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Objectives: We examined uptake of prevention of mother-to-child HIV transmission (PMTCT) services, predictors of missed opportunities, and infant HIV transmission attributable to missed opportunities along the PMTCT cascade across South Africa. Methods: A cross-sectional survey was conducted among 4-8 week old infants receiving first immunisations in 580 nationally representative public health facilities in 2010. This included maternal interviews and testing infants’ dried blood spots for HIV. A weighted analysis was performed to assess uptake of antenatal and perinatal PMTCT services along the PMTCT cascade (namely: maternal HIV testing, CD4 count test/result, and receiving maternal and infant antiretroviral treatment) and predictors of dropout. The population attributable fraction associated with dropouts at each service point are estimated. Results: Of 9,803 mothers included, 31.7% were HIV-positive as identified by reactive infant antibody tests. Of these 80.4% received some form of maternal and infant antiretroviral treatment. More than a third (34.9%) of mothers dropped out from one or more steps in the PMTCT service cascade. In a multivariable analysis, the following characteristics were associated with increased dropout from the PMTCT cascade: adolescent (<20 years) mothers, low socioeconomic score, low education level, primiparous mothers, delayed first antenatal visit, homebirth, and non-disclosure of HIV status. Adolescent mothers were twice (adjusted odds ratio: 2.2, 95% confidence interval: 1.5-3.3) as likely to be unaware of their HIV-positive status and had a significantly higher rate (85.2%) of unplanned pregnancies compared to adults aged ≥20 years (55.5%, p = 0.0001). A third (33.8%) of infant HIV infections were attributable to dropout in one or more steps in the cascade. Conclusion: A third of transmissions attributable to missed opportunities of PMTCT services can be prevented by optimizing the uptake of PMTCT services. Identified risk factors for low PMTCT service uptake should be addressed through health facility and community-level interventions, including raising awareness, promoting women education, adolescent focused interventions, and strengthening linkages/referral-system between communities and health facilities.
A cross-sectional survey was conducted from June-December 2010 among mother/caregiver-infant pairs visiting the immunisation service points of randomly selected public primary health care facilities (PHCs) and community health centres (CHCs) across the nine provinces of South Africa. The protocol and overall transmission rate findings have been published elsewhere.[8] At the time of the study guidelines in South Africa recommended that mothers be offered Zidovudine (AZT) from 28 weeks gestation and single dose nevirapine (sdNVP) at labour or triple (combination) antiretroviral therapy (cART) if CD4 cell count was ≤200 cells/mm3. Infants were offered sdNVP at birth and 7–28 days of postpartum AZT.[16] The sample size was calculated taking into account the 2009 antenatal HIV prevalence data[17], transmission rate estimates from two previous sub-national surveys[18, 19], and the coverage of ARV prophylaxis in each province from district health information system (DHIS) reports. A precision-based sample size was calculated for varying MTCT precision levels by province (ranging from 1% to 2%) and a design effect of 2 to account for clustering within health facilities. Based on this, the collection of interview data and infant dried blood spots (DBS) from 12,200 mother-infant pairs was needed to provide stable provincial and national level estimates of transmission rates and PMTCT services uptake. Further details on parameters used for sample size calculation are presented elsewhere.[6] The sampling frame comprised all public PHCs and CHCs throughout the country. Small facilities (with <130 annual Diptheria-Pertussis-Tetatus-1 (DTP1) immunisations) were excluded from the sampling frame [the proportion of annual six-week immunisation done in small facilities in 2007 was only 6.7%]. A multistage stratified cluster sampling method was used to select facilities. The 2007 DHIS immunisation data and the 2009 antenatal HIV prevalence estimates were used to stratify facilities into three groups: medium-sized facilities with 130–300 annual DTP1 immunisation number, large (≥ 300 annual DTP 1 immunisation number) facilities with HIV prevalence below the national HIV prevalence estimate (<29%), and large facilities with HIV prevalence ≥29%. A probability proportional to size sampling method was used to select 580 medium and large size facilities with both high and low HIV prevalence. At the final step, a fixed number (proportional to facility size) of individual mother-infant pairs were sampled consecutively from each selected facility within a specified period of time [3 (in 8 provinces) to 4 (in 1 province) weeks was spent in each facility]. Mother/caregiver-infant pairs at selected facilities were approached and screened for eligibility. Inclusion criteria were infants aged 4-8weeks, with no emergency illness and receiving their six-week immunisation on the visit day. Consented mothers were interviewed on antenatal and obstetric history, knowledge about PMTCT, history of antenatal HIV testing, HIV status, CD4 count testing and ARV services received. PMTCT-related questions were answered by biological mothers only. Interview data were collected