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Recommendation: Human Immunodeficiency Virus (HIV) Infection: Screening [1]

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Date: 2024-09

Burden of Disease

Since the first cases of AIDS were reported in 1981, more than 700,000 persons in the United States have died of AIDS.2 The CDC estimates that 1.1 million persons in the United States are currently living with HIV infection, including an estimated 15% who are unaware of their infection.1,3,4 The annual number of new HIV diagnoses in the United States has decreased slightly in recent years, from about 41,200 new diagnoses in 2012 to 38,300 in 2017.2 Of new diagnoses of HIV infection in 2017, 81% were among males and 19% were among females.2 Groups disproportionately affected by HIV infection in the United States include men who have sex with men, black/African American populations, and Hispanic/Latino populations. For example, the estimated overall prevalence of HIV infection in the United States is 0.4%, while the estimated prevalence among men who have sex with men is 12%.3 From 2012 to 2017, HIV diagnosis rates increased in adults aged 25 to 29 years, as well as in the American Indian/Alaska Native population.2

Perinatal HIV transmission has decreased substantially since its peak in 1992.6 There were 99 diagnoses of perinatally acquired HIV infection in 2016,2 and approximately 8700 women living with HIV give birth each year.5 There are racial/ethnic disparities in rates of perinatally acquired HIV infection; rates are 5 times greater in black/African American women than in white or Hispanic/Latino women.21 Of the 99 diagnoses of perinatally acquired HIV infection reported in 2016, 65% occurred in black/African American mothers.21

Scope of Review

To update its 2013 recommendation, the USPSTF commissioned a systematic evidence review22,23 on the benefits and harms of screening for HIV infection in nonpregnant adolescents and adults, the yield of screening for HIV infection at different intervals, the effects of initiating ART at a higher (ie, >500 cells/mL3) vs lower CD4 (a type of white blood cell in the immune system) count, and the longer-term harms associated with currently recommended ART regimens. The USPSTF also commissioned a systematic evidence review24,25 on the benefits (specifically, reduced risk of mother-to-child transmission of HIV infection) and harms of screening for HIV infection in pregnant persons, the yield of repeat screening for HIV at different intervals during pregnancy, the effectiveness of currently recommended ART regimens for reducing mother-to-child transmission of HIV infection, and the harms of ART during pregnancy to the mother and infant.

Accuracy of Screening Tests

Currently recommended antigen/antibody tests for HIV are highly accurate, with reported sensitivity ranging from 99.76% to 100% and specificity ranging from 99.50% to 100%.8 Recommended rapid HIV tests have similar sensitivity and somewhat lower reported specificity ranging from 98.6% to 100%.26

Effectiveness of Early Detection and Treatment

The USPSTF found no randomized clinical trials (RCTs) or observational studies that compared clinical outcomes between adolescents and adults screened and not screened for HIV infection. The USPSTF found no studies that evaluated the yield of repeated screening for HIV compared with 1-time screening or that compared the yield of different strategies for repeat screening (eg, risk-based screening vs routine repeat testing or repeat screening at different intervals) in adolescents and adults. The USPSTF also found no studies comparing the yield of 1-time vs repeat screening or of different frequencies of screening for HIV infection in pregnancy.

The USPSTF reviewed 3 RCTs—the HIV Prevention Trials Network (HPTN 052) trial (n = 1763),27,28 the International Network for Strategic Initiatives in Global HIV Trials Strategic Timing of Antiretroviral Treatment (INSIGHT START or START) trial (n = 4685),29 and the Early Antiretroviral Treatment and/or Early Isoniazid Prophylaxis Against Tuberculosis in HIV-Infected Adults (TEMPRANO ANRS) trial (n = 2056)30—and 3 large fair-quality cohort studies, ranging in sample size from 3532 to 55,826 (total n = 63,478),31-33 that provided evidence on the benefits of early initiation of ART.

