Daily, on-demand PrEP regimens prevent HIV in MSM

Both daily and on-demand regimens of pre-exposure prophylaxis (PrEP) with tenofovir/emtricitabine (TDF/FTC) strongly suppress the rates of HIV infection among men who have sex with men (MSM), according to a study presented at the 2021 Conference on Retroviruses and Opportunistic Infections (CROI 2021).

At the same time, both dosing schedules also show good safety profiles, triggering low rates of adverse events (AEs) and discontinuations.

The researchers conducted an open-label prospective cohort study in the Paris region, enrolling 3,067 adults (median age, 36 years) who were HIV negative at baseline, but were deemed to be high-risk due to inconsistent condom use. Participants were allowed to choose their dosing regimen (daily vs on-demand PrEP) and were also given the freedom to switch.  

Follow-ups were conducted every 3 months, and infection status was assessed using a fourth-generation enzyme linked immunosorbent assay HIV test.

Almost all participants (98.5 percent; n=3,022) were MSM; only 31 identified as heterosexual. Dosing preference was highly balanced, with 49.5 percent and 50.5 percent of participants choosing on-demand and daily PrEP, respectively. At baseline, there was a significantly higher proportion of MSM in the former regimen (p=0.0002), while those who opted for the latter reported significantly more sexual partners in the last 3 months (p<0.0001). [CROI 2021, oral abstract 148]

Over a mean follow-up of 22.1 months (5,633 person-years), only six cases of HIV were documented, resulting in a global incidence rate of 0.11 per 100 person-years.

Disaggregating the results revealed no significant difference between the two dosing regimens. Both on-demand and daily TDF/FTC PrEP led to an HIV incidence rate of 0.12 per 100 patient-years (incidence rate ratio [IRR], 0.99, 95 percent confidence interval [CI], 0.13–7.38).

When using a previously published HIV incidence rate of 6.6 percent among placebo recipients, the current intervention was able to avert 361 infections. [N Engl J Med 2015;373:2237-2246]

In terms of safety, the researchers recorded 152 drug-related AEs in the daily dosing regimen, and 192 in the on-demand group, suggesting that the former was slightly safer (IRR, 0.78, 95 percent CI, 0.63–0.97). In both regimens, gastrointestinal AEs were the most common, followed by asthenia and headaches.

There were also reports of serious AEs: 92 in the daily and 77 in the on-demand regimens (IRR, 1.18, 95 percent CI, 0.86–1.62). These were mostly infections, though there were also 16 total cases of neuro-psychiatric AEs.

Sixteen patients discontinued treatment due to drug-related AEs, nine of whom were taking on-demand PrEP. Most of the discontinuations were temporary; only three permanently terminated PrEP due to gastrointestinal side effects. One death was recorded, and the cause was suicide.