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Long-Acting CAB Superior to Daily
Oral TDF/FTC in Preventing HIV in Women
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HIVR4P Virtual, January 27-28 and February 3-4, 2021
Mark Mascolini
Women receiving injected long-acting cabotegravir (CAB LA) every 8 weeks had an 89% lower risk of acquiring HIV infection than women taking daily oral tenofovir/emtricitabine (TDF/FTC), according to 3-year results of the 3200-woman HPTN 084 trial [1]. Both preexposure prophylaxis (PrEP) regimens were generally safe and well tolerated. The results support similar findings of superior HIV prevention with CAB LA than with TDF/FTC in men who have sex with men (MSM) [2].
HPTN 084 enrolled 3200 cisgender women from 18 to 45 years old at 20 sites in 7 African countries. Enrollees had to be HIV-negative, sexually active, using a reliable form of contraception, and not pregnant or breastfeeding. The trial randomized women to 5 weeks of oral CAB or placebo, or to oral TDF/FTC or placebo. Women in the CAB groups switched to long-acting injected cabotegravir (CAB LA) after week 5 and randomized follow-up was planned for up to 185 weeks (3.5 years).
A superiority analysis compared HIV incidence (the new-infection rate) during these randomized phases with intent-to-treat Cox proportional hazards models stratified by study site. Interim reviews were planned when researchers had 22%, 39%, 59%, and 78% of data. The trial crossed a prespecified stopping boundary at an interim review on November 5, 2020. This analysis involved 1614 women randomized to CAB LA and 1610 randomized to TDF/FTC.
Baseline factors were similar-often identical-in the CAB LA and TDF/FTC arms: Overall median age stood at 25 years, 82% of women were not living with a partner, 34% had an HIV-positive or status-unknown partner in the past month, 54% had 2 or more sex partners, 17% had Chlamydia trachomatis infection, 7% had gonorrhea, and 55% had a body mass index at or above 25 kg/m2 (the overweight threshold).
HPTN 084 researchers counted 40 infections over 3892 person-years of follow-up for a pooled HIV incidence of 1.03 per 100 person-years (1 infection in every 100 women followed for 1 year). So both PrEP agents strongly prevented HIV infection. But CAB and TDF/FTC differed in the high level of prevention they achieved:
There were 4 HIV infections in the CAB LA group and 36 in the TDF/FTC group. HIV incidence measured only 0.2 per 100 person-years in the CAB LA arm (confidence interval 0.06 to 0.52) versus 1.86 (confidence interval 1.3 to 2.57) in the TDF/FTC arm. Because of prespecified criteria, this large difference justified stopping the blinded phase of the trial. Women randomized to CAB LA had an 89% lower risk of HIV infection than women randomized to TDF/FTC.
Tenofovir plasma levels in a subset of 375 women showed that only 60% had a level above 40 ng/mL (indicating approximately daily use) at week 4. That proportion fell to 46% at week 9, 42% at week 17, 38% at week 33, and 34% at week 57. These results indicated that daily adherence to TDF/FTC started low and got lower as the trial continued. In contrast, 89% or more women randomized to CAB LA got their injection at 5 points up to 24 to 30 months of follow-up. Two people in the CAB LA group who became infected with HIV had not received CAB recently, whereas 2 had.
Injection site reactions arose in 25% of CAB LA participants with the first injection. That reaction rate fell to 8% with the second injection, 6% with the third injection, and 1% with the fourth, fifth, and sixth injection, then rebounded to 8% with the seventh injection. No one dropped out of the trial because of an injection site reaction. Through about 3 years of follow-up, women in the CAB LA group gained 2.4 kg/year, compared with 2.2 kg/year in the TDF/FTC group, a nonsignificant difference (P = 0.12).
At an HIVR4P press conference, researcher Sinead Delaney-Moretlwe rated every-2-month CAB LA injections as an intervention "achievable in the real world" since many women are used to routine contraceptive injections. She noted that results of this trial in cisgender women supplement findings of HPTN 083, which found 66% lower HIV incidence among MSM receiving CAB LA every 8 weeks than in those taking TDF/FTC daily [2].
References
1. Delany-Moretlwe S, Hughes JP, Bock P, et al. Long acting injectable cabotegravir is safe and effective in preventing HIV infection in cisgender women: interim results from HPTN 084. HIVR4P (HIV Research for Prevention) Virtual, January 27-28 and February 3-4, 2021. Abstract HY01.02.
2. National Institute of Allergy and Infectious Diseases. Long-acting injectable form of HIV prevention outperforms daily pill in NIH study. July 7, 2020. https://www.nih.gov/news-events/news-releases/long-acting-injectable-form-hiv-prevention-outperforms-daily-pill-nih-study
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