- Category: Pre-exposure Prophylaxis (PrEP)
- Published on Tuesday, 16 July 2013 00:00
- Written by Gus Cairns
A pair of late-breaker presentations at the 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2013) this month in Kuala Lumpur provided new data about 2 studies of pre-exposure prophylaxis (PrEP) for injecting drug users and men who have sex with men and transgender women.
Adherence Levels, Efficacy, and Risk in the Bangkok Tenofovir Study
Michael Martin from the U.S. Centers for Disease Control and Prevention gave additional data filling out the results of the Bangkok Tenofovir Study of tenofovir-based PrEP for injecting drug users in Bangkok, Thailand.
The main results from this trial were published in June. The study found 49% fewer HIV infections among participants taking tenofovir compared with those receiving placebo. The study lasted longer than initially anticipated because both risk behavior and HIV incidence were far lower than expected, so results took longer to accrue.
Martin gave more data on adherence in the trial. The majority of participants in this study elected to take their daily tenofovir or placebo dose as directly observed therapy (DOT) at their treatment center.
Efficacy was 71% among DOT participants, who took their study drug on more than 70% of days, with no more than 2 consecutive days off. In terms of drug levels, efficacy was 70% among participants with detectable tenofovir levels when it was measured in their blood, compared with only 23% for people with undetectable tenofovir levels.
Efficacy increased with higher adherence levels. Among participants with 67% adherence as measured by drug levels, efficacy was 54%; with 90% adherence, it rose to 68%; with 95% adherence, 72%; and with 98% adherence, 84%.
One interesting aspect of the study was that there was no difference in HIV infection rates between tenofovir and placebo recipients for the first 3 years of the study; they only started to diverge after that. Martin commented that this may just have been a statistical fluke: incidence was so low that 3 or 4 more infections in the placebo arm would have made the arms diverge from the start.
There is another possibility, though: did the arms diverge because in the early phase of the trial people were more often sharing needles and tenofovir was not effective against needle-spread infections, and only started to become effective when the level of needle-sharing went down sufficiently to make sexual infections predominate?
In a commentary on the publication of the trial results in The Lancet, Salim Abdool Karim of the CAPRISA 004 microbicide trial team commented that the Bangkok trial could not give a firm answer as to whether PrEP worked against parenteral (injected) HIV infections. This remark has been interpreted as backing up the criticism of the original decision that participants could not be provided with clean needles, as free supply of these is illegal in Thailand. They can, however, be bought cheaply at pharmacies, and needle-sharing fell from 18% of all participants at baseline to 3% during the study.
Martin's team gave a partial answer to this in a poster that looked at associations between risk behaviors and HIV infections. They found that only 3 risk factors were significantly associated with HIV seroconversion in a multivariate analysis. Sharing needles was associated with a 8.9-fold greater risk of infection, having been in prison with a 2.7-fold higher risk, and being under age 30 (compared with over 30) with a 1.9-fold higher risk.
In contrast, no sexual risk factor was significantly associated with seroconversion. Needle-sharing remained by far the most significant risk factor throughout the study, so the infections seen are likely, in the main, to be due to needles, which should imply that the reductions seen in incidence in the tenofovir arm were due to reductions in needle-spread infections.
Recruitment, Retention, and Adherence in iPrEx-OLE
Bob Grant from the iPrEx study team provided the first data from iPrEx-OLE, where OLE stands for Open-Label Extension.
In this study, participants in the original placebo-controlled iPrEx study -- which reported an overall efficacy of 44% for tenofovir/emtricitabine (Truvada) PrEP -- were invited to join an extension study in which they all received open-label tenofovir/emtricitabine. The hope was that, if people knew they were not taking a placebo, adherence and therefore efficacy might be higher.
The efficacy results for iPrEx-OLE will be published in 2014, but Grant announced data at IAS 2013 on factors associated with participants wanting to join iPrEx-OLE and staying in it, and also on drug levels in all participants -- seen as the gold-standard way of ascertaining adherence.
