Final Research Plan

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

July 26, 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.

The final Research Plan is used to guide a systematic review of the evidence by researchers at an Evidence-based Practice Center. The resulting Evidence Review will form the basis of the USPSTF Recommendation Statement on this topic.

The draft Research Plan was available for comment from February 23 to March 22, 2017.

Text Description is below the image.

Text Description.

The analytic framework depicts the relationship between the population, risk assessment, intervention, outcomes, and harms of pre-exposure prophylaxis (PrEP) for the prevention of HIV infection. The far left of the framework describes the target population as persons without pre-existing HIV infection. To the right of the population is an arrow corresponding to key question 2, which represents assessment of patients for use of PrEP. This arrow leads to either being a candidate for PrEP or not being a candidate for PrEP. From the candidate for PrEP population, an arrow represents the PrEP intervention, in which rates of adherence (key question 3) are examined, as well as the outcomes of HIV infection and quality of life (key question 1) and potential harms of PrEP, including other STIs, renal dysfunction, adverse effects on bone, effects on pregnancy-related outcomes, infection with antiretroviral drug–resistant HIV, gastrointestinal harms, headaches, and discontinuation due to adverse events (key question 5). A dotted line examines the association of adherence and effectiveness of PrEP (key question 4).

* Harms also include renal dysfunction, adverse effects on bone, pregnancy-related outcomes, infection with antiretroviral drug–resistant HIV, gastrointestinal harms, headaches, and discontinuation due to adverse events.

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

  1. What are the benefits of pre-exposure prophylaxis (PrEP) in persons without pre-existing HIV infection versus placebo or no PrEP (including deferred PrEP) on the prevention of HIV infection and quality of life?
    1. How do the benefits of PrEP differ by population subgroups?
    2. How do the benefits of PrEP differ by dosing strategy or regimen?
  2. What is the diagnostic accuracy of provider or patient risk assessment tools in identifying persons at increased risk of HIV acquisition who are candidates for PrEP?
  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 versus placebo or deferred PrEP when used 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 infection with antiretroviral drug–resistant HIV in persons treated with PrEP, and what is the effect of infection with PrEP-related, antiretroviral drug–resistant HIV on treatment outcomes?

The 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
Populations Adolescents and adults without pre-existing HIV infection at increased risk of HIV acquisition* Persons living with HIV; children
Interventions Daily or on-demand/intermittent oral antiretroviral therapy with tenofovir or tenofovir-emtricitabine Other PrEP regimens
Comparisons Placebo or no PrEP (including deferred PrEP) One PrEP regimen vs. another
Outcomes Risk of HIV acquisition, quality of life, risk of other sexually transmitted infections, renal dysfunction, adverse effects on bone, pregnancy-related outcomes, and adherence to PrEP regimen Outcomes not listed, including condom use
Setting All KQs: Settings in which PrEP is delivered in ways similar to primary care settings

KQs 3, 4: United States or U.S.-relevant countries
Inpatient settings
Study design Randomized, controlled trials for effectiveness and harms; controlled observational studies for harms, if randomized, controlled trials are not available; diagnostic accuracy studies for risk assessment; and large observational studies for adherence  

* Including pregnant women.
Measures of adherence include patient diaries or self-report, pill counts, adherence monitoring devices, biochemical measures (e.g., serum drug levels), and prescription fill data.
‡ Study must perform statistical adjustment for potential confounders to be included.

The draft Research Plan was posted for public comment on the USPSTF Web site from February 23, 2017, to March 22, 2017. In response to comments, the USPSTF restricted the interventions of interest to oral PrEP regimens, including daily tenofovir-emtricitabine (the only PrEP regimen currently approved by the U.S. Food and Drug Administration). The evidence review will also assess daily tenofovir without emtricitabine, since several trials have evaluated this regimen and reported benefits similar to those of daily tenofovir-emtricitabine, and alternative dosing strategies, such as on demand or intermittent (5 days per week) dosing regimens, which are actively being studied in the United States and other settings. The USPSTF clarified that the settings of interest are those in which PrEP is administered in ways similar to primary care settings, that adherence measures will focus on adherence to the PrEP regimens, and that diagnostic accuracy will focus on risk assessment tools used by patients and providers to identify persons at higher risk for HIV acquisition. The USPSTF also clarified that pregnant women are included in the evidence review. The USPSTF also added gastrointestinal harms and headaches as additional harms of PrEP.