The Facts About HIV Pre-Exposure Prophylaxis (PrEP)

Pre-exposure prophylaxis (or PrEP) is an HIV prevention strategy wherein the daily use of antiretroviral drugs is known to significantly reduce a person's risk of acquiring HIV. The evidence-based approach is considered an important part of an overall HIV prevention strategy, which includes the continued consistent use of condoms and a reduction in the number of sexual partners. PrEP is not intended to be used in isolation.

Since 2010, a series of large-scale clinical trials have shown that PrEP can reduce HIV infection risk in men who have sex with men (MSM), heterosexually active adults, and injection drug users (IDUs). In response to the evidence, on-going interim guidance has been issued by the U.S. Centers for Disease Control and Protection (CDC).

Evidence in Support of PrEP

In 2010, the iPrEx Study examined the use of PrEP among 2,499 HIV-seronegative MSM. The large, multi-country trial found that the daily oral use of Truvada (tenofovir + emtricitabine) reduced HIV transmission risk by 44%. Among 51% of the trial participants with detectable levels of Truvada in the blood—meaning those who had taken their medication as directed—the risk of infection was reduced by 68%.

Following on the heels of the iPrEX Study, a number of clinical trials were designed to explore the effectiveness of PrEP in uninfected, heterosexual men and women. The first of these, the TDF2 Study in Botswana, found that the daily oral use of Truvada reduced transmission risk by 62%.

Meanwhile, the Partners PrEP Study in Kenya and Uganda explored the use of two different drug regimens (Truvada for one group and tenofovir on its own for the other) in serodiscordant, heterosexual couples in which one partner was HIV-negative and the other was HIV-positive. Overall, risk was reduced by 75% and 67%, respectively.

In June 2013, the Bangkok Tenofovir Study investigated the efficacy of PrEP on 2,413 IDUs voluntary enrolled from drug-treatment clinics in Bangkok. Results from the trial showed that a daily oral dose of Truvada reduced risk by 49% among the men and women in the study. Consistent with earlier research, participants able to maintain drug adherence were 74% less like to be infected.

Lessons Learned From Two PrEP Trials Failures

Amid the success of these studies were two highly publicized trial failures. Both were designed to explore the effectiveness of PrEP in HIV-negative women, an approach envisioned to empower socially vulnerable females.

Disappointingly, both the FEM-PrEP Study in Kenya, South Africa and Tanzania, and the VOICE Study in South Africa, Uganda and Zimbabwe were stopped when researchers found that participants on oral PrEP did not experience any protection against HIV. Interim drug monitoring tests determined that less than 40% of the women were adhering to the daily drug regimen, with even fewer (12%) maintained consistent tenofovir levels for the duration of the trial.

What both the FEM-PrEP and VOICE studies highlighted was one of the fundamental challenges of antiretroviral therapy, namely the uncompromising relationship between drug adherence and an individual's ability to achieve the desired outcome—in this case, the prevention of infection.​

In the iPrEx Study, for example, researchers found that participants with less than 50% adherence stood an 84% chance of being infected. This was in stark contrast to those who took their pills more than 90% of the time, whose risk was reduced to 32%. Investigators estimate that if the same group took every pill as indicated, risk would drop to 8% or less.

A random analysis conducted in identified a number of common experiences and/or beliefs that likely impacted adherence among study participants. Among them:

• 10% feared others would think they had HIV
• 15% were told by someone not to take the pills, most often a family member
• 16% had too many other things to worry about
• 17% felt the pill was too big
• 28% felt at low risk for HIV 
• 32% felt that daily adherence was too difficult

These issues only serve to underscore the importance of adherence counseling, as well as the regular monitoring of HIV status, pregnancy status, medication adherence, side effects, and risk behaviors for anyone placed on PrEP.

Other Concerns and Challenges

In addition to adherence barriers, some have expressed concerns about the behavioral repercussions of PrEP—specifically whether it will lead to higher levels of unprotected sex and other high-risk behaviors. Evidence largely suggests that this is not the case.

In a 24-month, randomized trial conducted in San Francisco, Boston, and Atlanta, behavioral risk among MSM were shown to either decline or remain unchanged after initiation of PrEP. Similar results were seen in a qualitative analysis of women on PrEP in Ghana.

Meanwhile, others concerns have been raised about the emergence of drug-resistant HIV due to the use of PrEP in people unknowingly infected with HIV. Early mathematical modeling suggests that, over a 10-year period in a high-prevalence setting (like sub-Saharan Africa), around 9% of newly infected people may acquire have some level of transmitted drug resistance due to PrEP. Best case/worst case scenarios range from as low as 2% to as high as 40%.

By contrast, in a developed world setting, one study (linking data from the UK Collaborative HIV Cohort with the UK Drug Resistance Database) determined that PrEP would likely have a "negligible impact" on the spread of resistant HIV among MSM, generally considered a high-risk group in many developed countries.

PrEP Recommendations

The CDC has issued interim guidance on the use of PrEP in MSM, sexually active heterosexual adults, and IDUs. Before initiation of PrEP, the doctor will first determine the eligibility of person by:

• Performing an HIV test to confirm an HIV-negative status
• Testing for infection if the person has symptoms of acute seroconversion, or has had possible HIV exposure within the preceding month (either through unprotected sex or shared needles).
• Assessing whether the person has a substantial, on-going, high risk for acquiring HIV.
• Confirming that the person has an estimated creatinine clearance greater than 60mL per minute.
• Screening for hepatitis B (HBV) and STDs.

Additionally, doctors will assess whether a woman is either pregnant or intends to get pregnant. While there have been no reports that infants exposed to Truvada have been harmed, the safety of the drug has not yet been fully assessed. That said, the CDC does not recommend PrEP for women who are breastfeeding.

Upon confirmation of eligibility, the person will be prescribed a once-daily dose of Truvada. Risk reduction counseling would then be performed (including safer sex guidance for IDUs to prevent infection through unprotected sex).

Generally speaking, the prescription would be for no longer than 90 days, renewable only after HIV testing confirms the person remains seronegative.

Additionally, a routine STD screening should be performed twice annually, as well as a pregnancy test for women. Serum creatinine and creatinine clearance should also be monitored, ideally with first follow-up and then twice annually thereafter.