A study on pre-exposure prophylaxis (PrEP), English PROUD study showed the highest efficacy seen so far for this method of HIV prevention, as revealed today at the Conference on Retroviruses and Opportunistic Infections (CRYO 2015) in Seattle, United States.
The effectiveness level was 86%. For each 20 infections that could have occurred in the participants, 17 were prevented by PrPE. There were three HIV infections among 276 participants randomly selected to take daily tenofovir / emtricitabine (Truvada) to prevent HIV infection, and 19 among 269 participants who were asked to wait one year before starting PrEP.
This high level of efficacy was unexpected even by the researchers themselves, not because they thought PrEP would be inefficient, but because they thought it would require much more in-depth study to prove this fact scientifically. The reason why PROUD was able to demonstrate this efficacy through a simple study, considering prevention standards, was that the incidence of HIV - the annual rate of infection - was much higher than expected, showing that there is a population of men homosexuals at an imminent risk of contracting HIV in England that could be afforded not too expensive by PrEP
The position of the PROUD as the most successful study involving tests with PrEP lasted only 15 minutes: in the following presentation, exactly the same level of efficacy was pointed out by the French study IPERGAY - Read the specific article about it.
The study PROUD
The PROUD researchers reported their methods and participants last year at the International Conference on AIDS in Melbourne. The PROUD was conducted among 545 gay men, men who have sex with other men (MSM) and transgender women attending sexual health clinics in England.
The study was designed to find out if, if participants knew they were using PrPE, they would use condoms less and consequently would be more likely to be infected with sexually transmitted diseases (STDs). He also sought to ascertain whether PrEP could be applied in a "real life" situation, as close as possible to what clinic patients had experienced.
"We found that our concern regarding the fact of PrPE be less effective in the real world was totally unfounded. In fact, what we found was just the opposite. "
Professor Sheena McCormack
Since this meant that all participants would have to know whether or not they were using PrEP, they could not use placebo. Instead, participants were randomized into two groups, so that half of them started using PrEP immediately and the other half only one year later. Participants from both groups also received support on safe sex, condoms and STD testing. The first participants started in November of 2012, and the recruitment ended in June of 2014.
The PROUD was demolished - in other words, all participants were recalled and offered PrEP - in October of 2014, when an independent Data and Safety Monitoring Committee realized that the difference in rates of HIV infection between the two groups of the study had gone through a pre-established starting point and was so great now that it would be unethical to call all participants again and offer PrEP immediately.
O recall, after all, was excellent. Even though the frequency of quarterly visits was not perfect, and notably lower in the group that started using PrEP one year later, only seven participants in the first group and twelve in the second group could not be located. Adding up to three participants who were discovered with acute HIV infection after recruitment, this means that 267 men from the first group and 256 from the second group attended at least twice and did HIV tests.
The incidence of HIV, its efficacy and drug resistance against
The PROUD, as it is now, was conceived as a pilot study, with the intention of becoming a highly effective study involving 5000 participants.
However, the incidence of HIV, which was estimated by the researchers in 2 at 3% per year, was 8,9% in the second group. The three infections found in the first group total an annual incidence of 1,5% and this difference in 7,6% rate translates as an effectiveness of 86% (90% in the confidence interval from 58 to 96%), which is quite statistically relevant (p = 0,00002).
Researchers add the so-called confidence intervals to specify the "lack of clarity" of income, in other words, how much random results that can do so (a) deviate from the actual situation. The "true" minimum rate of effectiveness provided by the study in 58% - the lowest limit of the confidence interval - was well over 50%, which could, according to the researchers' calculations, if implemented fully, bring a significant reduction in HIV infections in gay male population.
The difference is 86% in infection rates between people in both groups regardless of whether people who contracted HIV in the first group used PrEP or not. In fact, the three participants who contracted HIV in this group were probably not taking Truvada at that time. One of the participants, who had their positive test at the first clinical visit one month after starting the drug, is more likely to have been infected shortly before the start of PrEP. The other two participants did not attend medical visits early in the treatment and were diagnosed with HIV a year or more later. One of them told the clinic in which he was diagnosed that he was not using PrEP. However, it can not be proven that these participants were not infected who were taking Truvada.