The HPTN 052 trial randomly assigned participants to initiation of ART at CD4 cell counts of 350/mL3 to 550/mL3 or delayed initiation at CD4 cell counts of 250/mL3 or less.27 At a mean follow-up of 2.1 years, initiation of ART at higher CD4 counts was associated with decreased risk of AIDS-related events (4.5% vs 7.0%; relative risk [RR], 0.65 [95% CI, 0.44-0.95]). Effects on other outcomes (including all-cause mortality; AIDS-related mortality; and a composite outcome including death, serious AIDS-related events, and serious non–AIDS-related events, such as bacterial infection or cancer) favored early initiation of ART but were not statistically significant.28 The START trial found decreased risk of a composite end point of all-cause mortality, serious AIDS-related events, and serious non–AIDS-related events,29 and the TEMPRANO ANRS trial found decreased risk of a composite end point of all-cause mortality, progression to AIDS, AIDS-defining cancer, and non–AIDS-defining invasive bacterial disease30 in participants treated with immediate ART at CD4 cell counts greater than 500/mL3, compared with delayed treatment at lower CD4 counts.

The 3 cohort studies31-33 also provide evidence of benefit to early initiation of ART. Seven-year follow-up from the HIV Cohorts Analyzed Using Structural Approaches to Longitudinal (HIV CAUSAL) Collaboration showed that ART initiation at CD4 cell counts greater than 500/mL3 was associated with decreased risk of all-cause mortality and a composite end point of progression to AIDS or death compared with initiation at CD4 cell counts less than 350/mL3.31 A second cohort study from Canada found that initiation of ART at CD4 cell counts greater than 500/mL3 was associated with lower probability of mortality and AIDS-related morbidity than initiation at CD4 cell counts less than 500/mL3 or less than 350/mL3.32 Last, a US-based cohort study found that compared with initiation of ART within 6 months of CD4 cell counts decreasing to less than 500/mL3, there were greater risks of 10-year all-cause mortality associated with ART initiation within 6 months of CD4 cell counts decreasing to less than 350/mL3 (RR, 1.08 [95% CI, 1.00-1.16]) or 200/mL3 (RR, 1.25 [95% CI, 1.08-1.44]).33

Early initiation of ART and viral suppression has also been shown to decrease risk of HIV transmission.27 Longer-term follow-up from the HPTN 052 trial showed that early ART initiation is associated with a reduction in risk of HIV transmission to uninfected partners (RR for virologically linked transmission, 0.07 [95% CI, 0.02-0.22]),34 and 3 observational studies (Partners of People on ART—A New Evaluation of the Risks [PARTNER],35 PARTNER2,36 and Opposites Attract37) found no cases of HIV transmission among serodiscordant couples when the partner living with HIV was treated with ART and had viral suppression, during 1238, 1593, and 232.2 couple-years of follow-up, respectively.

In its discussions about the age range for routine screening, the USPSTF considered the evidence on the age-stratified incidence of HIV infection and data on the prevalence of sexual activity in youth. Data from the CDC 2017 HIV Surveillance Report show a significant increase in HIV diagnoses in the United States starting at age 15 years (compared with ages 13-14 years).2 In addition, 52% of youth in grades 9 through 12 reported engaging in sexual contact in the most recent Youth Risk Behavior Surveillance survey,38 and in earlier survey data, approximately one-third of youth reported engaging in sexual intercourse before age 16 years.39 CDC surveillance data also show a significant decrease in HIV diagnoses among adults 65 years and older.2

