April 18, 2011
"Surprising and Disappointing" Results in a New Truvada PrEP Study for Women
A clinical trial testing the HIV-prevention potential of Truvada (tenofovir plus emtricitabine) in HIV-negative African women has been stopped early because of concerns about effectiveness, according to an announcement by the trial sponsor, Family Health International (FHI). This result stands in stark contrast to another study reported in late 2010, which found that Truvada cut new HIV infections by at least 44 percent in men who have sex with men (MSM) and transgender women.
Truvada is an antiretroviral (ARV) drug currently approved to treat people living with HIV. Several years ago, scientists suggested that the drug’s HIV-fighting power could also be used as prevention. Early studies in monkeys suggested that if the drug were given to HIV-negative people every day, it might keep them from becoming infected with HIV. Subsequent small studies in people found that it was likely to be safe, and so larger studies were launched in MSMs, transgender women, heterosexual women and heterosexual men.
The first of the large efficacy studies, called iPrEx, was reported in the late fall of 2010. That study—largely based in South America—found that in 2,500 MSM and transgendered women, those randomized to receive Truvada were 44 percent less likely to become infected with HIV. In those who reported taking the pill at least 90 percent of the time, new infections were cut by 73 percent, and in a small subgroup whose blood levels were monitored, Truvada appeared to cut infections by more than 90 percent in those who had measurable levels of Truvada in their blood.
The new study, FEM-PrEP, enrolled 1,951 heterosexual HIV-negative women who were at high risk for contracting HIV. The study was carried out in Kenya, Tanzania and South Africa by FHI and African academic partners. Women were randomized to receive either daily Truvada or a placebo. During a planned interim check of the data, the study monitors found that there were an equal number of new HIV infections in both the Truvada and placebo groups, making it highly unlikely that the study could determine whether or not Truvada was effective.
FHI, in its release, calls this finding “surprising and disappointing,” given the promise of Truvada in previous studies. Researchers state that follow-up with the HIV-negative study participants will be conducted over the next few months, but then an in-depth analysis of the data will occur—including Truvada blood-level monitoring data—to help understand the study’s results. Though the women in the study reported taking 95 percent of their doses, blood-level monitoring in the iPrEx revealed that fewer than 50 percent of those study participants were actually taking the drug, despite their claims otherwise.
According to FHI, “There are a number of possible reasons for the study findings, including low adherence to study regimen, a true lack of effect of the product among women (versus men who have sex with men), or other factors still to be determined.”
In fact, one especially surprising result—which also suggests poor adherence could be at least part of the explanation—is that women taking Truvada were also more likely to become pregnant, despite the use of hormonal contraceptives, than women taking a placebo. “That’s both a surprising finding and one that we can’t readily explain,” Timothy Mastro, MD, from FHI, told The New York Times.
No study conducted in the past decade has ever suggested that tenofovir could interfere with the blood levels of hormonal contraceptives. The researchers will be looking very closely to determine the reason for the additional pregnancies in the Truvada group.
It will take time to understand exactly what happened in the FEM-PrEP study. In the meantime, said Mitchell Warren, the executive director of the AIDS Vaccine Advocacy Coalition in New York City, “[FEM-PrEP] must be seen as what it is—the closure of a single trial in a field that has generated exciting results in the recent past.”
Search: PrEP, Truvada, tenofovir, emtricitabine, iPrEx, FEM-PrEP, prevention, HIV, pre-exposure prophylaxis, Family Health International, AIDS Vaccine Advocacy Coalition, men who have sex with men, MSM, transgender, heterosexual, South Africa, Tanzania, Kenya, Timothy Mastro, Mitchell Warren
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comments 1 - 11 (of 11 total)
Rodney, San Francisco, 2011-04-27 23:10:07
Gilead's first response at the announcement of PrEP's success was that it had no intention of lowering the price of Truvada, and they've already raised its price for this year. As for "Indian drugs", CIPLA is or will be limited in the number of generics it can produce. I certainly hope you don't advocate westerners violating intnernational trade laws, putting mystery pills into our bodies and taking drugs out of African's mouths so that we can have safer bareback fun.
