Final Research Plan
Human Immunodeficiency Virus (HIV): Screening
February 22, 2024
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.
Asymptomatic, Nonpregnant Adolescents and Adults
*Harms of screening include false-positive test results, anxiety and effects of labeling, and partner discord, abuse, or violence.
†Harms of treatment include adverse effects associated with antiretroviral therapy, including cardiometabolic outcomes.
Pregnant Persons
*Harms of screening include false-positive test results, anxiety and effects of labeling, and partner discord, abuse, or violence.
†Harms of treatment include adverse maternal and infant outcomes associated with use of antiretroviral therapy.
‡Outcomes other than vertical/perinatal transmission are addressed in the analytic framework on HIV screening in nonpregnant persons.
Asymptomatic, Nonpregnant Adolescents and Adults
- What are the benefits of screening for HIV in asymptomatic, nonpregnant adolescents and adults on mortality, AIDS and opportunistic infections, quality of life, function, and reduced transmission of HIV and other sexually transmitted infections?
- What is the yield (number of new diagnoses per tests performed) of repeat vs. one-time screening for HIV in asymptomatic, nonpregnant adolescents and adults, and how does the screening yield vary in different risk groups?
- What are the harms of screening for HIV in asymptomatic, nonpregnant adolescents and adults?
- What are the effects of initiating currently recommended, initial antiretroviral therapy in all adolescents and adults with chronic HIV regardless of CD4 count vs. treatment based on CD4 threshold on mortality, AIDS and opportunistic infections, quality of life, function, and reduced transmission of HIV and other sexually transmitted infections?
- What are the longer-term harms (after 2 or more years) associated with currently recommended antiretroviral therapy regimens for adolescents and adults with HIV?
Pregnant Persons
- What are the benefits of screening for HIV in pregnant persons on risk of vertical transmission of HIV?
- What are the harms of screening for HIV in pregnant persons?
- What are the harms of currently recommended antiretroviral therapy regimens for antiretroviral-naïve pregnant persons with HIV given during pregnancy?
Asymptomatic, Nonpregnant Adolescents and Adults
Contextual questions will not be systematically reviewed and are not shown in the Analytic Framework.
- What factors (e.g., race and ethnicity, age, sex, gender, sexual orientation, HIV risk category, socioeconomic status, cultural factors, educational attainment, health literacy, or geographic location) are associated with disparities in uptake of HIV screening?
- What is the effectiveness of primary care interventions to increase uptake of HIV screening in underscreened populations?
To the extent possible, we plan to describe the participant characteristics and major intervention components of the included studies. Data on population characteristics will help us explore the degree to which the findings are broadly representative of the U.S. population, including individuals across age; sex and gender; racial, ethnic, and cultural identity; socioeconomic status; and geographic region. Evidence will be evaluated to determine if there are common components of efficacious interventions, and to the extent possible, whether interventions tailored to specific groups tend to have larger effect sizes than those that are not tailored. As part of our effort to address health equity, we will search for and highlight interventions that demonstrate effectiveness in groups of individuals who historically have lower rates of screening and in traditionally stigmatized or underrepresented groups. In addition, the proposed Contextual Questions are designed to address other important health equity considerations.
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.
Asymptomatic, Nonpregnant Adolescents and Adults
| Category | Included | Excluded |
|---|---|---|
| Settings | KQs 1–3: Primary care or other settings generalizable to primary care (e.g., family planning clinics, school-based health clinics), other healthcare settings in which screening is commonly performed (e.g., sexually transmitted infection clinics, emergency room or urgent care) KQs 4, 5: Focus on studies conducted in the United States and other very high Human Development Index countries with low prevalence of HIV and in which HIV management is similar to that in the United States, unless studies are not available in those settings |
KQs 1–5: Studies conducted in non-very high Human Development Index countries, unless fair- or good-quality studies from the United States are not available |
| Populations* | KQs 1–3: Asymptomatic adolescents and adults age 13 years or older KQs 4, 5: Adolescents and adults with HIV |
KQs 1–3: Persons who have known HIV, are on dialysis, are posttransplant, have occupational exposure (due to risk of needle stick or other parenteral exposure), or have known hepatitis C virus, hepatitis B virus, or tuberculosis KQ 4: Persons who have acute HIV, are on dialysis, or are posttransplant; studies limiting enrollment to persons with hepatitis C virus, hepatitis B virus, or tuberculosis coinfection KQ 5: Same as for KQ 4, plus persons who are already or were previously taking antiretroviral therapy |
| Interventions | KQs 1–3: Rapid or standard HIV testing KQs 4, 5: Currently recommended, initial antiretroviral therapy regimens1
|
|
| Outcomes | KQs 1–4: Mortality; AIDS and opportunistic infections; quality of life; function; reduced transmission of HIV and other sexually transmitted infections KQ 2: Number of new diagnoses per screening interval KQ 3: False-positive test results, anxiety and effects of labeling, and partner discord, abuse, or violence KQ 5: Adverse outcomes associated with currently recommended antiretroviral therapy regimens, including cardiometabolic outcomes and weight gain |
|
| Comparisons | KQs 1, 3: HIV screening vs. no screening KQ 2: Repeat HIV screening vs. one-time screening KQ 4: Initiation of antiretroviral therapy regardless of CD4 count vs. initiation at a CD4 count threshold KQ 5: Currently recommended antiretroviral regimens vs. placebo, older antiretroviral therapy regimens, or one another |
|
| Study designs | KQs 1–3: Randomized, controlled trials and controlled observational studies KQ 4: Randomized, controlled trials and large (n≥1,000) controlled observational studies KQ 5: Randomized, controlled trials and large (sample size ≥1,000) controlled observational studies |
KQ 1: Uncontrolled observational studies, modeling studies |
| Timing | KQ 5: Long-term followup, defined as ≥2 years |
*For all Key Questions, subgroups of interest include those defined by sex, age (including adolescents), race or ethnicity, gender identity, and risk group.
