Prevalence and outcomes of HIV‐1 diagnostic challenges during universal birth testing – an urban South African observational cohort

Abstract

Introduction: HIV-1 polymerase chain reaction (PCR) testing at birth aims to facilitate earlier initiation of antiretroviral therapy (ART) for HIV-infected neonates. Data from two years of universal birth testing implementation in a high-burden South African urban setting are presented to demonstrate the prevalence and outcomes of diagnostic challenges in this context. Methods: HIV-exposed neonates born at Rahima Moosa Mother and Child Hospital between 5 June 2014 and 31 August 2016 were routinely screened at birth for HIV-1 on whole blood samples using the COBAS® AmpliPrep/COBAS® TaqMan (CAP/CTM) HIV-1 Qualitative Test, version 2.0 (Roche Molecular Systems, Inc., Branchburg, NJ, USA). Virological results were interpreted according to standard operating procedures with the South African National Health Laboratory Service. All neonates with non-negative results were actively followed-up and categorized according to HIV infection status as positive, negative, uncertain and lost to follow-up (LTFU). Results: 104 (1.8%) of 5743 HIV-exposed neonates received a non-negative birth PCR result, for which laboratory data were available for 102 (98%) cases – 78 (76%) tested positive and 24 (24%) indeterminate. HIV infection status was confirmed positive in 83 (81%) infants, negative in 8 (8%), uncertain in 5 (5%) and LTFU in 6 (6%) cases. The positive predictive value (excluding cases of uncertain diagnosis and inadequate testing) following a non-negative HIV-1 PCR screening test at birth was 0.91 (83/91; 95% confidence interval: 0.85–0.96). Neonates testing positive at birth had significantly higher viral load (VL) results than those testing indeterminate at birth of 4.5 and 3.0 log copies/ml (p = 0.0007), respectively. Similarly, mothers of neonates with positive as compared to indeterminate birth test results had higher VLs of 4.5 and 2.7 log copies/ml (p = 0.0013), respectively. Half of neonates with an indeterminate birth test were shown to be HIV-infected on subsequent confirmatory testing, with time to final diagnosis 30 days longer for these neonates (p < 0.0001). Conclusion: Indeterminate HIV-1 PCR results accounted for a quarter of non-negative results at birth and were associated with a high risk of infection in comparison to the risk of in utero transmission. Indeterminate birth results with positive HIV PCR results on repeat testing were associated with later final diagnosis. The HIV-1 status remains uncertain in a minority of cases because of repeatedly indeterminate results, highlighting the need for more sensitive and specific virological tests.

Leveraging the Road to Health booklet as a unique patient identifier to monitor the prevention of mother-to-child transmission programme

“…Furthermore, the additional column populating the RTHB identifiers incorporated in the consolidated weekly HIV PCR Results for Action Report, allowed continuous monitoring of uptake and usage of RTHB identifiers among all of the public health facilities in the district. Interestingly, the intra-uterine and intrapartum infection rates among the RTHB identifier cohort are similar to near-contemporaneous birth cohorts described in SA, [7,8] supporting the potential use of RTHB identifiers for EID surveillance.…”

Monitoring diagnosis, retention in care and viral load suppression in children testing HIV polymerase chain reaction-positive in two districts in South Africa

“…This change has resulted in an increase in indeterminate and discordant HIV PCR and VL results that complicate making a definitive diagnosis of HIV in children. [16][17][18] Longitudinal cohort monitoring of HIV-infected children receiving HIV care is crucial for evaluating programme performance and adapting interventions to reduce gaps along the HIV care continuum. The National Department of Health uses Tier.net, an electronic patient management system for HIV-infected patients accessing HIV treatment in the public sector in SA.…”

Mother-to-Child HIV Transmission Factors in Exposed Children at University Hospital Center of Treichville (Abidjan, Cote d’Ivoire)

“…Thus, Martin [10] in Angola and Technau [11] in South Africa, reported in their studies, the respective mother-child transmission rates of 4.1% and 1.8%. It should be noted that the reported rates in the majority of studies conducted in countries with limited resources, are generally higher than 10% [12] [13] [14].…”