Evaluating the performance of the GeneXpert HIV-1 qualitative assay as a consecutive test for a new early infant diagnosis algorithm in South Africa.

BACKGROUND: The proportion of HIV-exposed infants and young children infected with HIV in South Africa (SA) has declined markedly over the past decade as a result of the country's comprehensive prevention of mother-to-child transmission programme. This decrease has in turn reduced the positive predictive value (PPV) of diagnostic assays, necessitating review of early infant diagnosis (EID) algorithms to ensure improved accuracy. OBJECTIVES: To evaluate the performance of the GeneXpert HIV-1 qualitative assay (Xpert EID) as a consecutive test for infants with an 'HIV-detected' polymerase chain reaction screening test at birth. METHODS: We retrospectively analysed a longitudinal cohort of HIV-exposed infants on whom birth testing was performed, using whole-blood ethylenediaminetetra-acetic acid samples, from four tertiary sites in Gauteng Province between June 2014 and December 2019. Birth samples from all infants with a Cobas AmpliPrep/Cobas TaqMan HIV-1 Qualitative Test v2.0 (CAP/CTM v2.0) HIV-detected screening test, a concurrent Xpert EID test and a subsequent confirmatory CAP/CTM v2.0 test on a separate specimen were included. Performance of the Xpert EID in predicting final HIV status was determined as proportions with 95% confidence intervals (CIs). A comparison of indeterminate CAP/CTM v2.0 results, as per National Health Laboratory Service resulting practice, with discordant CAP/CTM v2.0 v. Xpert EID results was performed. RESULTS: Of 150 infants who met the inclusion criteria, 6 (3.9%) had an Xpert EID result discordant with final HIV status: 5 (3.3%) were false negatives and 1 (0.7%) was false positive. As a consecutive test, the Xpert EID yielded a sensitivity of 96.5% (95% CI 92 - 98.9), specificity of 85.7% (95% CI 42.1 - 99.6), PPV of 99.3% (95% CI 95.7 - 99.9), negative predictive value of 54.5% (95% CI 32.5 - 74.9) and overall accuracy of 96.1% (95% CI 91.5 - 98.5). Using discordant CAP/CTM v2.0/Xpert EID results as criteria to verify indeterminate results instead of current practice would have reduced the number of indeterminate screening results by 42.1%, from 18 (12.6%) to 11 (7.2%), without increasing the false-positive rate. CONCLUSIONS: Addition of the Xpert EID as a consecutive test for specimens with an HIV-detected PCR screening result has the potential to improve the PPV and reduce the indeterminate rate, thereby reducing diagnostic challenges and time to final status, in SA's EID programme.

Maternal HIV viral load testing during pregnancy and postpartum care in Gauteng Province, South Africa.

BACKGROUND: Pregnant and breastfeeding women living with HIV (WLHIV) are a target population for elimination of mother-to-child transmission of HIV (eMTCT). However, there are limited data on maternal virological responses during pregnancy and the postpartum period in South Africa (SA). OBJECTIVES: To review compliance of viral load (VL) testing with national guidelines and suppression rates during pregnancy and up to 9  months postpartum among WLHIV delivering in four tertiary hospitals in Gauteng Province, SA. METHODS: All women who had a point-of-care HIV VL test using Xpert HIV-1 VL (Cepheid, USA) at delivery in four tertiary obstetric units in Gauteng between June 2018 and February 2020 were included. HIV VL tests of eligible women performed up to 9 months before and after delivery were extracted from the National Health Laboratory Service's Corporate Data Warehouse. Proportions of women delivering who had antenatal and postpartum VL tests performed and their suppression rates were determined and expressed as percentages. RESULTS: Of 4 989 eligible WLHIV (median age 31.1 years), 917 (18.4%) had a VL performed during the antenatal period; of these, 335 (36.5%) had a VL ≥50 copies/mL and 165 (18.0%) a VL ≥1 000 copies/mL. At delivery, 1 911 women (38.3%) had a VL ≥50 copies/mL and 1 028 (20.6%) a VL ≥1 000 copies/mL. Among 627 women (12.6%) with a VL test postpartum, 234 (37.3%) had a VL ≥50 copies/mL and 93 (14.8%) a VL ≥1 000 copies/mL. Overall, having a VL test performed during the antenatal period was associated with viral suppression at delivery and receiving a VL test postpartum (p<0.001). Women with a VL ≥50 copies/mL at delivery were more likely to be younger and to remain virally unsuppressed postpartum (p<0.001) compared with women with a VL <50 copies/mL. CONCLUSIONS: Fewer than 5% of WLHIV with a VL at the time of delivery received VL monitoring during the antenatal and postpartum periods in accordance with national guidelines. More than 80% of WLHIV delivering had no evidence of VL monitoring during the antenatal period, and they were more likely than women who received monitoring during the antenatal period to be virally unsuppressed at delivery and to receive no VL monitoring postpartum. Women with a high VL at delivery were likely to remain virally unsuppressed postpartum. These results emphasise the need for closer monitoring of and rapid reaction to high maternal VLs during pregnancy, at delivery and postpartum for attainment of eMTCT.