Abstract:
Background: Triple-drug antiretroviral prophylaxis of zidovudine (ZDV)/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.
Objectives: This study aims to evaluate the safety of this triple drug neonatal prophylaxis regimen and to describe nevirapine concentration levels during the first 4 weeks of life.
Methods: A prospective cohort of HIV-exposed infants was conducted at 5 clinical sites in Thailand. We enrolled 100 high-risk HIV-exposed neonates (maternal HIV RNA >50 copies/mL prior to delivery or received antiretroviral therapy (ART) <12 weeks) who received ZDV/ 3TC twice daily, plus NVP (4 mg/kg/dose) once daily, from birth for 6 weeks, and 100 standard-risk HIV-exposed neonates who received a 4-week regimen of ZDV. Blood tests to assess hematologic and liver toxicities were performed at birth, 1, 2 and 4 months of life. Sparse plasma NVP concentrations were collected at day 1, 2, 7, 14, and 28 and assayed by a validated liquid chromatography-mass spectrometry assay.
Results: From October 2015 to November 2017, 200 infants were enrolled. Median (IQR) gestational age and birth weight were 38 (37-39) weeks and 2,873 (2,590-3,184) g, respectively. Common maternal ART regimens were TDF/3TC or emtricitabine (58%), ZDV/3TC (32%) in combination with efavirenz (50%), ritonavir boosted protease inhibitor (31%). There was no significant difference of adverse events between triple prophylaxis and ZDV alone; percentage of anemia 69.8% vs 66.3%, p=0.46. Median (IQR) hemoglobin level among infants who received triple prophylaxis were 9.9 (9.0-11.4) g/dL, 10.1 (9.3-11.0), and 11.7 (11.0-12.3) at aged 1, 2 and 4 months, respectively, which did not significantly differ between groups. Rate of HIV transmission among definite HIV-exposed high risk infants was 1.7% (95% CI 0.3%-8.9%). NVP concentrations were available from 48 infants (135 samples); median predicted NVP Ctrough were 1.34 mg/L, 2.24, 2.78, 2.20, and 0.81 on days 1, 2, 7, 14, and 28 of life, respectively. All infants maintained NVP concentrations above the proposed prophylactic target threshold of 0.1 mg/L during the first 4 weeks.
Conclusions: Six-weeks of ZDV/3TC/NVP in HIV-exposed infants did not increase the risk of toxicity compared with an ZDV regimen. Administration of 4 mg/kg of NVP from birth provided adequate NVP concentrations for prophylaxis during the first 4 weeks of life.
