This prospective, cluster randomized trial (Protocol P1031A of the International Maternal Pediatric and Adolescent AIDS Clinical Trials Group) was conducted at Macassar Midwife Obstetric Unit (MCC) and Helderberg Hospital (HH), in the Somerset West district of Western Cape Province, South Africa. It compares (1) the feasibility as well as the acceptance, by women in labor, of intrapartum and postpartum VCT for HIV infection and (2) the acceptance, by the women, of antiretroviral prophylaxis for themselves and their newborns if they test positive for HIV infection. The trial was approved by the research ethics committee of the Faculty of Health Sciences of Stellenbosch University, Stellenbosch, South Africa, and each participant provided written informed consent.
The eligibility criteria were the following: being at least 14 years old and, based on clinical estimate, at least 28 weeks pregnant; being admitted for delivery because of active labor, rupture of membranes with expected delivery, planned induction of labor, planned cesarean delivery, or obstetric/medical complications for which delivery was indicated; and being of unknown HIV status, defined as no mention of HIV status in the antenatal record for the current pregnancy and no previous record of a positive HIV test result.
The exclusion criteria were the following: taking or having taken antiretroviral drugs; progressing to the second stage of labor or having a clinical indication for immediate delivery; being in an obstetric emergency and/or medically unstable; and a fetal diagnosis of death or anomaly incompatible with life.
The eligible women were cluster randomized according to their calendar week of presentation to receive VCT either while in labor (the intrapartum arm) or following delivery but prior to hospital discharge (the postpartum arm). The randomization schedule, which was generated prior to study initiation by the method of permuted blocks, was used concurrently at both sites. The block size of 2 ensured that no more than 2 consecutive weeks were assigned to the same arm.
Trained research counselors and study nurses determined eligibility and the reasons for exclusion were recorded. Because the women were considered to be vulnerable, the study staff avoided recruitment approaches that could be perceived as coercive or misleading. The women could decline testing at any time during counseling. Selected characteristics such as age, membrane status, cervical dilation, frequency of contractions, and whether the woman had received prenatal care were extracted from the delivery log.
After counseling, each participant underwent 2 fingerstick HIV tests. These were rapid antibody assays (OraQuick [supplied by the US Centers of Disease Control] and Determine; Abbott Laboratories, Roodepoort, South Africa). A blood specimen was also taken for an enzyme-linked immunosorbent assay, performed at the PathCare Reference and Clinical Trial Laboratories, Cape Town. If both rapid test results were positive, the participant was considered HIV positive. If both rapid test results were negative, the participant was considered HIV negative. Discordant rapid tests and immunosorbent assay results were resolved by means of a Western blot.
In the intrapartum arm, women with at least 1 positive rapid test result immediately received a single, 200-mg dose of nevirapine orally and their newborns received antiretroviral prophylaxis within 72 hours of birth prior to discharge. In the postpartum arm, the newborns of women with at least 1 positive rapid test result received antiretroviral prophylaxis as soon as possible. Moreover, the newborns of women with at least 1 positive rapid test result in both arms took zidovudine twice daily for 7 days. The antiretroviral drugs were used according to the national guideline and supplied by the hospital’s pharmacy [2
]. All women received post-test counseling prior to discharge.
The women with at least 1 positive rapid test result underwent laboratory assessment and were followed up until for 6 to 12 weeks. Those with a positive result to the immunosorbent test were referred for clinical HIV care and their newborns were followed up until they were 8 to 12 weeks of age. Polymerase chain reactions (PCRs) were performed at birth and between 6 and 10 weeks of age to detect HIV-1 DNA. The infants were considered infected if the results of the first and second PCR were positive, or if the result of the PCR at birth was negative but those of the second and a third PCR, done between 8 and 12 weeks of age, were both positive. The infants were considered not to be infected if the results to the first and second PCRs were both negative, and their infection status was reported as unknown if the result to the first PCR was negative and the result of the second was missing.
Using a 2-sided χ2 test with a continuity correction and a type I error of 0.05 we determined that a sample size of 400 women would provide 80% power to detect differences between 7% and 14% in acceptance of rapid testing and between 29% and 36% in acceptance of antiretroviral prophylaxis between the 2 arms. All analyses of acceptance of testing were intent-to-treat and included all women approached for enrollment.
Groups were compared using the χ2 test or the Fisher exact test for categorical variables and the Wilcoxon rank sum test for continuous variables. Logistic regression was performed to identify prognostic factors of acceptance and adjust for potential confounding. All P values were 2-sided, with P<0.05 considered to indicate statistical significance. The software used for statistical analysis was SAS version 9.1 (SAS Institute, Cary, NC, USA) and StatXact version 1.0 (Cytel, Cambridge, MA, USA).