Screening for HIV Infection in Asymptomatic, Nonpregnant Adolescents and Adults [Entered Retrospectively]

Project Summary Title and Description

Title
Screening for HIV Infection in Asymptomatic, Nonpregnant Adolescents and Adults [Entered Retrospectively]
Description
Background: A 2012 systematic review on HIV screening for the U.S. Preventive Services Task Force (USPSTF) found strong evidence that antiretroviral therapy (ART) is associated with improved clinical outcomes in persons with CD4+ T helper cell (CD4) counts less than 500 cells/mm3 and substantially decreases risk of HIV transmission, with certain antiretroviral agents potentially associated with long-term cardiovascular harms. The USPSTF previously found HIV screening tests to be highly accurate. Purpose: To systematically update the 2012 USPSTF review on screening for HIV in adolescents and adults, focusing on research gaps identified in the prior review. Data Sources: We searched the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and MEDLINE (2012 to June 2018) and manually reviewed reference lists, with surveillance through January 2019. Study Selection: Randomized, controlled trials (RCTs) and controlled observational studies on benefits and harms of screening versus no screening and on the yield of screening at different intervals; the effects of earlier versus later initiation of ART; and long-term (≥2 years) harms of ART. Data Extraction: One investigator abstracted data and a second investigator checked data abstraction for accuracy. Two investigators independently assessed study quality using methods developed by the USPSTF. Data Synthesis (Results): We did not identify any studies on benefits or harms of HIV screening versus no screening, or on the yield of repeat versus one-time screening or of screening at different intervals. Two new RCTs conducted completely or partially in low-resource settings found initiation of ART in persons with CD4 counts greater than 500 cells/mm3 associated with lower risk of composite clinical outcomes (mortality, AIDS-defining events, or serious non-AIDS events) (relative risk [RR], 0.44 [95% confidence interval (CI), 0.31 to 0.63] and RR, 0.57 [95% CI, 0.35 to 0.95]); early initiation of ART was not associated with increased risk of cardiovascular events. A large observational study also found initiation of ART in persons in high-resource settings with CD4 counts greater than 500 cells/mm3 to be associated with reduced risk of mortality or AIDS events, although the magnitude of effect was smaller. New evidence regarding the association between abacavir use and increased risk of cardiovascular events was inconsistent, and certain antiretroviral regimens were associated with increased risk of long-term neuropsychiatric, renal, hepatic, and bone adverse events. Limitations: Only English-language articles were included. Observational studies were included. Studies conducted in resource-poor settings were included, which might limit applicability to general screening in the United States. Conclusions: New evidence extends effectiveness of ART to asymptomatic persons with CD4 counts greater than 500 cells/mm3. Certain ART regimens may be associated with long-term cardiovascular, neuropsychiatric, hepatic, renal, or bone harms, but early initiation of ART is not associated with increased risk of cardiovascular events. Research is needed to inform optimal screening intervals.
Attribution
N/A
Authors of Report
N/A
Methodology description
Study Selection: Randomized, controlled trials (RCTs) and controlled observational studies on benefits and harms of screening versus no screening and on the yield of screening at different intervals; the effects of earlier versus later initiation of ART; and long-term (≥2 years) harms of ART. Data Extraction: One investigator abstracted data and a second investigator checked data abstraction for accuracy. Two investigators independently assessed study quality using methods developed by the USPSTF.
PROSPERO
N/A
DOI
10.26300/4h5m-t073
Notes
Data was entered retrospectively via the upload of the evidence and quality tables in Word. The files uploaded for this project include: Appendix Table 1. KQ4 Characteristics of Trials Initiating Antiretroviral Therapy for HIV at Different CD4 Counts on Clinical Outcomes Appendix Table 2. KQ4 Results of Trials Initiating Antiretroviral Therapy for HIV at Different CD4 Counts on Clinical Outcomes Appendix Table 3. KQ4 Quality Assessment of Randomized Controlled Trials Initiating Antiretroviral Therapy for HIV at Different CD4 Counts Appendix Table 4. KQ4 Characteristics of Cohort Studies Initiating Antiretroviral Therapy for HIV at Different CD4 Counts on Clinical Outcomes Appendix Table 5. KQ4 Results of Cohort Studies Initiating Antiretroviral Therapy for HIV at Different CD4 Counts on Clinical Outcomes Appendix Table 6. KQ4 Quality Assessment of Cohort Studies Initiating Antiretroviral Therapy for HIV at Different CD4 Counts Appendix Table 7. KQ5 Characteristics of Systematic Reviews of Harms of Antiretroviral Therapy for HIV Appendix Table 8. KQ5 Results of Systematic Reviews of Harms of Antiretroviral Therapy for HIV Appendix Table 9. KQ5 Quality Assessment of Systematic Reviews of Harms of Antiretroviral Therapy for HIV Appendix Table 10. KQ5 Characteristics of Studies of Harms of Antiretroviral Therapy for HIV Appendix Table 11. KQ5 Results of Studies of Harms of Antiretroviral Therapy for HIV Appendix Table 12. KQ5 Quality Assessment of Randomized Controlled Trials of Harms of Antiretroviral Therapy for HIV Appendix Table 13. KQ5 Quality Assessment of Single-Arm Cohort Studies of Harms of Antiretroviral Therapy for HIV Appendix Table 14. KQ5 Quality Assessment of Comparative Cohort Studies of Harms of Antiretroviral Therapy for HIV
Funding Source
This report is based on research conducted by the Pacific Northwest Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. HHSA-290-2015-00009-I, Task Order No. 7)

