Although the headline PrEP news at CROI 2015 went to the PROUD and IPERGAY studies (see reports above), important additional PrEP trials covered implementation and alternative dosing with oral PrEP and disappointing news that tenofovir gel was not effective in African women.
Raphael Landovitz set the context for the meeting in a plenary lecture about oral PrEP including implementation scale-up, especially the initially low but now increasing uptake in the US.1
This included reference to the difference pharmacokinetics of tenofovir and FTC with 10-100 fold higher tenofovir exposures in rectal compared to cervico-vaginal tissue. This suggests that the adherence requirement may be higher for women (6/7 doses/week) compared to men (when >4 doses/week still confers high level protection).
Referring to the heat map modelling by Abbas et al showed that the population effect on reducing infections seen in high effectiveness studies is not reduced even if risk behaviour increases,2 noting the risk compensation has not been reported from randomised PrEP trials, including in open-label studies.
Also drug resistance has generally been rare (~2% of infected, 0.06% of exposed) in studies with frequent clinic attendance, this is due to either sufficiently high adherence to protect against infection or sufficiently low adherence to not provide selective pressure. As expanded access to PrEP involves less frequent HIV testing in real life settings, monitoring is warranted for the higher risk of resistance from continuing (or returning) to use PrEP after occult HIV infection and prior to diagnoses (~25%).
The time for daily dosing to reach protective levels has been estimated as needing five days for men to reach 99% protection for rectal exposure (95% CI: 69% to 100%) and that after reaching steady state, protection might be maintained (in men) at >90% for seven days, but dramatically drops thereafter.3
In contrast, it is likely to take three weeks of daily dosing for women to reaching estimated protective levels.
Although side effect reports have been low in clinical studies, this is also in the context of low adherence and therefore much lower actual drug exposure.
This talk noted the tremendous potential for PrEP to become new options that HIV negative people can use to take control of their protection against HIV.
PrEP as a Bridge to ART in Serodifferent Couples
Jared Baeten from the University of Washington, presented important results from using short-term PrEP as a "bridge" by HIV negative partners in serodifferent couples until the HIV positive partner started ART, and for six months (or longer) after.4
The Partners Demonstration Project enrolled more than 1000 serodifferent high risk heterosexual couples in Kenya and Uganda between November 2012 and August 2014. Based on a population incidence of 5.3/100 person-years (95% CI: 3.2 to 7.6), approximately 20 new infections were expected.
However, up until July 2014, only one incident HIV infection was reported from 440 person-years of follow-up. This was an observed HIV incidence of 0.2/100 person-years (95% CI: 0.0 to 1.3), p<0.0001 vs predicted. During the 440 person-years of follow-up, PrEP was used 47% of the time, ART 17%, both 25%, and neither 11%.
The single transmission occurred with evidence of low PrEP adherence and in the absence of ART.
The potential benefit from PrEP as a bridge during the first six months of ART was also reported in a poster from the Partners PrEP study, based on transmission risks during three periods: (1) after diagnosis while eligible for ART but not on ART; (2) during the first six months that the positive partner was on ART; and (3) when the positive partner had been on ART for >6 months.5
During 510 person-years of follow-up for negative partners in periods 1, (175 PY), 2 (168 PY) and 3 (167 PY), there were 3 phylogenetically linked HIV infections in each of groups 1 and 2 and no HIV infections in group 3. The numbers of sex acts was roughly comparable between groups, as was the generally high reported use of condoms (~90-92% of times).
HIV incidence (95% CI) was 1.71 (0.35 to 5.01), 1.79 (0.37 to 5.22) and 0.00 (0.00 to 2.20) per 100 person-years, in groups 1, 2 and 3, respectively.
Details were not provided on whether unlinked infections occurred, although PrEP in the pre-ART and early ART periods would also provide protection from other partners.