†These regimens are recommended as initial antiretroviral treatment in certain clinical situations.
Abbreviations: 3TC = lamivudine; ABC = abacavir; ATV/c = atazanavir/cobicistat; ATV/r = atazanavir/ritonavir; BIC = bictegravir; DOR = doravirine; DRV/c = darunavir/cobicistat; DRV/r = darunavir/ritonavir; DTG = dolutegravir; EFV = efavirenz; EVG = elvitegravir; EVG/c = elvitegravir/cobicistat; FTC = emtricitabine; KQ = Key Question; RAL = raltegravir; RPV = rilpivirine; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate.
1. U.S. Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents—A Working Group of the NIH Office of AIDS Research Advisory Council. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents With HIV. Table 6. Recommended Antiretroviral Regimens for Initial Therapy. Updated March 23, 2023. Accessed February 1, 2024. https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/adult-adolescent-arv/tables-adult-adolescent-arv.pdf
Pregnant Persons
| Category | Included | Excluded |
|---|---|---|
| Settings | KQs 1, 2: Primary care or other settings generalizable to primary care (e.g., prenatal, antenatal, and family planning clinics) and other healthcare settings in which screening is commonly performed (e.g., emergency room or urgent care) KQ 3: Focus on studies conducted in the United States and other very high Human Development Index countries with low prevalence of HIV and in which management of HIV is similar to that in the United States, except for RCTs of ART and harms of treatment if currently recommended regimens or drugs are used |
KQs 1, 2: Studies of screening conducted in non-very high Human Development Index countries, unless fair- or good-quality studies in the United States are not available |
| Populations | KQs 1, 2: Asymptomatic pregnant persons not known to be HIV positive, including adolescents (ages 13 to 18 years) KQ 3: Pregnant persons who received currently recommended ART regimens while pregnant; neonates, infants, and children who were exposed to currently recommended ART regimens in utero |
KQs 1, 2: Pregnant persons who have known HIV, are on dialysis, are posttransplant, or have occupational exposure (because of risk of needle stick or other parenteral exposure); persons with known hepatitis C virus, hepatitis B virus, or tuberculosis KQ 3: Pregnant persons who are already or were previously taking ART prior to pregnancy; persons with acute HIV; studies limiting enrollment to persons with hepatitis C virus, hepatitis B virus, or tuberculosis coinfection |
| Interventions | KQs 1, 2: Rapid or standard HIV antibody testing with confirmatory testing KQ 3: Currently recommended, initial antiretroviral therapy regimens1 for antiretroviral-naïve pregnant persons with HIV, or studies that reported outcomes for combination antiretroviral regimens and reported the categorizations for ART regimens used in the study Preferred Dual-NRTI backbones:
Preferred INSTI regimens:
Preferred PI regiments:
|
KQ 3: Regimens that are clearly outside of current U.S. practice; single-drug regimens; pregnant persons who discontinued ART during pregnancy; pregnant persons with treatment interruption |
| Comparisons | KQs 1, 2: HIV screening vs. no screening KQ 3: Currently recommended antiretroviral regimens vs. placebo, older ART regimens, or one another |
|
| Outcomes | KQ 1: Vertical transmission rates* KQ 2: Harms of screening, including false-positive test results, anxiety and effects of labeling, and partner discord, abuse, or violence KQ 3: Maternal and infant harms of treatment, including long-term harms following in utero exposure to currently recommended ART regimens |
KQs 1–3: Pharmacokinetic outcomes |
| Study designs | KQs 1, 2: RCTs and controlled observational studies KQ 3: RCTs and large (n>250) observational studies that controlled for potential confounders |
KQs 1–3: Modeling studies |
| Timing | KQ 3: Any timing |
*Outcomes other than vertical/perinatal transmission are addressed in the analytic framework on HIV screening in nonpregnant persons.
Abbreviations: 3TC = lamivudine; ART = antiretroviral therapy; ABC = abacavir; DRV/r = darunavir/ritonavir; DTG = dolutegravir; FTC = emtricitabine; INSTI = integrase strand transfer inhibitor; KQ = Key Question; NRTI = nucleoside reverse transcriptase inhibitor; PI = protease inhibitor; RCT = randomized, controlled trial; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate.
- U.S. Department of Health and Human Services Panel on Treatment of HIV During Pregnancy and Prevention of Perinatal Transmission. Recommendations for the Use of Antiretroviral Drugs During Pregnancy and Interventions to Reduce Perinatal HIV Transmission in the United States. Table 6. What to Start: Initial Antiretroviral Regimens During Pregnancy for People Who Are Antiretroviral-Naive. Updated January 31, 2023. Accessed February 1, 2024. https://clinicalinfo.hiv.gov/en/guidelines/perinatal/recommendations-arv-drugs-pregnancy-what-to-start-regimens-naive?view=full
The draft Research Plan was posted on the USPSTF website for comment from November 30, 2023, to January 3, 2024. In response to comments, the USPSTF clarified that the population addressed by the evidence review on screening for HIV in nonpregnant persons is persons age 13 years or older. In addition, the USPSTF edited the analytic framework on screening for HIV in nonpregnant persons to clarify that the screening population is those who are “not known to be HIV positive.” For HIV screening in pregnant persons, the USPSTF added a footnote to clarify that outcomes other than vertical/perinatal transmission are addressed in the analytic framework on screening for HIV in nonpregnant persons.