Key Questions

1. Key Question 1. What Are the Benefits of Screening for HIV Infection in Asymptomatic, Nonpregnant Adolescents and Adults on Mortality, AIDS and Opportunistic Infections, Quality of Life, Function, and Reduced Transmission of HIV and Other STIs?
2. Key Question 2. What Is the Yield of Screening for HIV Infection at Different Intervals in Asymptomatic, Nonpregnant Adolescents and Adults, and How Does the Screening Yield Vary in Different Risk Groups?
3. Key Question 3. What Are the Harms of Screening for HIV Infection in Asymptomatic, Nonpregnant Adolescents and Adults?
4. Key Question 4. What Are the Effects of Initiating ART in Adolescents and Adults With Chronic HIV Infection at a Higher Versus Lower CD4 Count on Mortality, AIDS and Opportunistic Infections, Quality of Life, Function, and Reduced Transmission of HIV and Other STIs?
5. Key Question 5. What Are the Longer-Term Harms (≥2 Years) Associated With Currently Recommended ART Regimens?

Associated Extraction Forms

Associated Studies (each link opens a new tab)

TitleAuthorsYear
Effect of Immediate Initiation of Antiretroviral Treatment in HIV-Positive Individuals Aged 50 Years or Older.2017
Effect of immediate initiation of antiretroviral therapy on risk of severe bacterial infections in HIV-positive people with CD4 cell counts of more than 500 cells per μL: secondary outcome results from a randomised controlled trial.2017
Comparative effectiveness of immediate antiretroviral therapy versus CD4-based initiation in HIV-positive individuals in high-income countries: observational cohort study.2015
Age at Entry Into Care, Timing of Antiretroviral Therapy Initiation, and 10-Year Mortality Among HIV-Seropositive Adults in the United States.2015
Initiation of antiretroviral therapy at high CD4+ cell counts is associated with positive treatment outcomes.2015
A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa.
Effects of early versus delayed initiation of antiretroviral treatment on clinical outcomes of HIV-1 infection: results from the phase 3 HPTN 052 randomised controlled trial.2014
Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection.2015
Cancer risk and use of protease inhibitor or nonnucleoside reverse transcriptase inhibitor-based combination antiretroviral therapy: the D: A: D study.2015
Cumulative and current exposure to potentially nephrotoxic antiretrovirals and development of chronic kidney disease in HIV-positive individuals with a normal baseline estimated glomerular filtration rate: a prospective international cohort study.2016
Atazanavir is not associated with an increased risk of cardio- or cerebrovascular disease events.2013
Use of antiretroviral therapy and risk of end-stage liver disease and hepatocellular carcinoma in HIV-positive persons.2016
Is there continued evidence for an association between abacavir usage and myocardial infarction risk in individuals with HIV? A cohort collaboration.2016
No Evidence of an Association Between Efavirenz Exposure and Suicidality Among HIV Patients Initiating Antiretroviral Therapy in a Retrospective Cohort Study of Real World Data.2016
Lack of association between use of efavirenz and death from suicide: evidence from the D:A:D study.2014
No association of abacavir use with myocardial infarction: findings of an FDA meta-analysis.2012
Comparative Safety and Neuropsychiatric Adverse Events Associated With Efavirenz Use in First-Line Antiretroviral Therapy: A Systematic Review and Meta-Analysis of Randomized Trials.2015
Antiretroviral drug-related liver mortality among HIV-positive persons in the absence of hepatitis B or C virus coinfection: the data collection on adverse events of anti-HIV drugs study.2013
Association between antiretroviral exposure and renal impairment among HIV-positive persons with normal baseline renal function: the D:A:D study.2013
Long-term exposure to combination antiretroviral therapy and risk of death from specific causes: no evidence for any previously unidentified increased risk due to antiretroviral therapy.2012
Durable efficacy and safety of raltegravir versus efavirenz when combined with tenofovir/emtricitabine in treatment-naive HIV-1-infected patients: final 5-year results from STARTMRK.2013
Brief Report: Randomized, Double-Blind Comparison of Tenofovir Alafenamide (TAF) vs Tenofovir Disoproxil Fumarate (TDF), Each Coformulated With Elvitegravir, Cobicistat, and Emtricitabine (E/C/F) for Initial HIV-1 Treatment: Week 144 Results.2017
Association of tenofovir exposure with kidney disease risk in HIV infection.2012
Association between tenofovir exposure and reduced kidney function in a cohort of HIV-positive patients: results from 10 years of follow-up.2013
Antiretrovirals, Fractures, and Osteonecrosis in a Large International HIV Cohort.2017
Risk of cardiovascular events associated with current exposure to HIV antiretroviral therapies in a US veteran population.2015
Real-World Assessment of Renal and Bone Safety among Patients with HIV Infection Exposed to Tenofovir Disoproxil Fumarate-Containing Single-Tablet Regimens.
Antiretroviral Therapy for the Prevention of HIV-1 Transmission.2016
Depression and Suicidal Ideation Among HIV-Infected Adults Receiving Efavirenz Versus Nevirapine in Uganda: A Prospective Cohort Study.2018

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