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Background: Combination antiretroviral drug regimens are increasingly preferred for neonatal postexposure prophylaxis (PEP) among HIV-exposed infants with high-risk of transmission. We evaluated the adverse events associated with the use of zidovudine (ZDV)/lamivudine (3TC)/nevirapine (NVP) for neonatal PEP during the first 6 weeks of life., Methods: A prospective cohort of non-breast-fed HIV-exposed infants was conducted at 5 clinical sites in Thailand. Study population included 100 high-risk HIV-exposed infants (maternal HIV RNA > 50 copies/mL prior to delivery or received antiretroviral therapy less than 12 weeks) and 100 low-risk HIV-exposed neonates. High-risk infants received ZDV/3TC/NVP for 6 weeks whereas low-risk HIV-exposed neonates received a 4-week regimen of ZDV. Complete blood count, aspartate transaminase and alanine transaminase were assessed at birth, 1, 2 and 4 months of life., Results: From October 2015 to November 2017, 200 infants were enrolled, of which 18.5% had low birth weight < 2500 g. The proportion of infants with anemia grade 2 or higher at 1 and 2 months of life between ZDV/3TC/NVP and ZDV prophylaxis was 48.5% vs 32.3% (P=0.02); nevertheless, severe anemia (grade 3) was not significantly different; 9.2% vs 10.2% (P=0.81), respectively. At 1 month old, infants on ZDV/3TC/NVP prophylaxis had significantly higher grade 2 anemia versus infants on ZDV alone (33.0% vs 13.4%; P=0.001); however, no difference was observed at 2 months old. No differences in neutropenia or hepatotoxicity between infant prophylactic regimens were observed., Conclusions: Triple antiretroviral neonatal PEP with ZDV/3TC/NVP for 6 weeks in high-risk HIV-exposed infants did not significantly increase the risk of short-term toxicity compared with ZDV-monotherapy prophylaxis.

Background: Triple-drug infant antiretroviral prophylaxis containing nevirapine (NVP) is increasingly used to prevent HIV transmission among neonates at high risk of HIV infection. Our aim was to describe NVP concentration from birth through the first month of life., Methods: High-risk HIV-exposed neonates were enrolled in a prospective cohort in Thailand. High-risk neonates defined as maternal HIV RNA >50 copies/mL before delivery or mother received antiretroviral treatment for <12 weeks before delivery. Neonates received zidovudine (4 mg/kg) and lamivudine (2 mg/kg) twice daily, plus NVP (4 mg/kg) once daily (no lead-in) from birth to 6 weeks of life. Infant plasma samples were collected at 1, 2, 14 or 2, 7, 28 days of life. NVP trough concentrations (C24) were estimated using a population pharmacokinetic model and target C24 was ≥0.1 mg/L. "Washout" efavirenz (EFV) concentrations were assessed in infants whose mother received EFV-based antiretroviral treatment., Results: A total of 48 infants were included: 25 (52%) were male and 12 (25%) were preterm (gestational age 34-37 weeks). Median (interquartile range) predicted NVP C24 were 1.34 mg/L (1.13-1.84), 2.24 (2.00-2.59), 2.78 (2.61-3.12), 2.20 (1.86-2.44) and 0.81 (0.58-0.98) on days 1, 2, 7, 14 and 28 of life, respectively. NVP C24 was not significantly different between term and preterm infants. All infants maintained NVP C24 ≥0.1 mg/L. EFV via placental transfer remained detectable in infants up to 7 days of life., Conclusions: NVP 4 mg/kg daily from birth provided adequate prophylactic concentrations during the first month of life in high-risk HIV-exposed neonates.

Background: Persistent renal dysfunction (PRD) has been reported in up to 22% of perinatally HIV-infected adolescents (PHAs) in the United States and Europe. There are limited data available on PRD among PHAs in resource-limited settings regarding access to antiretroviral therapy (ART) at more advanced HIV stages., Methods: We retrospectively described the prevalence of PRD and associated factors in a Thai PHA cohort. Inclusion criteria were current age ≥10 years old and at least 2 serum creatinine (Cr) measurements after ART initiation. Cr and urine examination were performed every 6-12 months. PRD was defined as having ≥2 measurements of low estimated glomerular filtration rate (eGFR); either <60 mL/min/1.73 m2 or elevated Cr for age and eGFR 60-89 mL/min/1.73 m2, or proteinuria (dipstick proteinuria ≥1+). Factors associated with PRD were analyzed using a multivariate logistic regression analysis., Results: This study included 255 PHAs with median (interquartile range) age of 16.7 (14.5-18.8) and ART duration of 10.3 (7.1-12.4) years. Fifty-six percentage used boosted protease inhibitor (bPI)-based regimens, and 63% used tenofovir disoproxil fumarate (TDF). The overall PRD prevalence was 14.1% [95% confidence interval (CI): 10.1-19.0]; low eGFR 6.7%, proteinuria 3.5% and both 3.9%. Among 109 users of TDF with bPI, 22.9% had PRD and 2.8% discontinued/adjusted dosing of TDF because of nephrotoxicity. Factors associated with PRD were age 10-15 years old (adjusted odd ratio (aOR): 10.1, 95% CI: 4.1-25.2), male (aOR: 3.2, 95% CI: 1.4-7.7), CD4 nadir <150 cells/mm (aOR: 2.6, 95% CI: 1.1-6.1) and use of TDF with bPI (aOR: 9.6, 95% CI: 3.2-28.9)., Conclusions: PRD is common among PHAs. Almost one-fifth of adolescents using TDF with bPI had PRD. These adolescents should be a priority group for renal monitoring.

Background: Efficacy and safety data of third-line antiretroviral (ARV) regimens in adolescents are limited., Methodology: This study enrolled HIV-infected Thais who were treated with third-line regimens consisting of darunavir/ritonavir (DRV/r), etravirine (ETR), tipranavir/ritonavir or raltegravir., Results: Fifty-four adolescents 2-17 years of age were enrolled from 8 sites and followed for 48 weeks. Reasons for switch were second-line failure (n = 44) and toxicity to second-line regimens (n = 10). At switching to third-line ARV, the median age (interquartile range) was 14.3 (12.4-15.4) years. Genotypes at time of second-line failure (n = 44) were M184V (77%), ≥4 thymidine analogue mutations (25%), non-nucleoside reverse transcriptase inhibitor-resistant associated mutation (RAM) (80%), ETR-RAM score ≥4 (14%), any lopinavir-RAM (59%) and ≥1 major DRV-RAM (41%). The third-line regimens had a median of 4 (min-max, 4-6) drugs and included ETR/DRV/r (43%), DRV/r (33%), ETR (17%), tipranavir/ritonavir (2%) or raltegravir/DRV/r/ (4%). The median CD4 (interquartile range) increased from 16% (12-21) at third-line switch to 21% (18-25) and 410 (172-682) to 607 (428-742) cells/mm at 48 weeks (P < 0.001). HIV RNA declined from 3.9 (2.9-4.9) to 1.6 (1.6-3.0) log10 copies/mL (P < 0.001) and 33/50 (66%) had levels <50 copies/mL at 48 weeks. Seventeen (31%) had HIV-RNA ≥1000 copies/mL; about half due to poor adherence; genotyping in 13 of these adolescents revealed ETR-RAM score ≥4 in 2 (15%) and ≥1 major DRV-RAM in 7 (54%)., Conclusions: Third-line ARV therapy was well tolerated and resulted in virologic suppression in 70% of adolescents at 1 year. Poor adherence and limited ARV options are major problems in the long-term management of adolescents with HIV.