Long-acting injected cabotegravir given for preexposure prophylaxis (PrEP) of HIV did not induce weight gain in HIV-negative people in a 41-week placebo-controlled trial . Added pounds and wider waists have emerged as potential problems with other integrase inhibitors, especially in blacks and women. This analysis of cabotegravir is the first to closely explore weight changes with this investigational integrase inhibitor.
Researchers scrutinized data from HPTN 077, a phase 2 trial that randomized HIV-negative people to one of two cabotegravir doses or to placebo. The 199 participants lived in Brazil, Malawi, South Africa, and the United States. This analysis compared 134 people who got at least one cabotegravir dose with 43 who got placebo. After lead-in doses of oral cabotegravir or placebo, participants received either placebo or cabotegravir given by intramuscular injection. The cabotegravir dose was either 800 mg every 12 weeks or 600 mg every 8 weeks. The injection phase lasted from week 5 to 41.
Researchers measured participants' weight when they entered the study, at weeks 2 and 4 during the oral phase, and at weeks 5, 17, 19, 29 or 33, and 41 of the injection phase. They measured fasting glucose and fasting lipids at study entry and week 41.
The cabotegravir and placebo groups had young median ages of 29 and 34 (P = 0.04), two thirds of each group were women, about 40% black, 26% white, and 26% Hispanic. Current smokers made up only 9% of the cabotegravir group and 12% of the placebo group. Median initial body mass index (BMI) measured 26.6 with cabotegravir and 26.5 with placebo, meaning both groups were just a little overweight. Median weights in the two groups were 74.8 kg and 74 kg.
From week 0 to week 41, median weight inched up 1.1 kg with cabotegravir and 1.0 kg with placebo, a nonsignificant difference (P = 0.66). (One kg equals 2.2 pounds.) Most of these small weight gains occurred in the longer injection phase of the study (0.9 kg with cabotegravir and 0.7 kg with placebo, P = 0.65). Weight gains during the trial did not differ significantly with cabotegravir versus placebo in any subgroup analyzed: whites, blacks, Hispanics, men, women, BMI above or below 26.6 kg/m2, smokers, or the two cabotegravir dose groups.
Two of 4 people in the cabotegravir group who were underweight when the trial began (BMI below 18.5 kg/m2) attained normal weight by the end of the study. Among 50 cabotegravir takers with normal weight at study entry, 7 (14%) became overweight by study end. Among 34 initially overweight people taking cabotegravir, 4 (12%) became obese and 3 (9%) trimmed to normal weight. All 42 people obese when they started cabotegravir remained obese throughout the study.
Fasting glucose rose slightly through 41 weeks with both cabotegravir and placebo, and the difference between study arms was not significant. Total cholesterol, "bad" LDL cholesterol, and triglycerides all fell during the trial in both study groups, with no significant difference between groups.
The 41-week findings indicate that injected cabotegravir doses meant to last 8 or 12 weeks have little if any impact on weight of young HIV-negative people. HPTN 077 researchers suggested the weight gains seen in people taking integrase inhibitors for HIV infection could reflect (1) integrase inhibitor-HIV interactions, (2) nucleoside/nucleotide-integrase inhibitor interactions, or (3) bystander effects of other antiretrovirals. They noted, for example, that weight gains with integrase inhibitors have proved lower when the regimen includes tenofovir disoproxil fumarate (TDF) than when it contains tenofovir alafenamide (TAF), abacavir, or only the integrase inhibitor.
1. Landovitz RJ, Zangeneh SZ, Chau G, et al. Cabotegravir is not associated with weight gain in HIV-negative individuals: HPTN 077. Conference on Retroviruses and Opportunistic Infections (CROI). March 4-7, 2019. Seattle. Abstract 34LB.