In people living with HIV, ART treatment with regimens containing integrase inhibitors (INIs) has been associated with weight gain and increased waist circumference, raising concerns about possible future risk for metabolic and cardiovascular disease. These changes have been associated with female sex, non-white individuals, and those with higher baseline BMI. HPTN 077, a Phase 2a randomized placebo-controlled study of two dose/dose-interval regimens of cabotegravir, enrolled HIV-uninfected participants from 8 sites in the US (4), Brazil (1), and sub-Saharan Africa (3). 199 participants were enrolled and randomized 3:1 to active CAB or placebo and received oral CAB 30mg or placebo (PBO) QD x 4 weeks, a one-week washout, and then sequential injections of CAB LA or 0.9% saline PBO from Week (W) 5 through W41.
We measured weight at study entry (W0), during oral study product administration (W2, W4) and during injectable study product administration (W5, 17, 19, 29/33, and 41). Age, race/ethnicity, sex at birth, injectable dosing cohort, smoking status, and BMI were assessed at baseline. Longitudinal models fitted via generalized estimating equations (GEE) were used to assess marginal effects of study arm on weight over time. Wilcoxon rank sum tests were used to compare medians of numeric variables and chi-square tests were used to compare frequencies of categorical variables.
The Table shows median weights at W0 and W41 overall, and changes from baseline (W0-W41) by covariates of interest. Median weight change over 41 weeks was +1.1 kg (IQR -0.9, 3.0) in the CAB arm and +1.0 kg (IQR -1.2, 3.2) in the PBO arm (p=.66). In longitudinal statistical analyses, no statistically significant differences were found in change in weight from W0 to 41 in CAB vs. PBO treated participants in aggregate, by sex, dosing cohort, age, race/ethnicity, smoking status, BMI, nor by baseline BMI category. No differences in weight change for CAB vs. PBO were seen for W0-4 and W5-41 separately.
In this moderately sized global cohort of 199 HIV-uninfected males and females, there was no difference in weight change for participants receiving CAB compared to PBO-treated participants. Although structurally similar to dolutegravir, CAB may have different effects on weight/weight gain, or the interaction between HIV-infection and INI treatment may be an important contributor to observed weight gain as part of ART.