twice as likely as men to have multimorbidity. Other studies have documented a higher prevalence of obesity among women, particularly in those on ART regimens containing tenofovir alafenamide and integrase strand inhibitors, especially dolutegravir and bictegravir [ 30 , 31 ]. We did not collect data on the specifics of the ART regimen for the participants; however, it is possible that participants in Cohort 2 were prescribed regimens associated with increases in weight that disproportionately affect women.…”

“…Given the lower rate of multimorbidity for those with private insurance, which was likely related to better access to non-HIV preventative care, the RWHAP should consider a targeted investment to deliver more preventative care in RWHAP clinics with the goal of reducing multimorbidity prevalence in PWH. This is especially important given the growing evidence about the impact of HIV and ART on cardiovascular risk and weight gain [ 4 , 30 , 31 ]. The higher rate of multimorbidity in women in the aging PWH population should be investigated further, and RWHAP Part D should consider expanding their support for this population’s non-HIV care.…”

The Relationship Between Body Mass Index and Inflammatory Parameters in HIV Patients Treated with Antiretrovirals

“…Specific ART regimens or drug classes have also been implicated in weight gain, with integrase strand transfer inhibitors (INSTIs) cited in 2 randomized studies [5] and several retrospective cohort studies [6]. Highly active antiretroviral therapy (HAART)-induced lipoatrophy, currently the most common form of lipoatrophy worldwide, is associated with hypoleptinemia, insulin resistance, and elevated triglycerides in the context of the HAART-induced metabolic syndrome (HAART-MS) [7].…”