Overall, there were six participants who were known or suspected to have already been infected with HIV when they started PrEP, three at the start of the study and three at the 12th month. To imitate "real life" as much as possible, participants did not have to wait for PrEP until the test results were cleared: they were leaving the clinic with Truvada the day they took the test or, in the case of second group, at a medical visit where they were tested for HIV within a year of being evaluated.
Among these six participants, three acquired resistance to emtricitabine - the so-called MUUMXV / I mutation. None of them acquired resistance to tenofovir.
Two of the three participants who could have been infected after the start of the use of PrPE acquired resistance to the drug, although one of them was the above mentioned participants who had their positive test at the first clinical visit after one month of starting the drug use .
Adherence, side effects and post-exposure prophylaxis
The level of drug adherence must have been too high to achieve efficacy in all cases, and within a set of men who claimed to have high adherence, and whose levels were measured, drugs were found in all of them. In general, sufficient numbers of pills were prescribed to cover 86% of days on which participants would use PrEP if all adherence was 100%. Five percent of participants in the first group did not even begin to use PrEP. Fifty-six percent of the participants, on the other hand, received enough pills for 100% of the days they were taking part in the study. The other 39% were given pills, but not enough to cover them every day if membership had been 100%.
Another surprising finding was that study participants were frequent users of PEP (post-exposure prophylaxis). PEP was available to all participants, even if they were scheduled for use of PrPE, because of the possibility of exposure to HIV during periods of low drug adherence. In fact, 13 (5%) of participants in the first group used the PEP, two of them twice, and 83 (31%) of the participants in the second group, with total 174 prescriptions - more than two for each.
PrEP was disrupted by 30 participants from both groups because of some medical event, however this was considered a side effect of the drug in only 13 participants. This included two cases of kidney problems, as measured by the use of creatinine, five cases of nausea or diarrhea, two cases of joint pain and two cases of headache. More than one of these participants also complained of fatigue and abdominal pain. PrEP was restarted by two of these participants.
Sexually transmitted infections and behavior change
The data starting point reported in July of last year found high levels of sexually transmitted infections (STIs) among participants. In the randomized phase, 57% of participants in the first group and 50% in the second group were diagnosed with some STIs. This difference is not statistically significant probably in any case because members of the first group had 30% more tables of quarterly STIs during the study than members of the second group (974 vs. 749). At a news conference, Sheena McCormack reported that there were four cases of hepatitis C infection during the randomized trial period.
Professor McCormack also presented preliminary data on behavior change in the study, although not all questionnaires on participant behavior issues have been processed to date.
At baseline, participants in both groups had an average of more than 10 partners who had anal sex in the three months prior to their enrollment in the study. Of these participants, they had had sex without condom use with 2 or 3 passively and with 3 actively (perhaps with the same partners) without a significant difference between the groups.
At the end of the first year, the number of partners in the last three months remained unchanged with 10 in the first group, and reduced in the second group, but without a significant difference. The number of sexual partners with whom there was no condom use remained unchanged at an average of 2-3.
There was a change in 35% of participants in the first group who had the highest number of sexual partners with whom they did not use a condom. At the beginning, 25% of participants had at least one or had no partners with whom they had not used condoms in the previous three months, while 25% had more than six. In 12th month, 25% had none or only one and 25% had more than eight. However, this is not a sudden change and not all the data has been collected, so up to that point it is not possible to say that this is an important discovery.
CCONCLUSIONS and comments about PrEP and the IPERGAY
Professor McCormack commented that when the PROUD was planned it was a time when some commentators were saying that while PrPE could be effective in a heavily monitored setting involving controlled clinical trials of placebo, it would probably not work in the real world because of the problem of accession.
"We found that our concern regarding the fact that PrEP be less effective in the real world was totally unfounded. In fact, what we found was just the opposite. "Professor Sheena McCormack
McCormack S et al. Pragmatic Open-Label Randomised Trial of preexposure Prophylaxis: Study PROUD. Conference on Retroviruses and Opportunistic Infections (CRIO) 2015, Seattle, USA,abstract 22LB, 2015.
Sheena McCormack in his presentation at CRIO 2015.
Translated to Portuguese by: Rafael Machado Guarischi English Teacher at FAETEC