The USPSTF found no studies that compared rates of mother-to-child transmission of HIV infection between pregnant women screened and not screened for HIV infection. The USPSTF found several cohort studies and RCTs that provided evidence on the effectiveness of ART in decreasing rates of mother-to child transmission of HIV infection in pregnant women living with HIV.24,25 The cohort studies, all conducted in North America, Europe, or Israel, reported rates of mother-to-child transmission of less than 1.0% to 2.8% among women treated with 3 antiretroviral drugs, compared with 9.1% to as much as 67% in 1 small cohort study among untreated women.24,25 The RCTs were conducted in Africa or India (ie, settings with a lower United Nations Human Development Index than the United States) and compared the effects of a heterogeneous group of prenatal, peripartum, and postpartum ART interventions of varying durations on rates of mother-to-child transmission of HIV infection. Across all studies (both the cohort studies and RCTs), later initiation of ART during pregnancy or treatment with fewer than 3 antiretroviral drugs was associated with greater risk of mother-to-child transmission of HIV infection.24,25

Potential Harms of Screening and Treatment

Longer-term use of individual antiretroviral drugs and different ART regimens may be associated with several harms. The USPSTF reviewed several studies that reported on the long-term cardiovascular, neuropsychiatric, hepatic, renal, or bone (fracture) harms associated with the use of various antiretroviral drugs and ART regimens.22,23

Two good-quality RCTs (duration, 2.8-5 years) found no differences in risk of serious cardiovascular or cerebrovascular events between different ART regimens.40,41 Findings on the cardiovascular harms of the drug abacavir are mixed. A meta-analysis of 26 trials found no association between abacavir use and risk of myocardial infarction,42 but 2 cohort studies found that abacavir was associated with increased risk (RR, 1.98 [95% CI, 1.72-2.29] and odds ratio, 1.50 [95% CI, 1.26-1.79]).43,44

The drug efavirenz has been linked to neuropsychiatric adverse events, including depression and suicidal ideation.45 A systematic review (n = 8466; mean duration, 78 weeks) reported rates of neuropsychiatric adverse events among participants taking efavirenz; 29.6% (95% CI, 21.9%-37.3%) experienced events of any grade, 6.1% (95% CI, 4.3%-7.9%) experienced severe neuropsychiatric adverse events, 3.3% (95% CI, 2.2%-4.3%) had depression, and 0.6% (95% CI, 0.2%-1.1%) had suicidal ideation.46 However, an analysis of the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study, a large (n >49,000) international study of 11 prospective cohorts from Europe, Australia, and the United States, found no association between use of efavirenz and death from suicide,47 and an analysis of a large (n = 19,983) US administrative cohort found no association between initiation of efavirenz and increased risk of suicidal ideation.48

An analysis of the D:A:D cohorts found that tenofovir disoproxil fumarate (relative rate, 1.46 [95% CI, 1.11-1.93]) and fosamprenavir (relative rate, 1.47 [95% CI, 1.01-2.15]) were associated with increased risk of end-stage liver disease or hepatocellular carcinoma, independent of viral hepatitis status, and that emtricitabine was associated with decreased risk of these outcomes (relative rate, 0.51 [95% CI, 0.32-0.83]).49 However, the absolute risk of ART-related liver deaths in the D:A:D cohorts was low (0.04 deaths per 1000 person-years).50 Another D:A:D analysis found an association between use of tenofovir disoproxil fumarate (rate ratio, 1.14 cases per year of exposure [95% CI, 1.10-1.19]) or ritonavir-boosted atazanavir (rate ratio, 1.20 cases per year of exposure [95% CI, 1.13 to 1.26]) and increased risk of chronic kidney disease.51 A second observational study also found that tenofovir disoproxil fumarate was associated with an increased risk of renal adverse events,52 and a third observational study found that tenofovir disoproxil fumarate was associated with kidney dysfunction, which was relatively mild and tended to be stable over several years.53

A cohort study found that ever use of tenofovir disoproxil fumarate was associated with increased risk of fracture compared with nonuse (adjusted incidence rate ratio, 1.40 [95% CI, 1.05-1.70]) after follow-up of more than 86 000 person-years. However, there was no difference in risk of fracture based on cumulative duration of use (adjusted incidence rate ratio per 5 years of exposure, 1.08 [95% CI, 0.94-1.25]).54

