Vertical transmission of HIV among pregnant women who initially had false–negative rapid HIV tests in four South African antenatal clinics

INTRODUCTION : There is a risk of mother-to-child transmission of HIV (MTCT) during pregnancy and breastfeeding. The aim of this study was to assess vertical transmission of HIV among pregnant women who initially had false–negative rapid HIV tests in South African antenatal care (ANC) clinics. METHODS : Pregnant participants were enrolled in a diagnostic study that used nucleic acid amplification testing (NAAT) to screen for early HIV infection among individuals who tested negative on rapid HIV tests used at the point-of-care (POC) facilities. Participants were enrolled from four ANC clinics in the Tshwane district of South Africa. All NAAT-positive participants were recalled to the clinics for further management. Vertical transmission was assessed among exposed infants whose HIV polymerase chain reaction (PCR) results were available. RESULTS : This study enrolled 8208 pregnant participants who tested negative on rapid HIV tests between 2013 and 2016. Their median age was 26 years (interquartile range [IQR]: 23–30). NAAT detected HIV infections in 0.6% (n = 49; 95% confidence interval {CI}: 0.5–0.8) of all study participants. The distribution of these infections among the four clinics ranged from 0.3%– 1.1%, but this was not statistically significant (p = 0.07). Forty-seven participants (95.9%) were successfully recalled and referred for antiretroviral treatment initiation as part of prevention of MTCT (PMTCT). Most women with newly diagnosed HIV infection presented for the first ANC visit in the second (61.9%, n = 26) and third (31.0%, n = 13) trimesters. HIV PCR results were available for thirty-two infants, three of whom tested positive (9.4%; 95% CI: 1.98–25.02). CONCLUSIONS : This study showed that supplemental HIV testing for pregnant women led to earlier linkage to the PMTCT programme. Inaccurate diagnosis of HIV infection at ANC clinics is likely to undermine the efforts of eliminating MTCT particularly in HIV-endemic settings.S1 Table. Characteristics of participants diagnosed with early or chronic HIV infection. Initial tests were performed from samples obtained at enrolment (i.e. after a negative rapid HIV test result). HIV viral load (VL) tests were performed first to screen for HIV infection, and all the serology tests were performed later. Follow-up (F/U) VL was only performed for participants who had an initial VL <5000 copies/ml [16]. Pt ID = participant’s study identity, F = female, gen = generation, ELISA = enzyme-linked immunosorbent assay, W. Blot = Western Blot, LAg = limiting antigen, Insuf = insufficient, LT = long term (chronic) infection, --- = not available (participant did not return for follow-up), + = positive,— = negative. Units: HIV VL = copies/ml; p24 antigen = cut-off index (COI); Genscreen ELISA = sample cut-off (S/CO); LAg avidity = normalized optical density (OD-n); LAg avidity <1.5 OD-n = early infection; LAg avidity >1.5 OD-n = LT (chronic) infection. ¥ = participant 6738 was previously misclassified as having chronic infection [16], but testing on her follow-up sample revealed low avidity antibodies consistent with early infection; this was confirmed on repeat testing of 6738 sample. P24 antigen, W. Blot and F/U LAg were not performed for the last participants identified with newly diagnosed HIV infection owing to cost limitations. This also applies to the F/U VL for participant 1692, as this was supposed to have been performed according to the diagnostic study protocol [14].This work was supported by SHM - South African Medical Research Council – Self Initiated Research (SA MRC-SIR) grant; SHM - Discovery Foundation grant; SHM - Hamilton Naki Clinical Scholarship; and TCQ - The Division of Intramural Research, NIAID, NIH.SHM - South African Medical Research Council – Self Initiated Research (SA MRC-SIR) grant; SHM - Discovery Foundation grant; SHM - Hamilton Naki Clinical Scholarship; and TCQ - The Division of Intramural Research, NIAID, NIH.http://www.plosone.orgam2020Internal Medicin