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 level of efficacy 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 selected at random to take daily tenofovir / emtricitabine (Truvada) to prevent HIV infection, and 19 269 between participants who were asked to wait a year before starting PrEP.
This high level of effectiveness was unexpected even by the researchers themselves, not because they thought that PrEP would be inefficient, but because they thought that a much more in-depth study would be necessary to prove this fact scientifically. The reason the PROUD able to demonstrate its effectiveness through a simple study considering the standard of prevention, was that HIV incidence - the annual rate of infection - was much larger than expected, showing that there is a population of men homosexuals in an imminent risk of contracting HIV in England that could be protected from not very expensive way for 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 effectiveness was appointed by the French study IPERGAY - Read the specific article about it.
The study PROUD
The researchers reported their PROUD methods and participants last year at the International AIDS Conference in Melbourne. The PROUD was conducted between 545 gay men, men who have sex with men(MSM)and transgender women attending sexual health clinics in England.
The study was designed in order to find out whether, if the participants knew they were using the PrPE, they would use condoms less and therefore would be infected with sexually transmitted diseases (STDs). He also wished to check whether PrEP could be applied in a situation of "real life," as close as possible that patients of clinics had already gone through.
"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 if they were or not utlizando PrEP, could not used placebo. Instead, subjects were randomized in two groups, so that half of them started using PrEP immediately and the other half after only one year. Participants in both groups also received support on safe sex, condoms and STD testing. The first participants began in November 2012, and recruitment ended in June 2014.
The PROUD was desramdomisado - in other words, all the participants were called again, are offered PrEP - in October 2014 when a Data Monitoring Committee and Independent Safety realized that the difference in HIV infection rates between the two study groups had undergone a predetermined starting point and was now so great that it would be unethical to call back all participants and offer them for PrEP immediately.
TherecallAfter all, it was excellent. Even if attendance at quarterly visits has not been perfect, and notably lower in the group started using PrEP a year later, only seven participants in the first group and twelve in the second group could not be located. In addition to three participants who were discovered with acute HIV after recruitment that means 267 men in the first group and the second group 256 attended at least twice and underwent HIV testing.
The incidence of HIV, its efficacy and drug resistance against
The PROUD, the way it is now, was designed as a pilot study, with the intention of becoming a large study of effectiveness involving 5000 participants.
However, the incidence of HIV, which was estimated by the researchers in the 2 3% per year, was 8,9% in the second group. The three infections recorded in the first group have a total annual incidence of 1,5% and this 7,6% rate difference translates to an efficacy of 86% (90 58% in the confidence interval to 96%), which is quite significant statistically (p = 0,00002).
The researchers add-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 of the two groups, regardless of the fact that people who contracted HIV in the first group used PrEP or not. In fact, the three participants who contracted HIV in this group probably were not taking Truvada at that time. One of the participants, who had his positive test at the first clinic visit after a month of the beginning of the drug, is more likely to have been infected just before starting PrEP. The other two participants did not attend more to medical visits at the beginning of treatment and were diagnosed with HIV a year or more later. One said the clinic where he was diagnosed he was not using PrEP. However, it can not be proved that these participants were not infected who were taking Truvada.
In general, there were six participants which they knew or suspected that had been infected with HIV when they started PrEP, three at baseline and three 12º month. To mimic the "real life" as much as possible, the participants did not have to wait for PrEP to the results of tests to detect substances were released: they've left the clinic with Truvada in the day that made the examination or, in the case of second group medical examination in which they were HIV testing a year later they were evaluated.
Among these six participants, three acquired resistance to emtricitabine - known mutation M184V / I. None of them acquired resistance to tenofovir.
Two of the three participants who could have been infected after starting the use of PrPE acquired drug resistance, although one of them being the aforementioned participants who had his positive test at the first clinic visit after a month of the beginning of the drug .
Adherence, side effects and post-exposure prophylaxis
The level of adherence to medication must have been too high to achieve the efficacy observed in all cases, and within a set of men who said they had high adherence, and whose levels were measured, it was found drugs in all of them. In general, pills were prescribed in sufficient numbers to cover 86% of the days in which participants would make use of PrEP is the accession of all was of 100%. Five percent of the participants in the first group have not even get the use of PrEP. Fifty six percent of the participants on the other hand, given sufficient capsules to 100% of the days that they were taking part in the study. The other 39% received pills, but not enough to cover every day if the membership had been 100%.
Another surprising finding was that participants in the studies were frequent users of PEP (post-exposure prophylaxis). PEP was available for all participants, even if they were scaled to the use of PrPE, because of the possibility of exposure to HIV during periods of low medication adherence. In fact, 13 (5%) of the first group participants used the PEP, two of them twice, and 83 (31%) of participants in the second group, with a total of 174 requirements - more than two for each.
PrEP was stopped by 30 participants of both groups because of some medical event, but it was considered a side effect of the drug in only 13 participants. This included two cases of kidney disease, as measured using 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 reset is complete for two of these participants.
Sexually transmitted infections and behavior change
The starting point of the data reported in July last year found high levels of sexually transmitted infections (STIs) in the participants. In randomisation phase, 57% of the participants in the first group and 50% of the second group were diagnosed with an STI. This difference is not statistically significant probably in any case, because the members of the first group had more frames 30% of STI quarterly during the study than the second group members (974 749 v). In a press conference, Sheena McCormack reported that there were four cases of infection with hepatitis C during the randomized trial period.
Professor McCormack also presented preliminary data on behavioral changes in the study, although not all questionnaires about behavioral issues of the participants have been processed so far.
At the beginning, participants in both groups had an average of more than ten partners who were anal sex in the three months prior to their registration in the study. Of these participants, they had had sex without using condoms with 2 3 or passively and actively 3 (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 continued unchanged with 10 in the first group, and reduced in the second group, but without 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 had the highest number of sexual partners with whom did not use condoms. At first, 25% of participants had at least one or not had partners who did not use condoms during the previous three months, while 25% had more than six. In 12º month, 25% had no or only one and 25% had more than eight. However, this is not a sudden change and not all data were collected, so until then you can not say that this is an important discovery.
CCONCLUSIONS and comments about PrEP and the IPERGAY
Professor McCormack said that when PROUD was planned was a time when some commentators were saying that while PrPE could be effective in a heavily monitored scenario involving placebo controlled clinical trials, it probably would not work in the real world due to the problem 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
S McCormack et al.Pragmatic Open-Label Randomised Trial of preexposure Prophylaxis: Study PROUD.Conference on Retroviruses and Opportunistic Infections (CRYO) 2015, Seattle, USA,abstract 22LB, 2015.
Sheena McCormack in his presentation at CRIO 2015.
Translated into Portuguese by:Rafael Machado Guarischi English teacher in FAETEC