The analytic framework in the Figure shows the target populations, interventions, and intermediate and health outcome measures we examined. The analytic framework was developed in consultation with the USPSTF and was refined after review by 7 content experts. We included all pregnant women regardless of age. Our review considered the standard screening strategy for HIV-1 infection to be an office-based venipuncture with a repeatedly reactive serum anti-HIV enzyme-linked immunosorbent assay, followed by confirmatory Western blot or immunofluorescent assay for positive test results. The other major screening method that we considered was the use of rapid testing in women with unknown HIV status who presented to labor and delivery units. We also considered data on the use of home-based collection methods and tests using noninvasive samples such as saliva or urine in pregnant women. Testing of viral load and CD4 cell counts was considered the standard work-up to determine the stage of infection in seropositive patients.
For treatment of HIV infection in pregnant women, we evaluated recommended antiretroviral prophylaxis (to prevent mother-to-child transmission) and treatment (to improve maternal outcomes), avoidance of breastfeeding, elective cesarean section in women with viral loads greater than 1000 copies/mL, immunizations, prophylaxis against opportunistic infections, counseling to reduce risky behaviors, and routine monitoring and followup. A separate review20 reports results for the latter 4 interventions. We did not include interventions not shown to be effective or not recommended in current guidelines for antiretroviral-naive pregnant women in the United States, such as hydroxyurea, HIV immune globulin, vitamin supplementation, routine resistance testing, and specific antiretroviral agents (such as efavirenz in the first trimester or the oral liquid formulation of amprenavir) or combinations (such as stavudine plus didanosine)17,19 that are no longer recommended. The major clinical outcome of interest in this review was mother-to-child transmission of HIV. We also reviewed data on the risk for clinical progression and death in HIV-positive women whose infection is diagnosed during pregnancy. Adverse outcomes of interventions in both mothers and infants were reviewed, with emphasis on severe or intolerable events. We were particularly interested in evidence on long-term maternal and child risks from antiretroviral exposure during pregnancy. Although antiretroviral exposure is associated with significant short-term side effects, many patients can be switched to effective alternative regimens, and intolerable or serious side effects are incorporated into intention-to-treat analyses of clinical outcomes.150 Intermediate outcomes were loss of detectable viremia, improvement in CD4 cell counts, and changes in risky behaviors. We also reviewed harms from screening, work-up, and treatment. Although the potential for the development of antiretroviral resistance is an important consideration in deciding which antiretroviral regimen to use during pregnancy, we primarily focused on reviewing the effects of resistance on long-term clinical outcomes.125,126,151,152
We searched the topic of HIV in the MEDLINE® and Cochrane Library databases. Most searches were done from 1983 (the year that HIV was characterized) through 30 June 2004. For antiretroviral regimens, electronic searches were performed from 1998, the year that HAART was first recommended in U.S. guidelines;153 these searches were supplemented by an electronic search for systematic reviews of antiretroviral regimens from 1983. We performed a total of 13 searches covering the areas of risk factor assessment, screening tests, work-up, and interventions. Because a preliminary search found that search strategies limited by terms for pregnancy excluded relevant studies, we performed general searches on topics of interest and performed supplemental searches specifically related to pregnancy. Appendix B presents detailed electronic search strategies and results. Periodic hand searching of relevant medical journals, reviews of reference lists, and peer review suggestions supplemented the electronic searches. Abstracts were not included in systematic searches, but major abstracts cited in reference lists or presented at recent conferences were included. We also obtained reviews, policy statements, and other papers with contextual value.
We selected papers for full review if they were about HIV infection in pregnant women, were relevant to key questions, and met inclusion criteria. For all key questions, articles were limited to those that evaluated the general population of pregnant women with HIV infection. Although the population of interest was pregnant women with unsuspected HIV infection who would be identified by screening, we included studies of pregnant women with a broad spectrum of chronic HIV disease to get a picture of the benefits and adverse effects of screening and treatment in patients with different degrees of immune deficiency. We included studies performed in the United States, Australia, Canada, and western Europe (areas in which the epidemiology and management of chronic HIV infection are similar). When important studies for a specific key question had been performed only in other countries, we also included these studies. We excluded studies of nonhuman subjects and those without original data. We considered non-English-language papers if they reported on clinical trials and if an abstract was available in English. We searched for relevant systematic reviews for all key questions. A separate report lists additional key question—specific inclusion criteria.20
We used predefined criteria from the USPSTF to assess the internal validity of included systematic reviews, trials, and observational studies, which we rated as "good," fair," or "poor." We also rated the applicability of each study to the population that would be identified by screening. The rating system was developed by the USPSTF and is described in detail elsewhere24 and summarized in Appendix C. For included trials and systematic reviews, we abstracted information about setting, patients, interventions, and outcomes. We rated the overall body of evidence for each key question using the system developed by the USPSTF.
Table 4 estimates the outcomes from screening before the third trimester in 3 hypothetical cohorts (0.15% prevalence, 0.30% prevalence, and 5% prevalence [high risk]) of 10 000 pregnant women. We did not include areas in this table in which no reliable data were available to estimate the clinical magnitude of benefit or harm, such as harms from screening (anxiety, labeling, violence, suicide, partnership dissolution) or decreased horizontal transmission from counseling. We focused on the benefits of combination antiretroviral regimens for reducing mother-to-child transmission because this intervention has the greatest impact on transmission rates and because there were insufficient or limited data on other clinical outcomes (such as long-term maternal outcomes or horizontal transmission rates) or benefits associated with other interventions (such as prophylaxis against opportunistic infections, counseling on risky behaviors, immunizations, routine monitoring and followup, or additional benefits from elective cesarean section in women receiving HAART). For harms of interventions, we focused on the rate of postpartum complications from elective cesarean section because studies have not shown clear evidence of long-term infant adverse events from antiretroviral exposure and because there are insufficient data on the risks for antiretroviral agents on long-term maternal outcomes. We calculated NNS and NNT to prevent 1 case of mother-to-child transmission and to cause 1 postpartum complication (postpartum fever, endometritis, hemorrhage, or urinary tract infection) from elective cesarean section.
To estimate the benefits of counseling and screening for HIV infection in pregnant women, we made several assumptions. We used recent estimates of rates of combination antiretroviral therapy (60% to 90%)78-82 and elective cesarean section (37% to 50%) by HIV-infected pregnant women in the United States.78,81,83 Our estimates of the effectiveness of interventions were conservative and did not include potential benefits from elective cesarean section or avoidance of breastfeeding in women receiving combination therapy.15,88 We also did not include potential benefits from screening on long-term maternal outcomes.
Calculations of NNS and NNT were based on estimates from different sources in the literature (Appendix Table). The indicated range of estimates and variation associated with estimates were incorporated in the calculations and are reflected by the ranges in the calculated NNS and NNT. We used Monte Carlo simulations to incorporate variation associated with the estimates. The sampling distributions of the estimates used in the simulations were either the underlying distribution on which the calculation of 95% CI was based or one that best approximated the point estimate and CI. For example, if the estimate was a rate or proportion, the logit of the rate or proportion was sampled assuming an approximately normal distribution and was then transformed back to its original scale. For relative risk, we assumed that the log of relative risk was approximately normally distributed. The log of the relative risk was sampled from the normal distribution and then transformed back to relative risk. In each iteration of the Monte Carlo simulation, one sample of each proportion, relative risk, or other estimate was drawn to calculate the NNSB and NNTB. The point estimates and 95% CI of NNS and NNT were based on 1 000 000 samples. A simple program using R statistical language was written to perform simulations and calculate summary statistics.154
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