Raphael J. Landovitz
The novel integrase inhibitor cabotegravir — which is currently in development for both HIV prevention and treatment — was not associated with excess weight gain in HIV-uninfected patients compared with placebo, according to a recent study.
“ART that contains an integrase inhibitor has been associated with weight gain and increased waist circumference, with changes of greater magnitude seen among women, black patients, and those with lower CD4 and higher HIV RNA prior to starting ART,” Raphael J. Landovitz, MD, MSc, associate professor of medicine at the Center for Clinical AIDS Research and Education at the University of California, Los Angeles, and colleagues wrote. “Cabotegravir (CAB) is available both as an oral tablet for daily administration (being developed only for lead-in to the injectable product) and as a long-acting suspension for monthly or every-other-month intramuscular injection. Weight changes for HIV-infected participants in trials of CAB as part of combination ART have not yet been published.”
To examine these potential weight changes, researchers performed a post-hoc analysis of the phase 2 HPTN 077 study, in which 199 HIV-uninfected participants were randomly assigned in a 3:1 ratio to receive CAB or placebo.
The researchers said the study “provides a unique opportunity to evaluate changes in weight and metabolic parameters among participants exposed to long-acting injectable CAB or a placebo, absent HIV infection or additional antiretroviral agents.”
During the treatment course, participants received a daily oral tablet for 4 weeks, took a 1-week hiatus, and then received a series of injections, with a primary safety and tolerability endpoint after 41 weeks. The researchers enrolled two dose cohorts sequentially, the first with an injection phase consisting of three quarterly injections of 800 mg of CAB or placebo, and the second with five total injections of 600 mg of CAB at 8-week intervals after a 4-week initial separation.
Weight was measured at study entry, during the oral dosing phase at weeks 2 and 4, and during the injectable phase at weeks 5, 17, 19, 29 or 33, and 41.
Results of the study showed that among the 146 participants with paired weight measurements, between baseline and week 41, there was a median increase of 1.1 kg in weight for CAB-treated participants and 1 kg for placebo-treated participants. According to the study, a 5% or more increase in weight between baseline and week 41 was seen in 24 CAB recipients and seven placebo recipients. The researchers found that the distribution of weight changes across the 41-week treatment period did not differ between the two groups or when divided into the oral or injection phases.
“These results suggest that the observed excess weight increases for [integrase inhibitor]-treated HIV-infected individuals may be attributable to an interaction between integrase inhibitors and HIV itself or its inflammatory milieu — and/or an interaction between integrase inhibitors and other anti-HIV agents,” the researchers concluded. – by Caitlyn Stulpin
Disclosures: Landovitz reports receiving personal fees from Gilead Sciences, Merck and Roche. Please see the study for all other authors’ relevant financial disclosures.