in progress

Draft Research Plan

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

November 04, 2021

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The analytic framework depicts the relationship between the population, 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 which represents assessment of patients for use of PrEP (key question 3) which leads to boxes representing a candidate for PrEP or not a candidate for PrEP. From the candidate for PrEP population box, an arrow representing the use of PrEP to reduce risk for HIV infection leads to the effects of PrEP, through a box representing adherence, on the clinical outcomes of HIV infection and quality of life (key questions 1 and 2), and the assessment of any potential harms of PrEP (key questions 4 and 5), which include other STIs, renal dysfunction, adverse effects on bone, pregnancy-related outcomes, infection with antiretroviral drug–resistant HIV, gastrointestinal harms, headaches, and discontinuation due to adverse events.

*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 vs. 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 populations of interest (e.g., defined by age, sex, gender identity, race and ethnicity, and HIV risk category)?
    2. How do the benefits of PrEP differ by dosing strategy or regimen?
  2. What are the benefits of newer PrEP regimens (oral tenofovir alafenamide-emtricitabine [TAF-FTC], injectable cabotegravir, or the dapivirine vaginal ring) vs. tenofovir disoproxil fumarate-emtricitabine (TDF-FTC)?
  3. 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?
  4. What are the harms of PrEP vs. placebo or no PrEP when used for the prevention of HIV infection?
  5. What are the harms of newer PrEP regimens (oral TAF-FTC, injectable cabotegravir, or the dapivirine vaginal ring) vs. TDF-FTC?

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

  1. What are rates of adherence to PrEP and factors associated with increased or decreased adherence in U.S. primary care settings?
  2. How does adherence to PrEP vary according to mode of administration (e.g., oral, injectable, or vaginal ring)?
  3. 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?
  4. What factors (e.g., race and ethnicity, age, sex/gender/sexual orientation, HIV risk category, socioeconomic status, cultural factors, educational attainment, or health literacy) are associated with disparities in utilization of PrEP?
  5. What is the effectiveness of primary care interventions to reduce disparities in utilization of PrEP?
  6. What is the effectiveness of PrEP delivered using telehealth vs. office-based PrEP?

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
Populations Adolescents (ages 13 to <18 years) and adults (age ≥18 years) without pre-existing HIV infection who are at increased risk of HIV acquisition*

Patient populations of interest are defined by age, sex, gender identity, race and ethnicity, and HIV risk category

Persons living with HIV, children
Interventions KQs 1, 2, 4, 5:
  • Daily oral TDF-FTC or TDF
  • Daily oral TAF-FTC
    • Alternate dosing regimens (event-driven or intermittent dosing)
  • Injectable cabotegravir
  • Dapivirine vaginal ring
KQ 3: Provider or patient risk assessment tools
Other PrEP regimens
Comparisons KQs 1, 4: Placebo or no PrEP (including deferred PrEP)

KQs 2, 5: TDF-FTC (for TAF-FTC or cabotegravir)

KQ 3: Reference standard for HIV infection
 
Outcomes

KQs 1, 2, 4, 5: Risk of HIV acquisition, quality of life, risk of other sexually transmitted infections, risk of hepatitis C virus, renal insufficiency, fracture, and pregnancy-related outcomes; for KQ 2, lipid parameters and weight gain

KQ 3: Diagnostic accuracy measures

Outcomes not listed, including condom use
Setting Settings in which PrEP is delivered in ways applicable to U.S. primary care settings Inpatient settings
Study design KQs 1, 2: Randomized, controlled trials 

KQ 3: Diagnostic accuracy studies

KQs 4, 5:  Randomized, controlled trials; controlled observational studies for harms if randomized, controlled trials are not available
 

* Including pregnant and breastfeeding persons.
Study must perform statistical adjustment for potential confounders to be included.

Abbreviations: FTC=emtricitabine; HIV=human immunodeficiency virus; KQ=key question; PrEP=pre-exposure prophylaxis; TAF=tenofovir alafenamide; TDF=tenofovir disoproxil fumarate.

Note: Studies on PrEP vary in precision when describing the distribution of gender identity and sex at birth of study populations. In the absence of specific and detailed information on gender and sex (e.g., cisgender male, transgender male), we will use gender terminology (e.g., man, woman) rather than terminology commonly used to describe biological sex at birth (e.g., male, female, intersex). We recognize that information on gender reported in studies is often inferred or assumed based on anatomy or personal presentation and may not reflect some patients’ self-identified gender. We also recognize that binary construction of gender fails to account for individuals who do not identify as men or women. We aim to accurately describe the gender composition of the studies underlying the included evidence to the extent possible, and to use gender-inclusive language where reporting clarity can be retained without gender identifiers. In this document, the terms man and woman generally refers to cisgender man and cisgender woman, although it is not always certain that other genders are excluded.