John Eisenhans, St. Louis, 2011-04-27 11:58:58
I favor limiting patent protection for medications. Medicine should be used to heal people, not make profits. (Profits are fine, but healing comes first.) if Gilead can't/won't make Truvada affordable for all, then their patents should be voided and the drugs should be produced and distributed at cost. India licensed manufacture of generic Truvada. It costs less than $100 for a year's supply there. Private property rights, including patents, are not absolute nor paramount.
Rodney, San Francisco, CA, 2011-04-25 12:40:36
I just noticed John E is all over the internet voicing his support for PrEP, trying to compare ALL arguements against it to antisex fundamentalist propaganda. How much is Gilead paying you John E?
Rodney, San Francisco, 2011-04-23 18:00:23
Truvada as "PrEP" isn't going to benefit anyone in the long term except Gilead. Look at most risk groups, and ask yourself if they'll really benefit in real-world situations. This is classic patent law manipulation at its most obvious. If Gilead can find a new use for the drug, they can renew their patent, and with it, stave off the financial collapse analysts predict at Truvada's patent expiration. What amazes me is that Gilead accomplished this with such broad public support.
Anthony, Kampala, 2011-04-23 14:39:38
John Eisenhans,care to compare the costs of the two interventions Condoms V Truvada?We are talking about Africa here.
Given its setting,I would actually go further to say this study wasn't ethical. I don't believe in doing studies of products in populations that have no chance of affording them upon approval.We can barely get HAART for patients who actually need it to survive and have thus resorted to using conservative treatment guidelines that bar treatment until CD4s are below 200.
Mitch, Downers Grove, IL, 2011-04-22 22:43:38
Well obviously the problem is whether the women in question failed to adhere to their regime. The critical issue is whether real people, in a non-research setting, over a prolonged period of time, are actually going to do a better job without the intensive counseling and monitoring, or if the drugs will just encourage a sense of complacency about condoms amidst similar susceptability to the virus. Of f**k it, clearly you people don't care about those nuances. PREP NOW!!! Right everyone?
Johnny, , 2011-04-22 21:38:39
Actually, this article does NOT state that the reason the trial failed was non-adherence to the medication. It states that the women claimed about 95% adherence but that in the iPrEx (a completely different trial) fewer than 50% had the drug in their blood.
Yes, the author should have written the sentence better so as to make it clear he or she was talking about two different groups of people, but in any case, they won't know what caused this failure until they do a post hoc analysis.
Albert Grenier, , 2011-04-21 14:22:57
I think the author of this article missed the opportunity to reveal the underlying issue here. Even though it was remotely suggested, it is important to stress that the reason for the "failure" of the study, was not that the drugs failed, but that the test subjects failed to adhere to the regimine. That was the callousal failure here. Let's not throw the baby out with the bathwater OK?
John Eisenhans, St. Louis, 2011-04-21 10:43:13
How about "I do not see the logic in using condoms just so people can have sex. If someone has the discipline to use condoms for HIV prevention, they surely have the discipline to be abstinent"? What's the difference?
It is clear that the problem in the study was low adherence - the women in the study simply were not taking the medicine as required. Truvada's effectiveness as PreP is over 90% when people actually take it; condoms' effectiveness is over 90% when people actually use them.
Harket Evusa, Nairobi, 2011-04-20 06:11:45
I was of the feeling that the new revelations on Truvuda's efficacy could have to do with genetic polymorphism. Africans are generally fast acetylators.The study was carried out in Kenya, Tanzania and South Africa .Hence, exclusively africans. While the first of the large efficacy studies, called iPrEx, was reported in the late fall of 2010. That study—largely based in South America. Most africans cherish traditional vegetbles which can be equatted to herbal medicines - possible interactions
Anthony, Kampala, 2011-04-18 14:08:30
comments 1 - 11 (of 11 total)
I can understand the use of PEP to prevent infection but I do not see the logic in using daily pills(PREP) just so people can bareback.If someone has the discipline to take a daily pill for HIV prevention,they surely have the discipline to use a condom
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