A longitudinal analysis of neonatal and infant diagnostic HIV-PCR uptake and associations during three sequential policy periods in Mitchell’s Plain, Cape Town

Abstract

Background: Despite technological and programmatic advances in the prevention of vertical transmission of HIV and early infant diagnosis (EID), paediatric HIV continues to have a significant impact on infant and child survival in low- and middle-income countries. Many EID programmes follow the WHO recommendation of initial infant HIV testing with a nucleic acid assay at 4-6 weeks old. In general this strategy has been poorly implemented with substantial attrition after birth such that, according to UNAIDS, only 51% of HIV-exposed infants received a virological test in the first two months of life in 2015. In addition, there is concern about the sensitivity of the nucleic acid assays at six weeks in the context of exposure to prolonged multidrug antiretroviral therapy as infant post-exposure prophylaxis, and in breast milk. HIV-PCR testing at birth has been promoted as a means of maximizing the number of infants who receive an HIV test as well as identifying in utero-infected infants in whom HIV infection may follow an aggressive course. Evidence from pilot studies and modelling data was sufficiently compelling for the WHO to include a conditional recommendation for the addition of a birth HIV-PCR (either routine or targeted at high risk groups) to its EID algorithms in 2015. The Western Cape introduced targeted birth HIV testing for high risk infants in August 2014 and expanded this in line with the South African National Prevention of Mother-to-Child Transmission Guidelines, to include all HIV-exposed infants in December 2015. Methods: Between 2013 and 2016 we conducted an implementation science project to iteratively assess the implementation and effectiveness of the vertical transmission prevention of HIV in a chain of referral facilities in Cape Town (i.e. from primary to tertiary care). The e-register provided a single longitudinal record for each woman (linked to her infant after birth) and enabled assessment of HIV testing and treatment from first antenatal visit through delivery to infant HIV testing. Using a cohort of HIV-exposed live infants from this database, a protocol was designed (Section A: Protocol) to assess the implementation and outcome of effectively three different EID policy periods in the facility chain. i.e. an initial period of birth HIV-PCR at the clinician’s discretion if evidence of HIV infection; a period of targeted birth testing of high risk infants and lastly, of routine birth HIV-PCR for all HIV-exposed infants. A critical review of the literature appraised published assessments of birth HIV testing programmes in low- and middle-income countries (Section B: Literature Review) with the aim of assessing in utero transmission rates, follow-up testing and transmission rates and the resources required for implementation. Studies that modelled the impact of birth HIV testing were specifically reviewed. The manuscript (Section C: Manuscript) presented an analysis of the HIV-infected/exposed mother/infant dyads from the e-register of the Closing the Gaps study. Using this database adherence to guidelines in each period was assessed as well as the outcome of HIV-PCR at four delivery sites and the impact of the policies on return for follow-up EID. Results: South Africa is the first country in sub-Saharan Africa to implement birth HIV testing and most of the studies in support of this strategy were generated here. There was limited literature which highlighted the need for further investigation into the implementation and effectiveness of such programmes. No prospective data addressed targeted birth testing and those reporting on more routine birth HIV-PCR demonstrated success in timeous diagnosis and treatment although significant additional project resources were required. The retrospective laboratory data indicated that receipt of a birth HIV-PCR reduced the likelihood for follow-up at later testing time-points. This is important as the modelling studies suggested that the clinical and financial benefits of adding birth testing to existing algorithms would be lost if follow-up was poor. In the cohort of 2012 HIV-exposed infants in the study presented in the manuscript, the proportion who received birth testing increased with the progression of the EID policies but guideline implementation was poor, especially in primary care, with only 60% of infants being tested as recommended. The proportion of infants with positive HIV-PCR decreased as the pool of HIV-exposed infants undergoing testing expanded, being highest during the periods of targeted birth testing. In concurrence with the South African literature, receipt of a birth HIV-PCR decreased the likelihood of follow-up testing at 6-10 weeks. Among infants tested at 6-10 weeks old, the proportion who were positive for the first time at this time- point increased with the introduction of routine birth testing for all HIV-exposed infants, emphasizing the importance of the follow-up EID time-points. Conclusion: Virological testing at birth effectively increased the number of HIV-exposed infants who received an HIV test and was effective in identifying in utero infection in high risk infants (who could start treatment early with the attendant benefits.) The Western Cape EID policies were incompletely implemented in the study facilities over this time with many infants not being tested as indicated. Birth HIV-PCR decreased follow-up testing, an unintended consequence of serious concern. Adherence to the provincial and national guidelines needs to be re-enforced at delivery sites and at the primary care facilities where follow-up EID occurs