Among women, HIV pre-exposure prophylaxis (PrEP) with injectable cabotegravir was superior to oral tenofovir diphosphate plus emtricitabine (TDF-FTC), according to results of a phase 3, randomized, double-blinded, double-dummy, active-controlled superiority trial, published in The Lancet.
The HPTN 084 study was conducted at 20 centers in 7 countries in sub-Saharan Africa. Women (N=3224) at increased risk for HIV infection who agreed to use long-acting reversible contraception were randomly assigned in a 1:1 fashion to receive HIV PrEP with either active cabotegravir with TDF-FTC placebo (n=1614) or cabotegravir placebo with active TDF-FTC (n=1610). The study was divided into 3 phases (oral, injection, and tail). In the oral phase, patients received either cabotegravir (30 mg) or TDF-FTC (300/200 mg) orally up to week 5. In the injection phase, patients received either cabotegravir (600 mg) or TDF-FTC (300/200 mg) intramuscular injections at weeks 5 and 9, and at 8-week intervals up to week 185 thereafter. In the tail phase, all patients received oral TDF-FTC daily for 48 weeks.
Among patients included in both treatment groups, the median age was 25 (IQR, 22-30) years, and 2 (0.1%) patients in the cabotegravir group self-identified as transgender men. Other baseline characteristics, including race/ethnicity, residing with a primary sexual partner, 2 or more sexual partners, and employment as a sex worker, were balanced between the patient groups.
At month 30, the rate of retention was 76.9% for patients in the cabotegravir group vs 90.9% for those in the TDC-FTC group.
Compared with TDC-FTC, cabotegravir was associated with an 88% decreased risk for HIV infection (adjusted hazard ratio, 0.12; 95% CI, 0.05-0.31; P <.0001). Of 4 patients diagnosed with HIV infection who received cabotegravir, post hoc analysis showed that 1 was infected at enrollment.
Among a random subset of patients who received TDF-FTC, fewer than half (41.9%) had plasma tenofovir concentrations consistent with daily use. Moreover, adherence became less consistent over time.
There were 29 confirmed pregnancies in the cabotegravir group vs 20 in the TDF-FTC group, and no congenital anomalies were reported. The incidence of chlamydia and gonorrhea infections was similar between treatment groups, occurring at rates of 19.6 and 7.7 per 100 person-years, respectively.
The incidence of adverse events was similar between the cabotegravir and TDC-FTC groups (92.1% vs 92.3%), and 33 patients in each group reported severe events. The most common events (>20%) were decreased creatinine clearance, increased creatinine, and gastrointestinal disorders. Of note, 15 and 18 patients in the cabotegravir and TDC-FTC groups prematurely discontinued treatment due to liver-related events, respectively.
This study was limited by the exclusion of women who were not using long-acting reversible contraception.
“Given the urgent need for an expanded range of effective options for HIV prevention in women, these data support the inclusion of injectable cabotegravir as an additional choice, particularly for women in high-incidence settings where the need is greatest,” the researchers concluded.
Disclosure: Multiple authors declared affiliations with industry. Please see the original article for a full list of disclosures.
Delany-Moretlwe S, Hughes JP, Bock P, et al. Cabotegravir for the prevention of HIV-1 in women: results from HPTN 084, a phase 3, randomised clinical trial. Lancet. 2022;S0140-6736(22)00538-4. doi:10.1016/S0140-6736(22)00538-4