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Although preexposure prophylaxis (PrEP) is a vital tool to prevent HIV infection, the effectiveness of oral PrEP directly correlates with adherence. In two papers, researchers now report on the HIV Prevention Trials Network 083 trial in which they assessed cabotegravir (CBV; a long-acting injectable integrase inhibitor not yet FDA-approved for PrEP) compared with oral tenofovir disoproxil fumarate–emtricitabine (TDF-FTC) in 4566 high-risk cisgender men and transgender women who have sex with men. Participants were randomized to TDF-FTC daily or long-acting injectable CBV every 8 weeks after a lead-in with daily oral CBV.
By 153 weeks, 39 participants in the TDF-FTC arm had acquired HIV versus 13 in the CBV arm — a 66% risk reduction with CBV. Injection-site reactions (ISRs) with injectable CBV were common (81%), but associated discontinuation was rare (2%). Of the 13 new HIV infections in the CBV arm, one was determined on reassessment to represent baseline infection, five were not proximate to CBV exposure, three occurred during the lead-in phase, and four occurred in participants receiving CBV injections. Among these latter seven cases, four had integrase resistance mutations (at least two of which were acquired after continued exposure to study drug). The single participant without resistance had subtherapeutic levels of CBV during lead-in therapy; all others had sufficient CBV levels. Among the 39 with new infection on TDF-FTC, 37 had inadequate tenofovir levels.
An additional finding was that diagnosis of new HIV infection was hampered by delays in detection of baseline or incident infection using antigen/antibody testing; such delays were more common (and longer) in the CBV arm (mean delay, 98 vs. 31 days). Retrospective analysis indicated that HIV RNA testing would have detected infections earlier in nearly all cases affected by delayed diagnosis.
Landovitz RJ et al. Cabotegravir for HIV prevention in cisgender men and transgender women. N Engl J Med 2021 Aug 12; 385:595. (https://doi.org/10.1056/NEJMoa2101016)
Marzinke MA.Characterization of human immunodeficiency virus (HIV) infection in cisgender men and transgender women who have sex with men receiving injectable cabotegravir for HIV prevention: HPTN 083. J Infect Dis 2021 Mar 19; [e-pub]. (https://doi.org/10.1093/infdis/jiab152)
Comment
Long-acting therapies for HIV are poised to change the landscape of care. For PrEP, several other agents also hold promise (with results in cisgender women anticipated). The opportunity to increase individual agency, decrease stigma, improve adherence, and overcome barriers to care is exciting. While this success of CBV is remarkable, the study also highlights the need to investigate other early-detection strategies such as screening with HIV RNA testing. All told, however, long-acting preventive strategies hold promise that many of us never before imagined.