Triple-drug antiretroviral prophylaxis of zidovudine (AZT)/lamivudine (3TC)/nevirapine (NVP) for high risk HIV-exposed neonates is recommended within the Thai national program. However, there are limited data about the safety and drug concentration achieved with this regimen initiated at birth.
Prospective cohort of infants born from HIV-infected pregnant women in 4 clinical sites in Thailand. Neonates with high risk of HIV transmission (mother has HIV RNA >50 copies/mL prior to delivery or received ART <12 weeks) received AZT and 3TC twice daily, plus NVP (4 mg/kg/dose) once daily, for 6 weeks. As a control group, neonates with standard risk of HIV transmission who received 4-weeks of AZT were also enrolled. Blood for complete blood count, aspatate transaminase (AST), alanine transaminase (ALT) were drawn at birth, aged 1, 2 and 4 month. Adverse events were graded according to DAIDS toxicity table 2014. Sparse plasma NVP concentrations were collected at week 1, 2 and 4 and assayed by a validated liquid chromatography-triple quadrupole mass spectrometry assay. Target NVP plasma trough concentration for prophylaxis was >100 ng/mL.
From October 2015 to August 2016, 94 infants were enrolled. 31 neonates received triple ARV prophylaxis and 63 infants received AZT only. Overall, median (IQR) gestational age and birth weight were 38 (37-39) weeks and 2.8 (2.5-3.2) kg, respectively. Maternal ART during pregnancy were 39 (42%) TDF/3TC/EFV, 13 (14%) AZT/3TC/LPV/r, 11 (12%) TDF/3TC/LPV/r and 28 (30%) others. Median (IQR) infant hemoglobin at week 1 and 4 were 16.3 (15.3-18.1) and 10.4 (9.3-11.7) g/dL with no significant difference between the groups. There was no difference in adverse event rates between triple and AZT prophylaxis; all grade anemia (43.6% vs 39.9%), grade 3-4 anemia (3.2% vs 3.1%), all grade neutropenia (3.2% vs 3.0%), grade 3-4 neutropenia (1.1% vs 0.3%), elevated AST (1.1% vs. 1.5%), and elevated ALT (3.2 vs. 4.0%). No infants were diagnosed HIV-infected at age 4 months. NVP concentrations were available from 18 infants: geometric mean (%CV) plasma NVP concentrations were 3075 (67), 2109 (92) and 1438 (72) ng/mL at weeks 1, 2 and 4, respectively (Figure 1). All infants maintained nevirapine concentrations >100 ng/mL during the first 4 weeks.
Triple ART infant prophylaxis with 6-weeks of AZT/3TC/NVP in high risk HIV-exposed infants appears to be safe with high NVP concentrations being rapidly achieved and maintained during the first 4 weeks of life.