on hand-held devices (cell phone pre-programmed questionnaire). After the interview, individual pre-test counselling was given to each mother and if mothers consented, DBS were collected from infants using heel-prick. DBS specimens were tested for HIV antibodies by means of an enzyme immunoassay (EIA) (Genscreen HIV1/2 Ab EIA Version 2, Bio-Rad Laboratories, France). A positive EIA result indicated infant HIV exposure. A qualitative HIV polymerase chain reaction (PCR) (COBAS AmpliPrep/COBAS TaqMan (CAP/CTM) Qualitative assay version 1.0 assay, Roche Diagnostics, Branchburg, NJ) test was performed on all EIA-positive DBS to determine whether the infant was HIV PCR-positive (i.e. HIV-infected). Infants were included in this analysis if they had both maternal interviews on the PMTCT sections of the questionnaire and complete laboratory results for HIV testing (i.e. EIA test result was needed from all infants and for EIA-positive infants PCR test result was needed in order to be included in the analysis). Mothers who had an EIA-positive infant were considered to be HIV-positive. We identified four PMTCT cascade steps (also referred as ‘PMTCT cascade indicators’): maternal HIV-positive status knowledge (reporting HIV-positive status determined before or during pregnancy), maternal CD4 cell count testing and receipt of result, receipt of maternal ARV and infant nevirapine (NVP). The denominator for each of the 4 indicators was “total number of HIV-positive mothers, as identified from infant EIA test”. Dropout was calculated as a proportion of HIV-positive mothers who missed a step in the cascade regardless of returning to receive subsequent services. Mothers who miss multiple steps are considered as dropout only once, at their first missed step. Dropout does not take poor adherence into consideration; rather it only included instances where mother-infant pairs did not access a given service. We compared categorical responses using chi-square tests. Multivariable regression analysis was used to identify factors associated with missed opportunities and dropouts in the following PMTCT cascade indicators: (1) maternal HIV-positive status knowledge (2) CD4 cell count testing and receipt of result (as a single outcome of interest), and (3) an overall indicator for “at least one dropout at any of the four PMTCT cascade steps”. Initial univariable analysis included explanatory variables identified in similar studies and those with biological plausibility. All variables with a p-value below 0.2 were included in the starting variable set for multivariable regression. From a multivariable model, factors were dropped if they were non-significant (at p 0.05) and did not markedly alter (by 10% or more) estimates of other significant variables in the model. We created a socio-economic score from availability of assets (television, car, refrigerator, stove), and dwelling characteristics (type of water, toilet, fuel and building material) using the principal component analysis method. In order to assess the potential for prevention, this study used the method explained by Basu and Landis to estimate PAF.[20] Two types of PAF were estimated. The first PAF was estimated assuming that prevention efforts/interventions target each cascade step separately; the estimated PAF from this step reflects the transmission preventable by eliminating missed opportunities from one cascade step. The second PAF—which we refer as cumulative PAF- was estimated assuming prevention interventions target 2, 3 or all 4 cascade steps at once. We report incidence reductions that correspond to the cumulative PAF. To estimate both the PAF and the cumulative PAF, 8 models (1 PAF model and 1 cumulative PAF model for each of the 4 cascade steps) were fitted at each of the four PMTCT cascade indicators and the outcome ‘infant HIV infection’. Each model was adjusted for potential covariates from the literature, which included maternal age (10 year age groups), education (below secondary), socioeconomic score (the two lowest quintiles, middle and fourth quintile, vs. fifth/highest quintile), feeding pattern (exclusive breastfeeding or no breastfeeding vs. mixed breastfeeding), number of children (1, 2, ≥3), and type of delivery (caesarean section or vaginal delivery). Intermediary factors that are on the causal pathway between the PMTCT cascade indicators and HIV transmission risk were not included in the analysis. Covariates with missing data used for adjusting the PAF models were imputed sequentially using Monte Carlo multiple imputation technique. Cascade indicators with missing data were not imputed as the missing responses of these indicators are correlated. We had 4.7%, 1.4% and 2.2% missing responses for CD4 count testing, and maternal and infant ARV initiation indicators, respectively. The PAF estimates were analysed using all available data. The cumulative PAF was estimated using complete case analysis by excluding observations with missing cascade indicator data. Analyses were done using STATA SE (version 12, Texas, 77845 USA) and were adjusted for the complex survey design, including sample size realization, clustering and the 2010 live-birth distribution across provinces. The study protocol was approved by the United States Centers for Disease Control and Prevention and the institutional review board of the Medical Research Council of South Africa. All study participants provided written informed consent.
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