Analysis Confirms Link Between PrEP Adherence and Reduced HIV Risk, Estimates Effective Dosing

Investigators with the iPrEx study, which demonstrated that pre-exposure prophylaxis (PrEP) using tenofovir/emtricitabine (Truvada) can dramatically lower the risk of HIV infection among gay and bisexual men, have now provided estimates of adherence levels need to achieve a high degree of protection. While more complete adherence is best, men may be able to reduce their HIV risk by 90% if they take Truvada 4 times weekly, or about every other day.

As previously reported, iPrEx demonstrated that tenofovir/emtricitabine reduced the rate of HIV for men who have sex with men by approximately 40% overall and by about 70% for those who reported good adherence. Protection rose to more than 90%, however, for men with measurable drug levels in their blood.

In the new substudy analysis, published in the September 12, 2012, issue of Science Translational Medicine, researchers found that men would have to take Truvada at least 4 days per week to achieve 90% or better risk reduction, while taking the drug every day was associated that nearly complete protection.

Below is an edited excerpt from a National Institute of Allergy and Infectious Disease media advisory describing the study and its findings.

NIH-Funded Analysis Estimates Effective PrEP Dosing

Findings Apply Only to Men who Have Sex with Men

September 13, 2012 -- Several large clinical trials have demonstrated that a daily oral dose of one or two antiretroviral drugs used to treat HIV infection can prevent infection in an approach known as pre-exposure prophylaxis, or PrEP. The level of protection, however, depends on taking the drugs regularly.

For instance, the landmark iPrEx study found that overall, men who have sex with men who received a daily dose of tenofovir plus emtricitabine (Truvada) had a 44 percent lower risk of HIV infection compared with those who received a daily placebo pill. But for the subset of participants who had detectable drug in their blood -- indicating that they were actually taking Truvada regularly -- the risk of HIV infection was 92 percent less than for the placebo group. 

Led by study chair Robert M. Grant, MD, of the Gladstone Institute of Virology and Immunology, the iPrEx team recently set out to estimate what drug concentration in blood cells was associated with a 90 percent reduction in HIV infection risk, and how many Truvada doses per week would achieve that concentration. The research was funded by the National Institute of Allergy and Infectious Diseases (NIAID), the National Institute of Mental Health, the National Center for Research Resources and the National Center for Advancing Translational Sciences, all part of the National Institutes of Health.

The scientists examined data from the iPrEx study to determine the concentrations of tenofovir diphosphate, the active form of tenofovir, associated with different levels of protection from HIV acquisition. They focused on tenofovir diphosphate because it is believed to be the most important component of Truvada for PrEP.

The researchers also conducted a small study to determine the blood concentrations of tenofovir diphosphate that resulted from taking a Truvada pill 2, 4 and 7 days per week. Through their analyses, the scientists found that to achieve the 90 percent risk reduction in HIV acquisition, participants needed to take Truvada at least 4 days per week (which would achieve a concentration of roughly 16 x 10^-15 moles of tenofovir diphosphate per million blood cells). The researchers also estimated that taking Truvada daily would lead to a 99 percent reduction in HIV infection risk.

The authors caution that the findings of this study, which are relevant to men who have sex with men (the iPrEx study population), may not be applicable to other populations, such as heterosexuals. This is because the minimum protective drug concentration in the blood and the number of tablets per week required to achieve that concentration in target tissues may differ depending on the route and frequency of exposure to HIV.   

9/20/12

Reference

PL Anderson, DV Glidden, A Liu, RM Grant, et al. Emtricitabine-Tenofovir Concentrations and Pre-Exposure Prophylaxis Efficacy in Men Who Have Sex with Men. Science Translational Medicine 4(151):151ra125. September 12, 2012

Other Source

National Institutes of Allergy and Infectious Diseases. NIH-Funded Analysis Estimates Effective PrEP Dosing. Media advisory. September 13, 2012.