Discussions around PrEP figured in a number of sessions at the 19th Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle in March 2012.
An analysis of adherence data from the results of the Pre-Exposure Prophylaxis Initiative (iPrEx) was extensively discussed.
iPrEx, is a large ongoing study that uses Truvada (tenofovir and FTC) to prevent the acquisition of HIV by HIV-negative gay men. The initial results, released in late 2010, demonstrated that the HIV infection rate in those who took PrEP was reduced by an average of 44%, compared with those given a placebo. However, the infection rate was reduced by 73% for those participants who, by self-report and pill count, took the drugs more than 90% of the time.
During the study, men were counselled in safer-sex practices and on average they reduced their sexual partners from 18 in the previous three months from the start of the study to two in the previous three months at the end.
So, data suggests that PrEP is not only effective in reducing HIV transmissions in gay men (some of whom had high-risk behaviours) but also in reducing the number of partners they have.
CROI presenters reported on a detailed analysis of drug levels in blood and immune cells from a sub-set of iPrEx participants — some of whom remained HIV negative (including some who reported instances of receptive anal intercourse) and some of whom became HIV positive. The levels suggested that a minority of men (perhaps 18%) actually took their drugs as prescribed (a daily dose throughout the week). So, adherence was far from perfect.
Taking a single dose for at least four out of seven days in the week resulted in metabolised tenofovir drug concentrations within cells sufficient to theoretically reduce the risk of HIV infection by at least 90%. The statistical analysis also indicated that perfect adherence would result in 99% reduction in risk of infection.
There are, however, limitations to this study. It found that in the three months prior to new seroconversions, drug levels were consistently low; however, it was not able to determine what drug levels were at the time of infection. Additionally, the actual doses taken by participants would have varied significantly from what they reported as an average.
It may be that adherence was good when men were having sex and not so when they weren’t.
The study did not record that level of detail.
Additionally, the actual levels of drug that are calculated as protective were based on a small study called STRAND which looked at drug levels achieved by taking tenofovir on two, four or seven days in the week over a six-week period. The research reported at CROI looked at drug levels in iPrEx and what was protective, and compared those to the levels found in the STRAND trial, and calculated that taking the drugs four days in the week would provide a high level of protection. However, this analysis does not take into account the number or types of sex practices, and whether sexual partners might have been HIV positive.
These new data confirm what is already known about tenofovir-based PrEP. Providing it achieves sufficiently high levels in blood and immune cells, it will confer significant protection, perhaps as high as 95%, for sexually active gay men.