In terms of recruitment, 2340 people were eligible to join iPrEx-OLE, and 1526 of these (65%) said they wished to enroll in the open-label study. Of those who did not continue, 15% dropped out while the placebo-controlled trial was still ongoing, 8% in the time gap between studies, and 12% just before iPrEx-OLE started, at the time the results of the placebo-controlled study were unblinded and individuals learned what they had taken. Another 5% became HIV positive in the gap between trials.
By far the most common reason for not continuing PrEP was concern about side effects: 49% of non-continuers cited this as a concern. Other concerns were less common: 14% said they could manage their HIV risk without PrEP, 15% said they did not like taking a pill daily, and 12% said they did not like taking the pills at all. In addition, 7% feared people would think they had HIV if they took PrEP and 3% feared it would out them as gay; 9% feared developing drug resistance. These are non-exclusive figures, as people could cite more than 1 reason.
People who elected to continue into iPrEx-OLE were older (76% of over-30s continued versus 68% of under-25s) and were less well educated. Wishing to continue was related to HIV risk: 79% and 74% of those who had anal sex with, and without, condoms versus 64% who said they did not have anal sex continued into iPrEx-OLE.
Perhaps surprisingly, 62% of the roughly 50% of placebo-controlled study participants who had undetectable drug levels wanted to continue PrEP, while 75% of those who always had detectable drug levels did so.
Drug-level monitoring was done in all participants, using a test sensitive to 1 dose of drug during the previous 3 days. To avoid the "white coat effect," where non-adherent participants take a pill immediately before their clinic visit, a drug level test was performed at either week 4, week 8, or week 12 of the study, but participants were not told in advance which it would be.
Detectable drug was found in 61% to 71% of participants. Except for 1 U.S. site, drug detection was more common among all people in iPrEx-OLE than in the original trial. But rates of drug detection were only slightly higher at the other U.S. sites and the Brazilian, Thai, and South African sites. At the sites in Peru and Ecuador, however -- where only 30% had detectable drug at some sites in the original trial -- over 61% had detectable drug at all sites, indicating a doubling of adherence.
Detectable drug was associated with older age and higher education. There was a slight tendency for participants who had condom-free sex to have less detectable drug, but this was not statistically significant.
Asked if he was disappointed that about 65% of 65% of participants in the original study -- or 42% -- both elected to continue into iPrEX-OLE and take the study drug, Grant pointed out that taking PrEP daily was not a requirement of staying in iPrEx-OLE: participants could stop and restart PrEP in consultation with researchers and if they agreed to an HIV test before resumption.
"PrEP is not for everyone, or even necessarily for a majority," Grant said. "We feel, however, that PrEP is an indication for a lot of people who for one reason or another cannot access or use condoms."
"We are also finding consistently that HIV prevention methods are synergistic and do not detract from each other: starting PrEP may well also involve testing more often, being linked to care if you do test positive, and accessing a range of support," he added.
K Choopanya, S Vanichseni, P Suntharasamai, M Martin, et al (Bangkok Tenofovir Study Group). The Bangkok Tenofovir Study, an HIV pre-exposure prophylaxis trial in Thailand: participant adherence and study results. 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention. Kuala Lumpur, June 30-July 3, 2013. Abstract WELBC05.
S Vanichseni, M Martin, P Suntharasamai, et al (Bangkok Tenofovir Study Group). HIV-associated risk behaviour among injecting drug users participating in an HIV pre-exposure prophylaxis trial in Bangkok, Thailand. 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention. Kuala Lumpur, June 30-July 3, 2013. Abstract MOLBPE27.
R Grant, V McMahan, R Amico, et al (iPrEx Study Team). Drug detection during open-label extension of the iPrEx trial indicates sustained and appropriate interest in PrEP among men who have sex with men. 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention. Kuala Lumpur, June 30-July 3, 2013. Abstract WELBC02.