Objective: The worldwide incidence of pregnancy for women living with perinatal HIV infection is increasing. Subsequently, there is growing risk of second-generation mother-to-child HIV transmission. The infant clinical outcomes for such a phenomenon have yet to be described.Design: As part of a wider observational study in KwaZulu-Natal, South Africa, six infants with in-utero HIV infection were identified as being born to mothers with perinatal HIV infection.Methods: Blood results and clinical data were collected in the first 3 years of life. In two cases, sample availability allowed confirmation by phylogenetic analysis of grandmother-to-mother-to-child HIV transmission.Results: Outcomes were poor in all six cases. All six mothers had difficulty administering twice daily combination antiretroviral therapy to their infants due to difficulties with acceptance, disclosure, poor health and being themselves long-term nonprogressors. Nonnucleoside reverse transcriptase inhibitor-resistant virus was detected in all mothers tested. None of the infants maintained suppression of viraemia on combination antiretroviral therapy. One infant died, and another was lost to follow-up. Conclusion:As the numbers of second-generation mother-to-child transmissions increase, it is important to highlight that this mother-infant dyad represents an extremely vulnerable group. In order for them to survive and thrive, these infants' mothers require their specific needs to be addressed and given intensive support.
Background: HIV and hepatitis B virus (HBV) prevalence are high in KwaZulu-Natal (KZN), South Africa. HIV co-infection negatively impacts HBV prognosis, and can increase likelihood of HBV mother-to-child-transmission (MTCT). In an established early treatment intervention cohort of HIV-transmitting mother-child pairs in KZN, we characterised HBV serological makers in mothers, and screened at-risk infants for HBV. Methods: Maternal samples (n=175) were screened for HBV infection (HBsAg), exposure to HBV (anti-HBc) and vaccination responses (anti-HBs-positive without other HBV markers). Infants of HBV-positive mothers were screened for HBsAg at 1 and 12 months. Results: HBV infection was present in 8.6% (15/175) of mothers. Biomarkers for HBV exposure were present in 31.4% (55/175), but absent in 53.3% (8/15) maternal HBV-positive cases. Maternal HBV vaccination appeared rare (8.0%; 14/175). Despite prescription of antiretroviral therapy (ART) active against HBV, HBV DNA was detectable in 46.7% (7/15) HBsAg-positive mothers, with (5/7) also viraemic for HIV. Three mothers had HBV viral loads >5.3log10 IU/ml, making them high-risk for HBV MTCT. Screening of available infant samples at one month of age (n=14) found no cases of HBV MTCT, and at 12 months (n=13) identified one HBV infection. Serological vaccination evidence was present in 53.8% (7/13) infants tested. Discussion: This vulnerable cohort of HIV-transmitting mothers had a high undiagnosed HBV prevalence. Early infant ART may have reduced risk of MTCT in high-risk cases. Current HBV guidelines recommend antenatal antiviral prophylaxis but these data underline a potential role for infant post-exposure prophylaxis in high-risk MTCT pairs, warranting further investigation.
Point-of-care (PoC) testing facilitates early infant diagnosis (EID) and treatment initiation, which improves outcome. We present a field evaluation of a new PoC test (Cepheid Xpert® HIV-1 Qual XC RUO) to determine whether this test improves EID and assists the management of children living with human immunodeficiency virus (HIV) infection.We compared 2 PoC tests with the standard-of-care (SoC) test used to detect HIV infection from dry blood spots in newborn infants at high risk of in utero infection. We also evaluated the ability of the PoC tests to detect HIV total nucleic acid (TNA) in children living with HIV infection who had maintained undetectable plasma viremia following very early combination antiretroviral therapy (cART) initiation.Qualitative (Qual) detection of HIV using the Xpert® HIV-1 Qual XC RUO ("RUO") and Xpert® HIV-1 Qual ("Qual") PoC tests was compared in 224 infants with the SoC DBS Roche COBAS® HIV-1/HIV-2 qualitative test. The same 2 PoC tests were also evaluated in 35 older children who had initiated cART before 21 days of age and maintained undetectable plasma viremia for a mean of 25 months.No discrepancies were observed in detection of HIV infection via the 2 PoC tests or the SoC test in the 224 neonates studied, but only 95% of the SoC test results were generated compared with 100% of the PoC test results (P = .0009). The cycle threshold values for the research use only (RUO) assay were the lowest of the 3 assays (P < .0001 in each case). In 6 of the 35 early-treated aviremic children, HIV TNA was detected by RUO but not Qual.The RUO assay outperforms Qual in detecting HIV-1 infection. RUO would therefore potentially improve EID and assist in identifying cART-adherent early-treated children with the lowest HIV TNA levels and the highest HIV cure potential. Abbreviations: ART = combination antiretroviral therapy, Ct = cycle threshold, DBS = dry blood spot, EID = early infant diagnosis, HIV = human immunodeficiency virus, PBMC = peripheral blood mononuclear cell, PoC = point-of-care, Qual = qualitative, RUO = research use only, SoC = standard of care, TNA = total nucleic acid.
Background HIV and hepatitis B virus (HBV) prevalence are high in KwaZulu-Natal, South Africa. HIV co-infection negatively impacts HBV prognosis, and can increase likelihood of HBV mother-to-child-transmission (MTCT). In an early HIV infant treatment intervention cohort of HIV-transmitting mother-child pairs in KwaZulu-Natal, we characterised maternal HBV prevalence, and screened at-risk infants. Methods Infants were treated for HIV MTCT at birth, and combination regimens incidentally active against HBV were initiated within 21 days. Maternal samples (n = 175) were screened for HBV infection (HBsAg), exposure to HBV (anti-HBc) and vaccination responses (anti-HBs-positive without other HBV markers) at birth. Infants of HBV-positive mothers were screened for HBsAg at 1 and 12 months. Results Evidence of HBV infection was present in 8.6% (15/175) of maternal samples. Biomarkers for HBV exposure were present in 31.4% (55/175). Evidence of HBV vaccination was uncommon in mothers (8.0%; 14/175). Despite prescription of antiretroviral therapy (ART) active against HBV, HBV DNA was detectable in 46.7% (7/15) HBsAg-positive mothers. Three mothers had HBV viral loads >5.3log10 IU/ml, making them high-risk for HBV MTCT. Screening of available infant samples at one month (n = 14) found no cases of HBV MTCT. At 12 months, we identified one HBV infection (1/13) and serological evidence of vaccination was present in 53.8% (7/13) infants. Discussion This vulnerable cohort of HIV-transmitting mothers had a high undiagnosed HBV prevalence. Early infant ART may have reduced risk of MTCT in high-risk cases. Current HBV guidelines recommend ART prophylaxis but these data underline the pressing need to increase availability of birth dose vaccines.
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