Purpose of Review and Prior USPSTF Recommendation
The purpose of this report is to update a previous evidence review1, 2 commissioned by the U.S. Preventive Services Task Force (USPSTF) on screening for asymptomatic HIV infection in pregnant women, including adolescents. In 2005, based on the earlier review, the USPSTF recommended that clinicians screen all pregnant women for HIV (grade A recommendation).3 Although the USPSTF found no studies that directly evaluated prenatal HIV screening versus no screening on risk of mother-to-child transmission or other clinical outcomes, it found good evidence that prenatal testing is accurate and acceptable to women and that treatment with recommended interventions (combination antiretrovirals, elective Cesarean delivery in women with viral loads >1,000 copies/mL near the time of delivery, and avoidance of breastfeeding) is associated with major reductions in risk of mother-to-child transmission (from 14% to 25% in untreated women to 1% to 2% with treatment). The USPSTF concluded that benefits of treatments in reducing perinatal transmission substantially outweighed short-term harms, though evidence on long-term maternal or infant harms associated with screening and subsequent interventions was limited.1, 2 The current report will be used by the USPSTF to update its 2005 recommendation on prenatal HIV screening.
This update focuses on newer evidence on the accuracy and acceptability of rapid versus standard testing, the effectiveness of newer antiretroviral regimens for reducing mother-to-child transmission, long-term maternal outcomes following use of antiretroviral regimens during pregnancy, and maternal and infant harms associated with use of antiretroviral medications. Because perinatal practices and interventions related to prevention of HIV infection are substantially impacted by the availability of resources, the report will emphasize evidence applicable to typical practice in the United States.
HIV is a ribonucleic acid (RNA) retrovirus that infects the immune cells of its human hosts, in particular, CD4 helper T cells. HIV infection leads to acquired immune deficiency syndrome (AIDS) in most patients if left untreated. HIV is a communicable disease with two types: HIV-1 and HIV-2. HIV-2 infection is very uncommon in the United States, primarily affects persons from West Africa, and is less likely to progress to AIDS.4 AIDS is a life threatening disease defined by severe immune dysfunction (CD4 T cell count ≤0.200 × 109 cells/L) or one or more AIDS-defining opportunistic infections or neoplastic conditions.5
Prevalence and Burden of Disease
In 2009, women represented 24 percent of all diagnoses of HIV infection among adults and adolescents in the United States.6 About 300,000 U.S. women were living with HIV infection in 2008,7 with 11,200 new cases in 2009.6 The prevalence of HIV infection increases from 0.03 percent in women ages 15 to 19 years to 0.7 percent in women ages 40 to 44 years, though estimates vary depending on geographic area, demographic characteristics, and presence of risk factors.8 The prevalence of HIV infection is higher in black and Latina women compared with women of other races/ethnicities. An estimated 18 percent of women with HIV infection are unaware of their status.6, 7
Between 6,000 and 7,000 HIV-positive women give birth each year in the United States,9 with approximately 30 percent of women unaware of their HIV-positive status prior to pregnancy.10 From 2001 to 2004, approximately 7 percent of HIV-infected women in the United States were undiagnosed at the time of delivery.10 Mother-to-child transmission is responsible for more than 90 percent of pediatric HIV infections in the United States.8, 11 Through 2008, there have been nearly 5,000 cumulative deaths of individuals with perinatally acquired HIV infection, with recent estimates of 60 to 70 deaths per year.12 The number of cases of perinatal HIV infections in the United States peaked at about 1,650 in 1992, but has declined dramatically with the widespread adoption of routine prenatal screening coupled with the use of more effective therapies for preventing mother-to-child transmission, and was estimated at between 215 to 370 cases in 2005.13
Etiology and Natural History
Peripartum transmission of HIV infection can occur during pregnancy (intrauterine), during labor and delivery (intrapartum), and following delivery (postpartum). In the absence of breastfeeding, intrauterine transmission is thought to account for 25 to 40 percent of vertically infected infants, with the remainder occurring during labor and delivery.14 A high proportion of intrauterine transmission is thought to occur shortly before delivery.15 HIV is present in and transmitted through breast milk,16 and breastfeeding is thought to be the only important mode for postpartum transmission to newborns and infants.17, 18 In resource-poor settings in which women breastfeed for prolonged periods, postpartum transmission accounts for about 44 percent of infant cases.19 Antiretroviral treatment of the mother and infant does not completely eliminate breastfeeding transmission risk.20 In the United States, HIV-infected women are advised against breastfeeding, given the risk of transmission and the availability of affordable and safe alternatives.15
About 50 percent of HIV-infected pregnant women are exposed to HIV through heterosexual contact, 8 percent through injection drug use, and 8 percent through some other exposure category (such as blood transfusion or perinatal exposure).10 In about one third of women, exposure is unknown.
