What is the basis for studying PrEP?
The science of PrEP builds on the concept that medications can be used by healthy people to prevent infection with some diseases. The strategy, which is known as prophylaxis, is used by travelers who take medications to avoid malaria, for example. We still do not know whether pre-exposure prophylaxis can help prevent HIV infection from exposure during sex or injection-drug use. This is the question that scientists are trying to answer today.
What research has been conducted thus far?
The idea of using anti-retrovirals to prevent HIV infection dates back at least a decade. The first attempts to use them in this way involved treatment of mothers and newborns to prevent mother-to-child transmission (MTCT); and post-exposure prophylaxis (PEP) in health workers, rape victims, and other individuals who might have been exposed to HIV.
Both of these uses have important differences from the way that PrEP is being studied today. There are many factors involved in MTCT including the interplay between maternal and fetal immune systems, genetics, etc., which could affect risk of HIV infection. PEP is given to people who have already been exposed to HIV. In contrast, PrEP is targeted for use before potential exposure in people who do not have HIV.
To address whether PrEP is safe and effective for use in humans, scientists have followed the traditional sequence of experiments. Data on animal safety for the drugs being used in PrEP studies already existed from the drug development process that led to licensure of the drugs for HIV treatment. Scientists have conducted additional studies in small animals and non-human primates, which test whether PrEP-style strategies provide protection against HIV-like viruses in animals. The safety of the two drugs that are being studied has been established for HIV-positive individuals, since they are licensed for use as part of ARV regimens in people who are already HIV-positive.
Information on the non-human primate studies that looked at PrEP can be found here.
All of them found some evidence of protection and provided a rationale for moving forward with PrEP studies in humans.
Which drugs are being used?
Today the two PrEP strategies under study are (1) a single drug called tenofovir disoproxil fumarate (TDF) and (2) a combination drug called Truvada ®, which combines TDF with the drug emtricitabine.
Scientists have focused on these drugs because they have proven safe for use in humans for HIV treatment, remain in the blood stream for long periods of time, require once-daily dosing, and have unique resistance profiles—meaning that if someone developed drug resistance to TDF or Truvada, he or she would still be able to use many other types of ARVs.
Why is a single drug being tested as well as a combination?
Current PrEP studies are testing both Truvada and TDF. Both the single- and double-drug strategies have shown efficacy in animal studies. These studies were too small to provide a clear argument for testing one strategy and not the other. There could be differences in safety and/or efficacy between the two drugs, and the ongoing trials will provide more insight into these issues.
What do we know so far?
To date, data from one completed PrEP study have been presented. These data include analysis of women participants at risk of infection from heterosexual sex. These women were enrolled at three different sites in Africa: Cameroon, Ghana, and Nigeria. The trials in Cameroon and Nigeria were stopped early. Only the trial in Ghana ran to completion. Based on the data that were collected, scientists could not assess whether PrEP (in this study, a once-daily dose of TDF) helped reduce the risk of HIV infection. Among the women studied there were no serious adverse events or side effects associated with use of TDF. These links provide detailed information on the data from this trial:
- Tenofovir Disoproxil Fumarate for Prevention of HIV Infection in Women: A Phase 2, Double-Blind, Randomized, Placebo-Controlled Trial, PLoS Clinical Trials, 25 May 2007
- Abstract from XVI International AIDS Conference
- Press conference with Family Health International's Leigh Peterson who discussed data from FHI's PrEP trial
Ongoing studies will provide additional information. Details of and timeframes for these studies are can be found on the Clinical Trials page.
For additional reading on the science of PrEP, check out the list of resources (left-hand column) .
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