Another weapon against HIV

There has been good news this month. The Pope changed 2000 years of Catholic doctrine by saying condom use might under certain circumstances be OK, because it preserves life rather than prevents it. The director of UNAIDS said the world has “turned the corner” and the number of people with HIV globally is falling.

But the news that excited the most debate came from the iPrEx study, which showed it may be feasible to use anti-HIV drugs to prevent HIV as well as to treat it.¹

iPrEx stands for, translated out of Spanish, the pre-exposure prophylaxis (PrEP) initiative. The study took 2500 mainly young gay men, most of them South American, who were at high risk of HIV infection, and gave half of them a two-drug HIV pill (Truvada) and half of them a placebo. The HIV infection rate in the men on Truvada was nearly halved: the drugs cut the chance of acquiring HIV by 44%.

Not bad. But the results get complicated, and because of this reactions to the study have ranged from ecstatic to sceptical.

Animal studies had suggested that PrEP could be a lot more effective than this. In fact it was, it appeared, in people who took all their pills. Based on what participants said and the number of pills dispensed, the researchers calculated Truvada stopped nearly three-quarters of infections (73% efficacy) in people who took more than nine-in-ten doses.

So far, so good: if we could improve adherence, PrEP might be very effective. That shouldn’t be too hard, they thought, because it looked like only one-in-ten doses was being forgotten.

However, the researchers had another, more objective measure of adherence. They looked at the 34 people who became infected with HIV while supposedly taking Truvada. They found very few of them showed evidence of really having taken it. Good news in a way: few who actually took the drugs got HIV.

But they had a shock when they looked at drug levels in people who had not become infected. They could only find evidence of the drugs in half of them. The tests used could detect drugs up to a month after the last dose, so this was not due to the occasional missed dose. Not only were half of the men not actually taking their pills, four out of five of those were lying about it.

Why were they not taking the drugs? One reason may be the side-effect of mild nausea some reported in the first month. Something you might live with if the pills were saving your life, but perhaps enough to put you off if you were gambling on not getting HIV anyway.

Another hint came from interviews exploring participants’ experience of the trial. Some said they’d found the badgering to take the pills became oppressive after a while. For a peaceful life, 40% said they were taking pills when they weren’t.

In some ways, this is very exciting news. It means the ‘true’ efficacy of PrEP might be double that observed, and indeed the researchers calculated that if people took all their pills all the time, Truvada could prevent 19 out of every 20 infections. Impressive: actually better than the rate achieved by people trying to use condoms every time.

In other ways, it’s not so good. If we can’t improve adherence, then PrEP becomes another frustrating, not-quite-good-enough new prevention method, like the tenofovir microbicide gel (39% efficacy in the CAPRISA trial).

PrEP will only become a real option if it’s very effective indeed. A single dose of Truvada costs $38 a day at the US list price – and even at the discounted rates offered to developing countries, one pill costs 20 to 30 times as much as a condom. It’s going to have to be pretty effective to persuade healthcare funders to pay for it.

During a conference call about the trial, Peruvian trial director Javier Lama revealed that while iPrEx was taking place, Truvada had been unavailable to people who needed it for treatment in Peru (though its two constituent drugs had been). The Global Network of People living with HIV (GNP+) pointed out that during screening for the trial, 410 men were found to have HIV, not to mention the 110 who tested positive during it. Will they get the drugs they need?   

Although welcoming the trial in general, some activists were concerned that PrEP might divert funds away from HIV treatment, and raised other issues too. What if it encouraged people to self-medicate with HIV drugs? What if it created a black market for them? Two people during the trial who, unbeknownst to anyone, were actually developing an HIV infection when they started PrEP, appear to have developed drug-resistant HIV as a result. What if PrEP sows the seeds of resistance in the population, as substandard treatment did in the 1990s?

“We, as a community of advocates, must now confront difficult questions about roll-out, cost, HIV prevention messaging and the place PrEP takes,” was the message from the Global Forum on Men Who Have Sex with Men and HIV (MSMGF). The Forum pointed out that there was no chance of PrEP working in many parts of the world if it required that men self-identify as gay where doing so risks violence or imprisonment.

Other advocates, however, welcomed PrEP as another piece of evidence to support the contention that the only way to defeat HIV is to treat it.