From an article courtesy of our friend Michael Louella at the University of Washington:
Question: Patients are asking a lot of questions about HIV prophylaxis. What is PrEP, and what do I need to know?
Response from Anne M. Teitelman, PhD, CRNP
Assistant Professor, Family and Community Health Division, School of Nursing, University of Pennsylvania; Nurse Practitioner, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania
What Is PrEP?
Pre-exposure prophylaxis (PrEP) is a promising new biomedical intervention to prevent HIV transmission in HIV-seronegative people who are at high risk of becoming exposed to HIV. PrEP involves daily oral antiretroviral medication therapy. Research is currently being conducted to assess the efficacy of 2 different combinations of antiretroviral medications: tenofovir only and a combination of tenofovir and emtricitabine (TDF/FTC) (TruvadaŽ, Gilead Sciences,
Why Do We Need PrEP?
Although an estimated 350,000 new HIV infections have been prevented in the United States between 1991 and 2006, 50,000 new cases still occur each year. According to the Centers for Disease Control and Prevention (CDC), it is estimated that 1,178,350 people were living with HIV infection in the United States in 2008 and of those, approximately 20% were undiagnosed.[2,3]
Among those living with HIV, some populations are disproportionally affected. For example, men who have sex with men (MSM) comprise 61% of new infections, and black male and female patients have an incidence rate 7 times that of white patients. Moreover, individuals in serodiscordant relationships, in which one partner is HIV-seropositive and the other partner is HIV-seronegative, are at elevated risk.
PrEP could be another key factor in comprehensive services for HIV prevention, particularly for groups at high risk of acquiring HIV. Practitioners and patients need to have the most up-to-date information to understand available options and make necessary decisions.
Current Recommendations: Who Should Get PrEP?
The US Public Health Service (USPHS) has no formal guidelines at present for the use of PrEP. However, recent research findings show promising results and the CDC has issued interim guidance. In November 2010, the National Institutes of Health (NIH) announced the results of the iPrex trial, the first large, multicountry clinical trial to provide scientific evidence that PrEP can reduce the incidence of HIV infection among MSM. This study found a 44% reduction in the incidence of HIV in MSM when TDF/FTC was taken daily and combined with other prevention methods, including HIV testing, risk-reduction counseling, condoms, and management of sexually transmitted infections (STIs). Adherence was found to be one of the greatest factors in the efficacy of TDF/FTC. In those who used TDF/FTC on 90% or more days, HIV risk was reduced by 73%, whereas those whose adherence was less than 90%, had a diminished effect on HIV risk reduction (as low as 21%).
Because the iPrEX study used an already US Food and Drug Administration-approved drug, TDF/FTC used as PrEP could have immediate implications for the
However, because of the increasing awareness and interest of high-risk populations, the CDC is leading national efforts to develop formal USPHS guidelines for the safe use of PrEP in MSM. In the meantime, the CDC has issued interim guidance for practitioners who wish to prescribe PrEP to high-risk MSM, including the following:
ˇ Confirm that the patient is at substantial and continued high risk of acquiring HIV;
ˇ Test for acute HIV infection, especially if patient is exhibiting any symptoms, because PrEP should not be started until HIV-negative serostatus is confirmed by HIV RNA testing or a repeat antibody test is performed after viral symptoms resolve;
ˇ Document negative HIV antibody test immediately preceding initiation of PrEP therapy;
ˇ Ensure proper renal function before initiation;
ˇ Screen and treat for other STIs as needed;
ˇ Provide risk-reduction and PrEP medication adherence counseling;
ˇ Prescribing guidelines include 1 tablet of TDF/FTC daily, prescribing no more than a 90-day supply, renewable only after reconfirming that the patient remains HIV-seronegative; and
ˇ Routine follow-up includes regular adherence and risk behavior assessment and counseling, HIV antibody testing, STI assessment and treatment, and additional renal function testing.
For further guidance, see the CDC Fact Sheet entitled, "Pre-exposure prophylaxis for HIV prevention: Promoting safe and effective use in the
The Mounting Evidence Supporting PrEP
Since the results from the iPrEX trial were published, further research has made progress in determining the efficacy of PrEP in populations other than MSM. In July 2011, at the 6th International AIDS Society Conference, the abstracts for both the TDF2 and Partners PrEP studies were presented. The TDF2 study compared daily TDF/FTC use with placebo in heterosexually active adults. Compared with the placebo group, TDF/FTC had an overall protective efficacy of 62.6%. In the Partners PrEP clinical trial, HIV serodiscordant couples were randomly assigned to 1 of 3 groups: tenofovir only, TDF/FTC, or a placebo group.
The participants who received tenofovir had an average of 62% fewer HIV infections, and those who received TDF/FTC had 73% fewer HIV infections than those who received a placebo. On July 10, 2011, the Data and Safety Monitoring Board recommended results of Partners PrEP be publicly reported a year and a half early and the placebo group be discontinued as a result of overwhelming evidence that PrEP reduced HIV risk in this population. The investigators will continue to compare the differences between the tenofovir-only and the TDF/FTC group, which have not been shown to be statistically significant at this time.
Not all studies have proven TDF/FTC to be efficacious. In April 2011, the FEM-PrEP trial assessing the efficacy of TDF/FTC among heterosexual women in sub-Saharan Africa was prematurely terminated at the recommendation of the Independent Data Monitoring Committee because the group of women receiving TDF/FTC had just as many new HIV infections as the placebo group. This surprising result may be attributed to a variety of biological, behavioral, or social factors still to be determined.
A dominating biological theory is that oral tenofovir may not be as effective as topical chemoprevention in maintaining vaginal concentrations of tenofovir necessary for HIV-seronegativity, as demonstrated by the CAPRISA study. The CAPRISA study found that the use of a microbicide vaginal gel containing 1% tenofovir was effective in reducing HIV acquisition by 39% when combined with risk-reduction counseling.
PrEP: Looking Ahead
The CDC, NIH, and academic institutions are currently investigating the efficacy, safety, and cost-effectiveness of PrEP in a variety of populations. The CDC is currently reviewing the evidence from the most recent clinical trials and is planning on issuing additional recommendations as more information becomes available. As PrEP studies continue to assess efficacy for a variety of at-risk groups, further research will be needed to determine best practices for effective clinical implementation.
There are also many ethical issues associated with PrEP. Given that less than one third of people infected with HIV around the world receive the antiretroviral therapy they need, determining how best to distribute already scarce resources will be important. Additionally, assessment strategies will need to be tailored for a variety of vulnerable groups within the US population to determine those most at risk of acquiring HIV.
Finally, to address the possibility of inadvertently creating resistance, clinical trials are already underway to determine the acceptability and efficacy of different intermittent PrEP strategies. As results from current and forthcoming research become available in subsequent years and the CDC makes further formal recommendations, PrEP could have the potential to significantly reduce the incidence of HIV infections in the
Dr. Teitelman acknowledges the research assistance of Amanda Webb, MSN student at the University of Pennsylvania,
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