CDC Trials: Pre-Exposure Prophylaxis for HIV Prevention
Trial Design and Procedures
Both of CDC's current PrEP studies are randomized, double-blind, placebo-controlled trials. All participants receive risk-reduction counseling and other prevention services. Half of the participants are randomly assigned to receive one antiretroviral pill daily (either tenofovir or tenofovir plus emtricitabine, depending on the trial), and the other half are randomly assigned to take one placebo pill daily (a similar tablet without active medication). Neither researchers nor participants know an individual's group assignment. In all, the studies involve approximately 3,600 volunteers.
To make sure that participants fully understand all aspects of their participation, all volunteers are required to pass a comprehension test prior to providing written informed consent. Study participants are also free to withdraw from the trials at any time and for any reason.
To assist participants in eliminating or reducing HIV risk behaviors, extensive counseling is provided at each study visit, and more often if needed. This interactive counseling has proven effective in reducing the risk of HIV and other STDs in multiple populations, including past participants in similar HIV prevention trials. Participants are also offered free condoms and STD testing and treatment to reduce their risk for HIV infection. The health of participants is closely monitored throughout each trial, and participants are linked to any necessary medical care.
To ensure that the studies remain on a solid scientific and ethical foundation, all study procedures and plans have been reviewed and approved by scientific and ethical review committees at CDC (called institutional review boards, or IRBs), as well as IRBs established by each host country and research site prior to trial launch. Additionally, data on safety, enrollment, and efficacy are reviewed regularly by an independent data safety and monitoring board (DSMB) for each trial. The boards review emerging data to ensure that continuing the trial is safe and to determine the point at which the results are conclusive. If scientific questions arise during the course of the research, the boards meet more frequently. CDC has worked closely with community partners at each research site to ensure active community participation throughout the course of the trial.
If the efficacy trial in Thailand proves that tenofovir is effective as PrEP for injection drug users, participants in that trial and their community will be the first to benefit. All trial participants will receive tenofovir for at least one year after efficacy is proven while CDC works with the Thai Food and Drug Administration for approval of use by the Thai health care system. CDC is also prepared to provide technical assistance and support to its international partners in designing PrEP implementation plans in those countries where CDC-sponsored trials are being conducted.
Other Ongoing PrEP Trials
CDC Participation in Partners PrEP Study
The University of Washington is working with collaborators in Kenya and Uganda to conduct the Partners PrEP Study, which is examining the safety and efficacy of two different PrEP regimens -- once-daily tenofovir and once-daily tenofovir plus emtricitabine -- among heterosexual couples. CDC co-manages two trial sites in Uganda, in conjunction with The AIDS Support Organization (TASO), the largest indigenous non-governmental organization providing HIV care in Uganda.
This randomized, double-blind, placebo-controlled study operates at nine trial sites in Kenya and Uganda and will include 3,900 serodiscordant couples (couples in which one person is HIV-infected and the other is not). Stable serodiscordant couples are the largest risk group for HIV infection in Africa, and this trial will provide important data on whether PrEP could be used to prevent new HIV infections among this population. HIV-uninfected partners are assigned to one of three groups: tenofovir, tenofovir plus emtracitabine, or placebo. All participants receive ongoing risk reduction counseling and HIV testing, and their safety is monitored by the study's DSMB and local IRBs. HIV-infected members of the discordant couples receive ongoing HIV care.
The trial is the first to test the safety and efficacy of both tenofovir and tenofovir plus emtricitabine in the same population and will allow investigators to simultaneously evaluate the two drugs as candidates for use as PrEP.
Other PrEP Studies
Several other PrEP trials are being conducted by other sponsors. For detailed information on the full range of PrEP trials underway, visit www.avac.org.
PrEP Implementation Planning in the U.S.
The positive results from the iPrEx study have immediate implications for HIV prevention among gay and bisexual men the U.S., since tenofovir plus emtricitabine pills are already FDA-approved and available with a prescription for the treatment of HIV infection. As the agency responsible for protecting public health, CDC is pursuing two primary goals in the wake of the iPrEx trial findings: developing guidance on the safe and effective use of PrEP among MSM, and determining how to most effectively use PrEP in combination with other prevention strategies to reduce new infections among MSM in the U.S.
When the iPrEx results were announced, CDC immediately provided initial cautions for anyone considering using PrEP, followed by more detailed interim clinical guidance for physicians electing to provide PrEP for HIV prevention among high-risk gay and bisexual men. For details, see CDC resources (available at www.cdc.gov/hiv/prep).
The next step is developing formal U.S. Public Health Service guidelines for PrEP, which CDC will lead in collaboration with other federal health agencies. The guidelines will be based on a full review of trial data and other research, and will incorporate input from providers, HIV prevention partners, and affected communities. The guidelines will help ensure both physicians and MSM considering PrEP have accurate information to guide decisions.
In addition to developing public health guidelines, CDC will be implementing a range of activities to promote the effective and strategic use of PrEP in the U.S., such as adapting national HIV surveillance systems to help evaluate the use and impact of PrEP, developing updated risk reduction messages for MSM that address PrEP and other proven HIV prevention strategies, and examining the costs, impact, and cost-effectiveness of PrEP compared to and in combination with other interventions.
CDC has also identified other activities that could help address remaining research questions and is currently exploring all avenues to identify resources to support them. Key among these is the need for demonstration projects in clinics serving MSM to assess feasibility, acceptability, and the impact of PrEP in real-world settings.
As results from PrEP efficacy trials among injection drug users and heterosexuals become available, CDC will evaluate the study findings and determine appropriate next steps for PrEP implementation among those populations.
This article was provided by U.S. Centers for Disease Control and Prevention. Visit the CDC's website to find out more about their activities, publications and services.
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