Once again, prevention -- not treatment -- dominated an HIV conference. The latest in the string of prevention bonanzas over the past year: two separate research teams reported that the use of HIV drugs when taken by uninfected people greatly reduced the risk of getting HIV through heterosexual sex.
First, before the conference, the University of Washington released findings from its Partners PrEP ("PrEP" stands for pre-exposure prophylaxis or prevention) study conducted in Kenya and Uganda. Because its interim data clearly showed a benefit to using HIV medications to prevent transmission, the study's independent Data Safety and Monitoring Board (DSMB) recommended that the placebo (fake pill) part of the trial be stopped. Instead, the study participants who had been given a placebo would now be offered one of the two medications being studied for prevention, Viread (tenofovir) or Truvada (tenofovir combined with Emtriva). The DSMB also recommended that these results, which came years before they were expected, be made public.
In response to the early announcement from Partners PrEP, the CDC released the findings of its TDF2 study on the use of Truvada in heterosexual men and women in Botswana. TDF2 also found significant drops in the risk of HIV infection with the use of Truvada PrEP.
"These are exciting results for global HIV prevention. We now have findings from two studies showing that PrEP can work for heterosexuals, the population hardest hit by HIV worldwide," said Kevin Fenton, MD, director of the CDC's National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention.
Another prevention study presented at IAS was HPTN 052. This research showed that treatment of an HIV-positive partner in a serodiscordant couple (in which one partner has HIV and the other doesn't) not only improves that person's health, but reduces the risk of transmission by 96%.
"There are now so many potential weapons at our disposal -- to combat HIV and to prevent its transmission -- it isn't surprising there is a palpable sense of optimism and excitement here," wrote Caspar Thomson, executive director of National AIDS Map (NAM) in Great Britain, in his blog from Rome. NAM is the official online partner for scientific reporting at IAS.
All of these results came on the 2010 coattails of CAPRISA 004, a South African study which found that a gel formulation of tenofovir applied vaginally before and after sex greatly reduced the risk of becoming infected with HIV; and iPrEx, which showed that daily PrEP with Truvada reduces the risk of HIV in men who have sex with men, as well as transgender women, by 42% to 93%.
"We have witnessed two years of significant biomedical advances, the likes of which we have not seen since the antiretroviral breakthroughs of the mid-1990s," said Elly Katabira, president of the International AIDS Society, in his speech opening the conference.
"This study is the largest study to date looking at the effectiveness of PrEP," said Dr. Connie Celum, a UW professor and principal investigator of the Partners PrEP Study. The study was funded by the Bill & Melinda Gates Foundation, and the CDC co-managed two of the study's nine sites.
The study enrolled nearly 5,000 serodiscordant couples. All received safer sex counseling along with free condoms. The positive partners were not eligible for HIV treatment based on their country's criteria.
Study co-chair Jared Baeten, MD, PhD, also with UW, presented the results at IAS. There was a decreased risk of acquiring HIV of between 62% and 73%, with no statistically significant difference in whether participants used Viread or Truvada. Both medications involve taking one pill once daily.
In a conference session titled "Treatment is Prevention: The Proof is Here," Myron Cohen, MD, of the University of North Carolina at Chapel Hill, presented results of HPTN 052, opening exuberantly with, "We hope that you will be as excited as we are about the results." The audience was, and Dr. Cohen received a standing ovation when his presentation was done.
HPTN 052 (conducted by the HIV Prevention Trials Network, of the U.S.), sought to learn whether treating positive people with HIV medications would help prevent transmission to their HIV-negative partners, as had been seen in observational studies, just looking at patients' medical charts. HPTN 052 instead used the gold standard of research: a prospective, randomized, controlled clinical trial. In other words, they set out to answer the question, enrolled participants, and used a control group not given medication to see if meds really made a difference. The results were, as stated in the title of the session, proof that HIV treatment is also HIV prevention.
HPTN 052 looked at more than 1,700 serodiscordant couples around the world. There were 13 sites in nine countries. Of 28 infections that were genetically connected to the positive partner, only one transmission occurred among the 886 participants put immediately on HIV treatment, compared to 27 in the 877 who were given delayed therapy. This represented a 96% decreased risk of infection when positive people take HIV therapy.
The CDC, which has already issued interim guidelines on the use of PrEP in men who have sex with men, urged health care providers and sexually active heterosexuals to wait for guidance on the use of PrEP in the straight population. The CDC pointed out that PrEP can only be used if an individual has been confirmed to be HIV-negative, that only daily PrEP use has been shown to be effective to date, and that "PrEP should never be seen as the first line of defense against HIV. It was only shown to be effective in clinical trials when provided in combination with regular HIV testing, condoms, and other proven prevention methods."
Risk reduction of 63% overall was seen with Truvada in the TDF2 study. With a separate analysis that excluded HIV infections which occurred more than 30 days after a participant's last Truvada dose, an even higher reduction in risk of 78% was seen. More analyses on factors such as adherence and detectable levels of medicine in the blood are underway.
A group of 1,200 heterosexual men and women participated in TDF2. All of them received free male and female condoms, screening and treatment of sexually transmitted infections, and individualized counseling for adherence and HIV risk reduction.
Truvada side effects included dizziness, nausea, and vomiting, but usually went away after a month. The Viread in Truvada has been associated with the potential for kidney problems, and one participant experienced an elevated creatinine level, a sign of renal malfunction. The elevation went away with discontinuation of Truvada.
The good results from these and other prevention studies did not come without criticism and even outright condemnation. For example, critics note that a daily Truvada tablet costs more than a daily condom (or two or three condoms).
With all the struggles surrounding the new breakthroughs in prevention, the executive director of UNAIDS, Michel Sidibé, declared in his opening speech: "We have to remember that history will judge us not by our scientific breakthroughs, but how we apply them."