Drug resistance among newly diagnosed HIV-infected children in the era of more efficacious antiretroviral prophylaxis.

BACKGROUND: In the era of more efficacious prevention of mother-to-child transmission (PMTCT) regimens, documenting the profile of drug resistance in HIV-infected infants and young children is critical to our efforts to improve care and treatment for children. METHODS: HIV drug resistance mutations in plasma virus were ascertained using population sequencing among 230 newly diagnosed HIV-infected children under 2 years of age recruited in Johannesburg, South Africa, during 2011. By this time, more effective PMTCT regimens, including combination antiretroviral therapy for pregnant women, were being implemented. RESULTS: Two-thirds (67.4%) of HIV-infected children had been exposed to some form of maternal (89%) and/or infant (97%) PMTCT. Among PMTCT-exposed, 56.8% had nonnucleoside reverse transcriptase inhibitor (NNRTI), 14.8% nucleoside reverse transcriptase inhibitor (NRTI), and 1.3% protease inhibitor mutations. NNRTI mutations were strongly related to younger age. The remaining third (32.6%) had no reported or recorded PMTCT exposures, but resistance to NNRTI was detected in 24.0%, NRTI in 10.7%, and protease inhibitor in 1.3%. CONCLUSION: The new PMTCT strategies dramatically reduce the number of children who acquire infection, but among those who do become infected, NNRTI resistance prevalence is high. In this South African setting with high PMTCT coverage, almost a quarter of children with no reported or recorded PMTCT also have drug resistance mutations. PMTCT history is an inadequate means of ruling out pretreatment drug resistance. Our results support the use of protease inhibitor-based first-line regimens in HIV-infected infants and young children regardless of PMTCT history.

Timing of maternal HIV testing and uptake of prevention of mother-to-child transmission interventions among women and their infected infants in Johannesburg, South Africa.

BACKGROUND: By 2011, South African prevention of mother-to-child transmission (PMTCT) of HIV programs had reduced perinatal HIV transmission at 6 weeks of age to 2.7%. We investigated the profile of newly diagnosed vertically infected children and their mothers to identify shortfalls in the PMTCT program. METHODS: In this operational follow-up study, fieldworkers enrolled mothers of newly diagnosed HIV-infected children up to 2 years of age at 5 major health care facilities in Johannesburg. Structured questionnaires and clinical record reviews were conducted and analyzed to describe the population and assess factors associated with PMTCT uptake. RESULTS: Two hundred eighty-nine mother-child pairs were enrolled. Timing of maternal HIV diagnosis influenced PMTCT access and feeding choices and was associated with infants' age at HIV diagnosis (7 vs. 11 vs. 31 weeks where mothers tested before, during, or after the pregnancy, respectively; P < 0.0001). Women diagnosed before pregnancy (12%) were older (median, 31 years) than those diagnosed during the index pregnancy (53%; median, 27 years). Women diagnosed after delivery (35%) were younger (median, 25 years, P < 0.0001), of lower parity, and less likely to be South African citizens. In 81 cases (29%), late maternal diagnosis precluded any PMTCT access. Where women were diagnosed during or before pregnancy, the recommended PMTCT guidelines for mother and infant were followed in 86 (61%) pairs. CONCLUSIONS: Failure to diagnose maternal HIV infection before delivery was the main reason for missing PMTCT prophylaxis and early infant testing. Timely maternal diagnosis enables PMTCT uptake, but implementation and follow-up gaps require attention to improve infant outcomes.

Application of PCR-LDR-nucleic acid detection strip in detection of YMDD mutation in hepatitis B patients treated with lamivudine.

Chronic hepatitis B virus (CHBV) infection causes cirrhosis and hepatocellular carcinoma. Lamivudine (LAM) has been successfully used to treat CHBV infections but prolonged use leads to the emergence of drug-resistant variants. This is primarily linked to a mutation in the tyrosine-methionine-aspartate-aspartate (YMDD) motif of the HBV polymerase gene at position 204. Rapid diagnosis of drug-resistant HBV is necessary for a prompt treatment response. Common diagnostic methods such as sequencing and restriction fragment length polymorphism (RFLP) analysis lack sensitivity and require significant processing. The aim of this study was to demonstrate the usefulness of a novel diagnostic method that combines polymerase chain reaction (PCR), ligase detection reaction (LDR) and a nucleic acid detection strip (NADS) in detecting site-specific mutations related to HBV LAM resistance. We compared this method (PLNA) to direct sequencing and RFLP analysis in 50 clinical samples from HBV infected patients. There was 90% concordance between all three results. PLNA detected more samples containing mutant variants than both sequencing and RFLP analysis and was more sensitive in detecting mixed variant populations. Plasmid standards indicated that the sensitivity of PLNA is at or below 3,000 copies per ml and that it can detect a minor variant at 5% of the total viral population. This warrants its further development and suggests that the PLNA method could be a useful tool in detecting LAM resistance.