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Background: Prevention of mother-to-child transmission of HIV (PMTCT) programs can greatly reduce the vertical transmission rate (VTR) of HIV, and Malawi is expanding PMTCT access by offering HIV-infected pregnant women life-long antiretroviral therapy (Option B+). There is currently no empirical data on the effectiveness of Malawian PMTCT programs. This study describes a surveillance approach to obtain population-based estimates of the VTR of infants <3 months of age in Malawi immediately after the adoption of Option B+. Methods and Findings: A sample of caregivers and infants <3 months from 53 randomly chosen immunization clinics in 4 districts were enrolled. Infant dried blood spot (DBS) samples were tested for HIV exposure with an antibody test to determine maternal seropositivity. Positive samples were further tested using DNA PCR to determine infant infection status and VTR. Caregivers were surveyed about maternal receipt of PMTCT services. Of the 5,068 DBS samples, 764 were ELISA positive indicating 15.1% (14.1-16.1%) of mothers were HIV-infected and passed antibodies to their infant. Sixty-five of the ELISA-positive samples tested positive by DNA PCR, indicating a vertical transmission rate of 8.5% (6.6-10.7%). Survey data indicates 64.8% of HIV-infected mothers and 46.9% of HIV-exposed infants received some form of antiretroviral prophylaxis. Results do not include the entire breastfeeding period which extends to almost 2 years in Malawi. Conclusions: The observed VTR was lower than expected given earlier modeled estimates, suggesting that Malawi's PMTCT program has been successful at averting perinatal HIV transmission. Challenges to full implementation of PMTCT remain, particularly around low reported antiretroviral prophylaxis. This approach is a useful surveillance tool to assess changes in PMTCT effectiveness as Option B+ is scaled-up, and can be expanded to track programming effectiveness for young infants over time in Malawi and elsewhere. © 2014 Sinunu et al.
The study was reviewed and approved by the Malawi National Health Sciences Research Committee and the Boston University Medical Center Institutional Review Board (IRB). Written informed consent was obtained from all participants; caregivers provided written consent for both their and the infant’s participation. The informed consent form was approved by both reviewing IRBs. Between September and November 2011 we evaluated the national PMTCT program in four Malawi districts, adapting a surveillance approach based in under-5 clinics developed in South Africa [9], [10]. We tested dried blood spot (DBS) samples from infants <3 months of age presenting for their first immunization visit for maternal HIV antibodies and subsequently for HIV with DNA polymerase chain reaction (PCR) to calculate a population-based HIV VTR. As almost all HIV exposed infants will test positive for maternal HIV antibodies below 3 months of age even if uninfected, the VTR can be estimated as the fraction of antibody positive infants with a reactive DNA PCR (indicating HIV infection). Caregiver-infant pairs were sampled through a three-stage cluster design. The first stage purposively sampled four of the 28 Malawi districts to reflect regional diversity. Districts were sampled proportionate to HIV prevalence, and as HIV prevalence is twice as high in the Southern region (17.6% compared to 8.2% and 9.0% in the North and Central regions respectively [11]), twice as many districts were chosen in that region. Sampled districts were Nkhata Bay in the Northern region, Salima in the Central region, and Mulanje and Zomba in the Southern region (Figure 1). The second stage randomly sampled 53 health facilities within the four districts. The health facilities were sampled proportionate to district population size and stratified by urban and rural location. In the third stage, all infant-caregiver pairs meeting the inclusion criteria at the selected facilities between September and November 2011 were invited to participate. Infants were required to be less than 3 months of age to ensure detection of maternal antibodies, if present, as a marker of maternal HIV-infected status and neonatal HIV-exposure. In addition, the infant must have presented to the clinic for her or his first immunization (a pentavalent diphtheria, tetanus, pertussis, Haemophilus influenza b, and hepatitis B vaccine) scheduled for 6 weeks of age. The study approach depends on high-levels of participation in the immunization program to ensure a reasonable approximation of the total population of mother-infant pairs in Malawi. The Malawi infant immunization program reports first immunization rates surpassing 97% [11]. In addition, we required the caregiver be in a position to provide consent for biological data to be collected from the infant. Appropriate caregiver roles include parent or legal guardian. Infants were excluded if the caregiver was younger than 18 years of age. Based on an estimated 2010 HIV prevalence rate of 11% for women aged 15–49 [12], an estimated transmission rate of 13.8% [13] and an alpha-level of 5%, our sample size target was approximately 5,500 caregiver-infant pairs to obtain a sample of 600 HIV-exposed infants. Existing clinic staff were trained to collect study data. After obtaining informed consent, DBS samples were collected via heel stick from infants, and caregivers were surveyed about receipt of maternal HIV testing and PMTCT services. Additional data were collected to determine the feasibility of this surveillance approach, including detailed implementation information from data collectors during supervision visits. Study staff conducted supervision visits to all participating health facilities every two weeks to pick up collected data, conduct quality control activities, and provide additional training as needed. DBS samples were sent to the Ministry of Health National HIV Reference Laboratory in Lilongwe and tested for maternal HIV antibodies using an enzyme-linked immunosorbent assay (ELISA) test (Vironostika HIV Uni-Form II Ag/Ab BioMerieux, The Netherlands). If positive (indicating maternal HIV infection), the sample was transferred to the University of North Carolina (UNC) laboratory in Lilongwe to be tested for HIV-1 DNA using a PCR test (Amplicor HIV-1 DNA PCR V1.5 Roche) to determine the infant’s HIV status. Individual test results were returned to clinics to be provided to infant caregivers at the subsequent infant immunization visit. We calculated population and district level VTR estimates and conducted analyses describing characteristics of PMTCT participation for mothers with ELISA positive infants. Estimates were calculated using Generalized Estimating Equations to account for the clustered nature of the data. All analyses were undertaken using SAS software version 9.3 [14].
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