The USPSTF reviewed several studies that assessed the harms of ART during pregnancy.24,25 One fair-quality RCT and 7 cohort studies found that antenatal ART was associated with increased risk of preterm birth (before 37 weeks of gestation) compared with no treatment or zidovudine monotherapy.55-62 No clear associations were found between ART and overall birth defects, low birth weight, small size for gestational age, stillbirth, or neonatal death.24,25 There were mixed findings on cardiovascular congenital anomalies.24,25 Two studies of HIV-exposed, uninfected infants and children found that in utero exposure to ART was not associated with lower scores on Wechsler intelligence and achievement tests in children aged 7 to 13 years63 and may be associated with less neurodevelopmental impairment64 compared with no in utero exposure to ART.

Evidence on maternal harms associated with ART during pregnancy is limited. Three older studies suggest that ART (especially with a protease inhibitor) may be associated with an increased risk of gestational diabetes.65-67 One RCT found no difference in risk of anemia between combination ART (zidovudine, lamivudine, and ritonavir-boosted lopinavir) starting at 28 to 36 weeks of gestation vs zidovudine monotherapy starting at 34 to 36 weeks of gestation until onset of labor, followed by zidovudine and a single dose of nevirapine at the onset of labor.68 Another RCT found that treatment with zidovudine-based ART resulted in increased risk of maternal adverse events vs zidovudine monotherapy (21% vs 17%; P = 0.008) and increased risk of abnormalities in blood chemistry values (5.8% vs 1.3%; P < 0.001), primarily elevated alanine aminotransferase levels.55

Estimate of Magnitude of Net Benefit

The USPSTF concludes with high certainty that early detection and treatment of HIV infection would result in substantial benefits. Screening for HIV infection in all adolescents and adults aged 15 to 65 years, persons at increased risk of infection, and pregnant persons would allow for earlier and expanded detection of HIV infection, thus resulting in earlier medical and behavioral interventions and treatment.

The USPSTF found convincing evidence that early initiation of ART for HIV infection, regardless of CD4 cell count, improves clinical outcomes and reduces the risk of sexual transmission. The USPSTF found adequate evidence that the harms of early detection and treatment of HIV infection are small, and the clinical benefits of ART substantially outweigh the potential risks of treatment in persons living with HIV. The USPSTF also found convincing evidence that screening for HIV infection in pregnant women confers substantial clinical benefits for both the mother and infant, with adequate evidence that the potential harms are small.

On the basis of these findings, the USPSTF concludes with high certainty that early detection and treatment of HIV infection results in substantial net benefit.

How Does Evidence Fit With Biological Understanding?

Diagnosis and initiation of treatment of HIV infection at the earliest stage possible is associated with improved health outcomes. Screening with highly accurate tests allows for diagnosis in the relatively long preclinical phase of HIV infection. Early treatment with ART has been shown to effectively suppress viral load and decrease the risk of AIDS-related events, serious non–AIDS-related events, and death in persons living with HIV infection. Effective treatment also decreases risk of sexual transmission of HIV by suppressing viral load in infected persons. Diagnosis and effective treatment in pregnant persons living with HIV decreases the risk of mother-to-child transmission by suppressing viral load and allowing for implementation of other prevention strategies (ie, appropriate antiretroviral treatment of the newborn and counseling about avoidance of breastfeeding).

Response to Public Comment

A draft version of this recommendation was posted for public comment on the USPSTF website from November 20 through December 26, 2018. In response to public comment, the USPSTF added information and clarified language regarding assessment of risk, high-prevalence HIV settings, and persons who may be at increased risk and warrant rescreening, as well as the importance of linkage to care after an HIV diagnosis. The USPSTF also clarified that persons not at increased risk may not need rescreening. The USPSTF clarified language describing the epidemiology of HIV and provided additional details on the HPTN 052 study. The USPSTF also added information about the data it considered in its discussions about the age at which to start and end routine screening.

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[1] Url: https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/human-immunodeficiency-virus-hiv-infection-screening

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