The Basics of PrEP

HIV pre-exposure prophylaxis—better known as PrEP—means using antiretroviral drugs to prevent the virus from gaining a foothold in the body from sexual or other exposures.

PrEP is one of the most important advances in HIV science in recent years. While PrEP uptake was slow at first, an increasing number of HIV-negative people are taking advantage of this new prevention option as a growing body of research evidence and real-world experience confirms its effectiveness and puts fears to rest.

Currently the only regimen approved for PrEP is once-daily Truvada, a combination pill containing two antiretroviral drugs: tenofovir and emtricitabine.

The U.S. Food and Drug Administration (FDA) approved Truvada for PrEP in July 2012. In May 2014 the Centers for Disease Control and Prevention (CDC) released guidelines recommending that people at substantial risk for HIV infection should consider PrEP (see CDC recommendations).

According to leading PrEP researcher Robert Grant, MD, approval of Truvada for PrEP was based on nearly 20 years of data from animal studies, safety information from millions of people using the drugs for HIV treatment, and findings from two pivotal trials of PrEP’s safety and effectiveness in thousands of HIV-negative people: the international iPrEx study of men who have sex with men and the Partners PrEP study of mixed HIV status heterosexual couples in Africa.

Studies have shown that daily Truvada PrEP reduces the risk of becoming infected with HIV by around 90% among people who take it as directed. Some studies have seen no new infections among people with blood drug levels indicating optimal adherence.

But overall PrEP efficacy has varied widely in studies of different populations, mostly due to differences in how often it is used. (See “PrEP Research: Yesterday, Today, and Tomorrow,” for details about the major PrEP studies.)

Evidence for the effectiveness of Truvada PrEP is most extensive for gay and bisexual men. But other groups can also benefit from PrEP, including heterosexuals, women who have HIV-positive partners and want to get pregnant, and people who inject drugs.

Allaying PrEP concerns

Doubts about PrEP have come mainly in four areas: side effects, drug resistance, cost and access, and its effect on condom use. While some remain skeptical, most concerns have been allayed by growing evidence from research studies and real-world use.

Truvada PrEP is safe and usually well tolerated. Some people report side effects such as headaches or gastrointestinal symptoms like nausea and diarrhea, but in a number of studies these have been mostly mild and typically lessen over time as the body adjusts to the drugs. Many people on PrEP report no side effects at all.

Although Truvada was approved for PrEP in 2012, tenofovir and emtricitabine have been approved as components of treatment of HIV-positive people since 2001 and 2003, and studies have shown they can safely be used long-term. Among HIV-positive people, tenofovir can sometimes cause kidney problems and a small amount of bone loss after starting treatment.

There is less data on tenofovir for HIV-negative people. Both iPrEx and Partners PrEP showed that people on Truvada PrEP rarely develop serious kidney problems. In fact, in some cases people with mild impairment who stopped Truvada for a while were able to restart without further problems. However, some people with pre-existing kidney impairment should not use Truvada, so kidney function should be tested before starting. A recent study showed that Truvada PrEP causes only minimal bone loss that stabilizes after the first six months.

Likewise, drug resistance has not been a problem for people with good PrEP adherence. But resistance can occur if people already have HIV when they start PrEP, or if they become infected while using it, which is why HIV testing before and during PrEP is so important. Truvada alone is not enough to control an existing HIV infection—people with HIV need combination antiretroviral therapy, usually with three drugs.

Truvada PrEP can be expensive, and cost is turning out to be a barrier for some people who want it. For the most part, health insurers are covering Truvada for PrEP, and many people have manageable co-pays. But out-of-pocket costs for some has meant giving up on the chance to get PrEP.

Finally, some fear that people taking PrEP will have more risky sex—such as having more partners or not using condoms—which could lead to increased transmission of other sexually transmitted infections (STIs).

Most PrEP studies have not shown an increase in risky sexual practices after people start PrEP (known as risk compensation). In the real world, many people are interested in PrEP because they already are not using or do not want to use condoms, including men who have trouble keeping an erection with a condom, serodiscordant (mixed-status) couples who want to conceive, and anyone who desires a feeling of greater intimacy and pleasure.

The stable rate of about 50,000 new HIV infections each year indicates that many people at risk do not or cannot use condoms consistently. PrEP offers a new tool as part of a comprehensive HIV prevention and sexual health strategy. Having more choices enables people to take the steps to prevent HIV that work best for them.