Impact of breastfeeding, maternal antiretroviral treatment and health service factors on 18-month vertical transmission of HIV and HIV-free survival: results from a nationally representative HIV-exposed infant cohort, South Africa.

BACKGROUND: We analysed the impact of breastfeeding, antiretroviral drugs and health service factors on cumulative (6 weeks to 18 months) vertical transmission of HIV (MTCT) and 'MTCT-or-death', in South Africa, and compared estimates with global impact criteria to validate MTCT elimination: (1) <5% final MTCT and (2) case rate ≤50 (new paediatric HIV infections/100 000 live births). METHODS: 9120 infants aged 6 weeks were enrolled in a nationally representative survey. Of 2811 HIV-exposed uninfected infants (HEU), 2644 enrolled into follow-up (at 3, 6, 9, 12, 15 and 18 months). Using Kaplan-Meier analysis and weighted survey domain-based Cox proportional hazards models, we estimated cumulative risk of MTCT and 'MTCT or death' and risk factors for time-to-event outcomes, adjusting for study design and loss-to-follow-up. RESULTS: Cumulative (final) MTCT was 4.3% (95% CI 3.7% to 5.0%); case rate was 1290. Postnatal MTCT (>6 weeks to 18 months) was 1.7% (95% CI 1.2% to 2.4%). Cumulative 'MTCT-or-death' was 6.3% (95% CI 5.5% to 7.3%); 81% and 62% of cumulative MTCT and 'MTCT-or-death', respectively, occurred by 6 months. Postnatal MTCT increased with unknown maternal CD4-cell-count (adjusted HR (aHR 2.66 (1.5-5.6)), undocumented maternal HIV status (aHR 2.21 (1.0-4.7)) and exclusive (aHR 2.3 (1.0-5.2)) or mixed (aHR 3.7 (1.2-11.4)) breastfeeding. Cumulative 'MTCT-or death' increased in households with 'no refrigerator' (aHR 1.7 (1.1-2.9)) and decreased if infants used nevirapine at 6 weeks (aHR 0.4 (0.2-0.9)). CONCLUSIONS: While the <5% final MTCT target was met, the case rate was 25-times above target. Systems are needed in the first 6 months post-delivery to optimise HEU health and fast-track ART initiation in newly diagnosed mothers.

Enhancing HIV Treatment Access and Outcomes Amongst HIV Infected Children and Adolescents in Resource Limited Settings.

Introduction Increasing access to HIV-related care and treatment for children aged 0-18 years in resource-limited settings is an urgent global priority. In 2011-2012 the percentage increase in children accessing antiretroviral therapy was approximately half that of adults (11 vs. 21 %). We propose a model for increasing access to, and retention in, paediatric HIV care and treatment in resource-limited settings. Methods Following a rapid appraisal of recent literature seven main challenges in paediatric HIV-related care and treatment were identified: (1) lack of regular, integrated, ongoing HIV-related diagnosis; (2) weak facility-based systems for tracking and retention in care; (3) interrupted availability of dried blood spot cards (expiration/stock outs); (4) poor quality control of rapid HIV testing; (5) supply-related gaps at health facility-laboratory interface; (6) poor uptake of HIV testing, possibly relating to a fatalistic belief about HIV infection; (7) community-associated reasons e.g. non-disclosure and weak systems for social support, resulting in poor retention in care. Results To increase sustained access to paediatric HIV-related care and treatment, regular updating of Policies, review of inter-sectoral Plans (at facility and community levels) and evaluation of Programme implementation and impact (at national, subnational, facility and community levels) are non-negotiable critical elements. Additionally we recommend the intensified implementation of seven main interventions: (1) update or refresher messaging for health care staff and simple messaging for key staff at early childhood development centres and schools; (2) contact tracing, disclosure and retention monitoring; (3) paying particular attention to infant dried blood spot (DBS) stock control; (4) regular quality assurance of rapid HIV testing procedures; (5) workshops/meetings/dialogues between health facilities and laboratories to resolve transport-related gaps and to facilitate return of results to facilities; (6) community leader and health worker advocacy at creches, schools, religious centres to increase uptake of HIV testing and dispel fatalistic beliefs about HIV; (7) use of mobile communication technology (m-health) and peer/community supporters to maintain contact with patients. Discussion and Conclusion We propose that this package of facility, community and family-orientated interventions are needed to change the trajectory of the paediatric HIV epidemic and its associated patterns of morbidity and mortality, thus achieving the double dividend of improving HIV-free survival.

Population-level effectiveness of PMTCT Option A on early mother-to-child (MTCT) transmission of HIV in South Africa: implications for eliminating MTCT.

BACKGROUND: Eliminating mother-to-child transmission of HIV (EMTCT), defined as ≤50 infant HIV infections per 100 000 live births, is a global priority. Since 2011 policies to prevent mother-to-child transmission of HIV (PMTCT) shifted from maternal antiretroviral (ARV) treatment or prophylaxis contingent on CD4 cell count to lifelong maternal ARV treatment (cART). We sought to measure progress with early (4-8 weeks postpartum) MTCT prevention and elimination, 2011-2013, at national and sub-national levels in South Africa, a high antenatal HIV prevalence setting ( ≈ 29%), where early MTCT was 3.5% in 2010. METHODS: Two surveys were conducted (August 2011-March 2012 and October 2012-May 2013), in 580 health facilities, randomly selected after two-stage probability proportional to size sampling of facilities (the primary sampling unit), to provide valid national and sub-national-(provincial)-level estimates. Data collectors interviewed caregivers of eligible infants, reviewed patient-held charts, and collected infant dried blood spots (iDBS). Confirmed positive HIV enzyme immunoassay (EIA) and positive total HIV nucleic acid polymerase chain reaction (PCR) indicated infant HIV exposure or infection, respectively. Weighted survey analysis was conducted for each survey and for the pooled data. FINDINGS: National data from 10 106 and 9120 participants were analyzed (2011-12 and 2012-13 surveys respectively). Infant HIV exposure was 32.2% (95% confidence interval (CI) 30.7-33.6%), in 2011-12 and 33.1% (95% CI 31.8-34.4%), provincial range of 22.1-43.6% in 2012-13. MTCT was 2.7% (95% CI 2.1%-3.2%) in 2011-12 and 2.6% (95% CI 2.0-3.2%), provincial range of 1.9-5.4% in 2012-13. HIV-infected ARV-exposed mothers had significantly lower unadjusted early MTCT (2.0% [2011-12: 1.6-2.5%; 2012-13:1.5-2.6%]) compared to HIV-infected ARV-naive mothers [10.2% in 2011-12 (6.5-13.8%); 9.2% in 2012-13 (5.6-12.7%)]. Pooled analyses demonstrated significantly lower early MTCT among exclusive breastfeeding (EBF) mothers receiving >10 weeks ARV prophylaxis or cART compared with EBF and no ARVs: (2.2% [95% CI 1.25-3.09%] vs 12.2% [95% CI 4.7-19.6%], respectively); among HIV-infected ARV-exposed mothers, 24.9% (95% CI 23.5-26.3%) initiated cART during or before the first trimester, and their early MTCT was 1.2% (95% CI 0.6-1.7%). Extrapolating these data, assuming 32% EIA positivity and 2.6% or 1.2% MTCT, 832 and 384 infants per 100 000 live births were HIV infected, respectively. CONCLUSIONS: Although we demonstrate sustained national-level PMTCT impact in a high HIV prevalence setting, results are far-removed from EMTCT targets. Reducing maternal HIV prevalence and treating all maternal HIV infection early are critical for further progress.