Clinical Pearls & Morning Reports
Landovitz et al. conducted a phase 3, randomized, double-blind, double-dummy trial that compared long-acting injectable cabotegravir (CAB-LA) with oral tenofovir disoproxil fumarate–emtricitabine (TDF–FTC) for human immunodeficiency virus (HIV) prevention in at-risk cisgender men and transgender women who have sex with men. Read the NEJM Original Article here.
Q: What is the potential contribution of cabotegravir to the preexposure prophylaxis of HIV?
A: Safe and effective long-acting injectable agents for preexposure prophylaxis (PrEP) for HIV infection are needed to increase the options for preventing HIV infection. Despite the availability of highly effective strategies for the prevention of HIV infection, the number of new infections worldwide continues to exceed 5000 per day. Daily oral TDF–FTC has been reported to provide protection against HIV infection across various populations. The efficacy of oral PrEP agents is directly correlated with adherence to prescribed dosing. PrEP agents that do not require regular or planned oral dosing may increase acceptability and protection during periods of risk, thereby reducing the risk of HIV acquisition.
Q: What kind of drug is CAB-LA?
A: CAB-LA is an integrase strand-transfer inhibitor that is administered as an intramuscular injection into the gluteus muscle. CAB-LA has potent anti-HIV activity, protects nonhuman primates from a broad range of HIV exposure types, and is generally safe, without limiting toxic effects, in humans.
A: Although TDF–FTC is known to be effective in preventing HIV infection when adherence is high, the authors found that the risk of HIV infection was lower by 66% in the cabotegravir group than in the TDF–FTC group in the prespecified analysis, a result that showed the superiority of CAB-LA to TDF–FTC. This finding was similar in magnitude and direction in key populations that have lower reported rates of adherence to daily oral PrEP agents, including Black men who have sex with men in the United States, transgender women, and participants younger than 30 years of age.
A: In a post hoc analysis, a mean annualized increase in body weight of 1.23 kg per year (95% CI, 1.05 to 1.42) was noted in the cabotegravir group, as compared with an increase of 0.37 kg (95% CI, 0.18 to 0.55) in the TDF–FTC group. Differences in weight change between the groups were observed primarily in the first 40 weeks of participation and were similar in the two groups later in the trial.