A new ad campaign from the AIDS Healthcare Foundation has kicked off another round of controversy about HIV pre-exposure prophylaxis, better known as PrEP. AHF argues that the scientific evidence does not support widespread use of Truvada for prevention, while proponents say it is more effective than condoms, which most gay men do not use all the time.
AHF has taken the position that "scientific data do not support the large-scale use of Truvada as a community-wide public health intervention," according to the ad, which will run in several publications in California and Florida, including this week's Bay Area Reporter, where it appears on the back page.
"We want the public to know that the government-sanctioned widespread scale-up of PrEP appears to be a public health disaster in the making," said AHF president Michael Weinstein.
"AHF is now the direct enemy of effective HIV prevention," countered leather community leader and B.A.R. columnist Race Bannon. "The science is clear. PrEP works. The data at this point are irrefutable to anyone paying attention. Anti-PrEP folks are now the climate change deniers of HIV prevention."
The U.S. Food and Drug Administration approved Gilead Sciences' Truvada (tenofovir plus emtricitabine) for PrEP in July 2012. In May the Centers for Disease Control and Prevention recommended that people at "substantial risk" should consider PrEP to prevent HIV infection. The World Health Organization last month also recommended PrEP as an option for at-risk gay men.
Gilead itself has so far stayed out of the PrEP controversy. Spokeswoman Cara Miller declined to comment on the AHF ad.
Conflicting figures
The AHF ad features a chart showing overall efficacy in eight major studies of PrEP using Truvada or tenofovir alone in pill or gel formulations. Figures range from a high of 75 percent in the Partners PrEP study of heterosexual couples in Africa to less than 10 percent in the Fem-PrEP study of African women.
"It's not an ideological question, it's a scientific question," Weinstein told the B.A.R. "People have accused us of not being scientific, so we decided to go back to the science and present it as it is, not based on our interpretation but on the figures in the studies."
In contrast, PrEP proponents cite efficacy figures in the 90 to 100 percent range for men who have sex with men, the group most extensively studied to date.
The battle of the numbers arises from the different ways researchers can report medical study results.
In randomized, controlled clinical trials the gold standard is "intent-to-treat" results �" how well did a drug work among everyone assigned to take it, including people who may not have used it regularly or who stopped early due to side effects or for other reasons. This is usually the primary type of data reported in medical journals.
Intent-to-treat results are thought to better reflect outcomes in the real world. A drug may have strong antiviral potency, for example, but if many people find it too inconvenient or too toxic to use regularly, its real effectiveness in practice may be low.
Another method, known as "as-treated" or "per-protocol" results, considers only the subset of study participants who actually took the drug as directed. In general, as-treated results will make a treatment look better than intent-to-treat results.
iPrEx by the numbers
The community PrEP debate mainly involves conflicting figures from the iPrEx study, which enrolled nearly 2,500 HIV-negative gay and bisexual men and a small number of transgender women at 11 sites in six countries, including San Francisco and Boston in the U.S.
Participants were randomly assigned to take either Truvada or an inactive placebo once daily. The study was blinded, meaning neither the participants nor researchers knew who was taking what. Everyone also received regular HIV testing and a package of prevention services including risk-reduction counseling and free condoms. After the main study ended, participants could continue taking Truvada in the iPrEx open-label extension, or OLE.
During an average follow-up period of about a year, the risk of HIV infection was 44 percent lower overall in the Truvada group compared with the placebo group in an intent-to-treat analysis of the main iPrEx study �" the figure cited in the AHF ad.
About half of iPrEx participants reported taking Truvada as directed most of the time, and in this group the likelihood of infection dropped by 73 percent. Among people with blood drug level measurements indicating good adherence, risk reduction was 92 percent. A mathematical model later estimated that PrEP effectiveness could reach 99 percent for people who took Truvada at least four days per week.
About 1,600 participants took part in the OLE; three-quarters chose to keep taking Truvada, while the rest served as an untreated control group. OLE participants knew they were getting the active drug and were informed about the data showing that it reduced HIV risk.
In the OLE the overall risk reduction was 49 percent in the Truvada group compared with the untreated group. Among people who had blood drug levels indicating that they took Truvada at least four times per week, there were no new infections �" an efficacy of 100 percent. However, only one-third managed to reach this level of adherence. People who took Truvada two or three times per week saw a risk reduction of 84 percent, but those who took fewer than two doses had no significant protection.
"Under more or less ideal conditions, the best they could get to was 50 percent [risk reduction]," said Weinstein. "That's not a big success �" that's a big danger."
But PrEP proponents interpret the numbers more optimistically.
"We know that people who did take the drug had very high levels of protection," Jim Pickett from the AIDS Foundation of Chicago told the B.A.R. "This drug works extraordinarily well to prevent HIV if you use it."
And, added David Evans from Project Inform, "Even if it were true that PrEP was only 44 percent effective if taken daily, that would still be helpful for guys who don't use condoms. Remember that we would probably approve an HIV vaccine at that efficacy level."
Weinstein said that AHF intends to follow up with another ad looking at the effectiveness of condoms.
The level of protection in condom studies also varies widely. While effectiveness in preventing pregnancy approaches 100 percent with perfect use, real-world protection against HIV among gay men is lower. A 2013 study by CDC researchers found that men who reported using condoms all the time were about 70 percent less likely to become infected than those who said they use them sometimes or not at all.
One advantage of PrEP over condoms is that it is more forgiving of less-than-optimal adherence.
"Having used a condom yesterday provides no protection if you don't use a condom today," said iPrEx principal investigator Dr. Robert Grant from the Gladstone Institutes. But the OLE results "demonstrate that PrEP remains highly effective, even in real-world circumstances in which adherence may not be perfect."
Supporting adherence
Proponents agree that poor adherence is the Achilles' heel of PrEP, but prefer to focus on helping people take Truvada regularly.
"We agree [with AHF] that adherence is pretty critical, but disagree about what that means in terms of implementation," said Damon Jacobs, a licensed marriage and family therapist in New York City who founded the "PrEP Facts" Facebook group.
A CVS study of adherence to drugs for high blood pressure, high cholesterol, diabetes, and depression found that fewer than 50 percent of people with prescriptions took their medications consistently, Jacobs told the B.A.R . "But we don't see Michael Weinstein telling people not to take their blood pressure meds because less that half of people can adhere in the real world."
There are evidence-based practices shown to improve adherence, including cognitive-behavioral therapy and motivational interviewing, Jacobs continued. "Let's talk about the barriers and what can we do to promote adherence," he said.
"AHF's logic that PrEP is a public health failure is based on an assumption that people are not capable of taking a pill daily," added Megan Canon from the San Francisco AIDS Foundation, creator of http://www.PrEPfacts.org. "We should give people more credit for their ability to make informed choices about their own sexual health."
PrEP advocates said the drug is a good alternative.
"For those people who are especially vulnerable to HIV infection and are inconsistent condom users or never use condoms, Truvada as PrEP is a wonderful choice to consider," Pickett told the B.A.R. "Finally we have something beyond latex. Finally we have something that is in full control of the receptive partner. Finally we have something that doesn't need to be negotiated in the heat of the moment. Finally we have something that doesn't diminish sexual pleasure and intimacy."