Draft Research Plan

Prevention of Human Immunodeficiency Virus (HIV) Infection: Preexposure Prophylaxis

February 23, 2017

Recommendations made by the USPSTF are independent of the U.S. government. They should not be construed as an official position of the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.

 

Figure 1. Analytic Framework. The analytic framework depicts the relationship between the population, intervention, outcomes, and harms of pre-exposure prophylaxis for the prevention (PrEP) of HIV infection. The far left of the framework describes the target population for screening as persons without existing HIV infection. To the right of the population is an arrow corresponding to key question 2, which represents selection of candidates for PrEP. This arrow leads to both candidate for PrEP and not a candidate for PrEP populations. From the candidate for PrEP population, an arrow leads to adherence and key question 3. This step may lead to harms, which correspond with key question 5. An arrow coming out of adherence represents key question 4. It leads to the outcomes of HIV infection and quality of life. An overarching arrow symbolizing key question 1 goes directly from use of PrEP to reduce risk for HIV infection to the same outcomes. Harms include increased risky behavior that results in acquisition of other sexually transmitted diseases; adverse effects on renal function, bone, and pregnancy-related outcomes; and infection with antiretroviral drug-resistant HIV.

* Harms include increased risky behavior that results in acquisition of other sexually transmitted diseases; adverse effects on renal function, bone, and pregnancy-related outcomes; and infection with antiretroviral drug–resistant HIV. 

Abbreviations: HIV=human immunodeficiency infection; PrEP=pre-exposure prophylaxis; STD=sexually transmitted disease.

  1. What are the benefits of pre-exposure prophylaxis (PrEP) in persons without pre-existing HIV infection versus placebo or delayed PrEP for the prevention of HIV infection and associated clinical outcomes?
    1. How do benefits differ by population subgroups?
    2. How do benefits differ by dosing strategy or regimen?
  2. What is the diagnostic accuracy of methods used to identify persons who are candidates for PrEP due to increased risk of HIV acquisition?
  3. What are rates of adherence to PrEP in U.S. primary care–applicable settings?
  4. What is the association between adherence to PrEP and effectiveness for preventing HIV acquisition?
  5. What are the harms of PrEP in persons without pre-existing HIV infection versus placebo or delayed PrEP for the prevention of HIV infection?

Contextual questions will not be systematically reviewed and are not shown in the Analytic Framework.

  1. What factors are associated with increased or decreased adherence to PrEP?
  2. What is the risk of antiretroviral drug–resistant HIV infection in persons treated with PrEP, and what is the effect of PrEP-related, antiretroviral drug–resistant HIV infection on antiretroviral treatment outcomes?

The Proposed Research Approach identifies the study characteristics and criteria that the Evidence-based Practice Center will use to search for publications and to determine whether identified studies should be included or excluded from the Evidence Review. Criteria are overarching as well as specific to each of the key questions (KQs).

  Included Excluded
Population Adolescents and adults without pre-existing HIV infection who are at increased risk of HIV acquisition Adolescents and adults who are living with HIV; children
Interventions Antiretroviral therapy regimens for PrEP  
Comparisons Placebo or delayed PrEP One PrEP regimen vs. another
Outcomes Risk of HIV acquisition, quality of life, risk of other sexually transmitted diseases, renal dysfunction, adverse bone effects, pregnancy-related outcomes, and adherence All other outcomes not listed, including condom use
Setting Primary care–relevant settings, including sexually transmitted disease clinics, Ryan White clinics, and public health departments  
Study design
  • Randomized, controlled trials for effectiveness and harms
  • Controlled observational studies for harms,* if randomized, controlled trials are lacking
  • Diagnostic accuracy studies for risk assessment
Studies that do not meet inclusion criteria

* Studies must perform statistical adjustment for potential confounders to be included.