Well-established risk factors for perinatal transmission include high viral load, immunologically or clinically advanced disease in the mother, prolonged rupture of membranes, maternal infection with other sexually transmitted diseases, and labor and delivery procedures and events (such as abruptio placentae, fetal scalp electrode use, episiotomy, and second degree or greater perineal laceration) associated with an increased probability of bodily fluid contact between mother and infant.21
Risk factors for clinical progression of HIV infection (in particular, high viral load and low CD4 count) appear to be similar for pregnant and nonpregnant women. In developed countries, pregnancy itself does not appear to be an important independent predictor of clinical progression in chronically infected HIV-positive women.22, 23
Rationale for Screening
A major goal of prenatal screening for HIV is to reduce the risk of mother-to-child transmission through subsequent interventions. Other important goals are to improve long-term clinical outcomes in HIV-infected women, facilitate early identification of infected newborns, help women to make more informed future reproductive choices, and reduce risk of horizontal transmission through effects on risky behaviors.
The current standard of care to prevent perinatal transmission of HIV infection in the United States is a three-drug antiretroviral regimen started at the beginning of the second trimester of pregnancy or earlier (followed by treatment of the infant in the postnatal period) in all HIV-infected women (regardless of viral load or CD4 count), elective Cesarean delivery before labor or rupture of membranes in women with HIV RNA levels >1,000 copies/mL near the time of delivery, and avoidance of breastfeeding in all women.14, 24 The choice of antiretroviral drugs is based on evidence regarding effectiveness for reducing perinatal transmission, risks to the fetus, side effect profile, and other factors, such as the potential for drug interactions or the possibility of inducing antiretroviral drug resistance.
HIV-positive women identified during pregnancy may also benefit from other interventions that would be considered in nonpregnant persons with HIV infection, including long-term antiretroviral therapy, prophylaxis for opportunistic infections, immunizations, and counseling to reduce high-risk behaviors for horizontal transmission.
Current Clinical Practice
The use of repeatedly reactive enzyme immunoassay (EIA) for an office-based venipuncture specimen followed by confirmatory Western blot or immunofluorescent assay for positive tests is associated with a sensitivity and specificity >99 percent, and is the standard test for diagnosing HIV infection.25 The diagnostic accuracy of standard HIV testing is thought to be similar for pregnant and nonpregnant persons, though indeterminate results may occur slightly more frequently among parous and pregnant women.26 A revised Centers for Disease Control and Prevention (CDC) HIV testing algorithm is expected in 2012. The algorithm, which will utilize combination immunoassays that screen simultaneously for both the p24 antigen and HIV antibody and test for HIV RNA without requiring Western blot confirmation, is intended to detect acute HIV infection earlier and to differentiate HIV-2 from HIV-1 infection.27
Rapid HIV antibody tests on blood or oral fluid specimens provide results in 5 to 40 minutes compared with 1 to 2 weeks for standard testing, and are associated with diagnostic accuracy comparable with standard testing.28–30 A large, prospective cohort study of 5,744 pregnant women presenting in labor in six U.S. cities between 2001 and 2003 (HIV prevalence, 0.59%) found rapid testing (prior to confirmation) associated with a sensitivity of 100 percent, specificity of 99.9 percent, positive predictive value of 90 percent, and negative predictive value of 100 percent.28 Point-of-care rapid tests are recommended for women presenting in labor who received no prenatal care or who were not tested earlier in pregnancy for other reasons.31 Basing therapeutic decisions on a positive rapid test result prior to confirmation is only recommended in situations in which decisions to initiate treatments cannot wait, such as in women presenting in active labor. Otherwise, confirmation of positive rapid test results prior to initiating interventions is recommended due to the possibility of false-positive results,28 which could result in unnecessary exposure to antiretroviral or other therapies.
Current U.S. practice for HIV screening in pregnant women includes “opt-out” HIV screening at the initial prenatal visit as part of the standard prenatal test panel. Opt-out screening refers to screening that is performed after informing the women about the test, unless the woman specifically declines. The CDC recommends that clinicians consider repeat testing in all women in the third trimester for those who test negative initially, and recommends repeat testing for women who continue to practice high-risk behaviors or are in a high-incidence setting.31
In the United States, antiretroviral therapy is received during the prenatal and intrapartum period in about 85 percent of HIV-infected women, with about 40 percent undergoing elective Cesarean delivery.10 Over 95 percent of infants born to HIV-infected women receive antiretroviral therapy during the postnatal period.
Recommendations of Other Groups
Many groups, including the American Congress of Obstetricians and Gynecologists,14, 32 the American Academy of Family Physicians,33 the American Academy of Pediatrics,34, 35 the American College of Physicians,36 and the CDC31 recommend voluntary opt-out testing for HIV in all pregnant women as part of routine prenatal care. Although the CDC recommends that clinicians consider repeat testing for all women who are negative early in pregnancy and recommends repeat testing in women with risk factors and who are in high-incidence settings,31 the USPSTF did not address repeat testing in its 2005 recommendation.3
Agency for Healthcare Research and Quality (US), Rockville (MD)
Chou R, Cantor A, Bougatsos C, et al. Screening for HIV in Pregnant Women: Systematic Review to Update the U.S. Preventive Services Task Force Recommendation [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2012 Nov. (Evidence Syntheses, No. 96.) 1, INTRODUCTION.