Long-term daily PrEP with FTC/TAF highly effective for HIV prevention

Long-term daily oral pre-exposure prophylaxis (PrEP) with emtricitabine (FTC) plus tenofovir alafenamide (TAF) was found to be effective and well tolerated for HIV prevention, with treatment adherence observed through 144 weeks. These findings were published in The Lancet HIV.

To evaluate adherence and resistance trends associated with long-term daily oral PrEP use, researchers conducted a 48-week open-label extension study of a randomized, controlled phase 3 trial (ClinicalTrials.gov Identifier: NCT02842086). The analysis included cisgender men and transgender adult women who have sex with men who were enrolled across 94 sites in Europe and North America between September 2016 and June 2017. Patients in the phase 3 trial were randomly assigned 1:1 to receive either FTC plus tenofovir disoproxil fumarate (TDF; n=2693) or FTC/TAF (n=2694) daily for 96 weeks with matched placebo. After completion of the trial, 3699 patients participated in the open-label extension phase. The primary outcomes were HIV incidence among patients initially assigned to the FTC/TAF group, treatment adherence and genotypic resistance those diagnosed with HIV, and safety.

A total of 2115 (79%) patients initially assigned to FTC/TDF switched to FTC/TAF during the open-label extension phase of the study, whereas 2070 (77%) of those initially assigned to FTC/TAF continued with the same regimen.

During 15,817 person-years of follow-up, 27 patients were diagnosed with HIV infection across both study periods, with 3 diagnoses occurring in the open-label phase. Overall, 63% of the HIV diagnoses occurred among patients initially assigned to FTC/TDF and 37% occurred among those initially assigned to FTC/TAF.

Among patients who received FTC/TAF for at least 144 weeks, the rate of HIV infection was less than 1% (incidence rate [IR], 0.13 per 100 person-years; 95% CI, 0.061-0.23). During the open-label extension period, the researchers observed low rates of infection in both FTC/TAF recipients (IR, 0.093 per 100 person-years; 95% CI, 0.011-0.34) and FTC/TDF recipients (IR, 0.046 per 100 person-years; 95% CI, 0.0012-0.25).

Further analysis of the 27 patients diagnosed with HIV showed that 19% had unrecognized infections at baseline. Among the remaining 22 patients who developed HIV infection, 8 discontinued PrEP at least 30 days before HIV diagnosis, 13 discontinued PrEP within 30 days of diagnosis or had TDF concentrations consistent with low adherence prior to diagnosis, and 1 had an unknown TDF concentration. Of 23 patients with available plasma samples for retrospective analysis, 17% had detectable HIV RNA at the visit prior to diagnosis.

No tenofovir or emtricitabine resistance-associated mutations were observed among patients who discontinued PrEP at least 30 days before diagnosis or among those who demonstrated low treatment adherence.

In the safety analysis of patients who received up to 144 weeks of FTC/TAF, 94% reported treatment-emergent adverse event (AEs), 3% experienced grade 3 or 4 treatment-emergent AEs, and less than 1% experienced severe study drug-related AEs. The most common treatment-emergent AEs among the cohort included anal chlamydia (38%), oropharyngeal gonococcal infection (37%), proctitis gonococcal infection (34%), and exposure to communicable disease (24%). The researchers noted grade 3 or 4 laboratory abnormalities in 14% of patients, the most common of which were increased levels of aspartate aminotransferase (3%), low-density lipoprotein cholesterol while fasting (3%), and amylase (3%).

Study limitations include the inability to confirm HIV status in patients with suspected infection due to the lack of baseline plasma samples, the open-label design, potential retention bias, and potential low generalizability to other populations.

According to the researchers, “These data support the safety and efficacy of long-term PrEP using emtricitabine plus tenofovir alafenamide and show no evidence of delayed HIV-1 seroconversion with its use as daily oral PrEP.”

Disclosure: This study was supported by Gilead Sciences, and multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

By Jessica Nye, PhD

References:

Wohl DA, Spinner CD, Flamm J, et al. HIV-1 infection kinetics, drug resistance, and long-term safety of pre-exposure prophylaxis with emtricitabine plus tenofovir alafenamide (DISCOVER): week 144 open-label extension of a randomised, controlled, phase 3 trial. Lancet HIV. Published online July 12, 2024. doi:10.1016/S2352-3018(24)00130-9