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1.
J Acquir Immune Defic Syndr ; 75(5): 554-560, 2017 08 15.
Article in English | MEDLINE | ID: mdl-28489732

ABSTRACT

BACKGROUND: Nevirapine (NVP) is a key component of antiretroviral prophylaxis and treatment for neonates. We evaluated current World Health Organization (WHO) weight-band NVP prophylactic dosing recommendations and investigated optimal therapeutic NVP dosing for neonates. METHODS: The PHPT-5 study in Thailand assessed the efficacy of "Perinatal Antiretroviral Intensification" to prevent mother-to-child transmission of HIV in women with <8 weeks of antiretroviral treatment before delivery (NCT01511237). Infants received a 2-week course of zidovudine/lamivudine/NVP (NVP syrup/once daily: 2 mg/kg for 7 days; then 4 mg/kg for 7 days). Infant samples were assessed during the first 2 weeks of life. NVP population pharmacokinetics (PK) parameters were estimated using nonlinear mixed-effects models. Simulations were performed to estimate the probability of achieving target NVP trough concentrations for prophylaxis (>0.10 mg/L) and for therapeutic efficacy (>3.0 mg/L) using different infant dosing strategies. RESULTS: Sixty infants (55% male) were included. At birth, median (range) weight was 2.9 (2.3-3.6) kg. NVP concentrations were best described by a 1-compartment PK model. Infant weight and postnatal age influenced NVP PK parameters. Based on simulations for a 3-kg infant, ≥92% would have an NVP trough >0.1 mg/L after 48 hours through 2 weeks using the PHPT-5 and WHO-dosing regimens. For NVP-based therapy, a 6-mg/kg twice daily dose produced a trough >3.0 mg/L in 87% of infants at 48 hours and 80% at 2 weeks. CONCLUSION: WHO weight-band prophylactic guidelines achieved target concentrations. Starting NVP 6 mg/kg twice daily from birth is expected to achieve therapeutic concentrations during the first 2 weeks of life.


Subject(s)
Anti-HIV Agents/administration & dosage , Chemoprevention/methods , HIV Infections/drug therapy , HIV Infections/prevention & control , Infectious Disease Transmission, Vertical/prevention & control , Nevirapine/pharmacokinetics , Pregnancy Complications, Infectious , Anti-HIV Agents/pharmacokinetics , Anti-HIV Agents/therapeutic use , Breast Feeding , Clinical Protocols , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , HIV Infections/transmission , Humans , Infant, Newborn , Lamivudine/administration & dosage , Lamivudine/pharmacokinetics , Lamivudine/therapeutic use , Male , Nevirapine/administration & dosage , Nevirapine/therapeutic use , Practice Guidelines as Topic , Pregnancy , Pregnancy Complications, Infectious/virology , Thailand , World Health Organization , Zidovudine/administration & dosage , Zidovudine/pharmacokinetics , Zidovudine/therapeutic use
2.
Antivir Ther ; 21(5): 435-40, 2016.
Article in English | MEDLINE | ID: mdl-26492107

ABSTRACT

BACKGROUND: Antiretroviral (ARV) regimens used for the prevention of mother-to-child transmission of HIV have evolved over time. We evaluated the contribution of different ARV regimens on the reduction of the plasma HIV RNA viral load (VL) during pregnancy. METHODS: A total of 1,833 VL measurements from ARV-naive pregnant women participating in perinatal prevention trials in Thailand were included. Women received either zidovudine (ZDV) monotherapy, ZDV plus lopinavir/ritonavir (LPV/r), or ZDV plus lamivudine (3TC) plus LPV/r. VL time-course during pregnancy was described as a function of pretreatment VL and treatment duration using an Emax non-linear mixed-effect model. VL reduction and median time to achieve a VL<50 copies/ml were estimated for each regimen. RESULTS: Among 745 women, 279 (37%), 145 (20%) and 321 (43%) received ZDV monotherapy, ZDV+LPV/r and ZDV+3TC+LPV/r, respectively. The predicted VL reduction from baseline to delivery after a median of 10 weeks of treatment were 0.5, 2.7 and 2.9 log10 copies/ml with ZDV monotherapy, ZDV+LPV/r and ZDV+3TC+LPV/r, respectively. At delivery, 1%, 57% and 63% of women receiving ZDV monotherapy, ZDV+LPV/r or ZDV+3TC+LPV/r had a VL<50 copies/ml. The addition of 3TC to ZDV+LPV/r reduced the time to achieve a VL<50 copies/ml and the higher the pretreatment VL, the larger the effect 3TC had on reducing the time to VL<50 copies/ml. CONCLUSIONS: The addition of 3TC to ZDV+LPV/r was associated with a slight further VL reduction but the time to reach a VL<50 copies/ml was shorter. This beneficial effect of 3TC is crucial for prevention of mother-to-child transmission in women who receive ARVs late and with high pretreatment VL.


Subject(s)
Anti-HIV Agents/administration & dosage , HIV Infections/complications , HIV Infections/drug therapy , Pregnancy Complications, Infectious/drug therapy , Pregnancy Complications, Infectious/virology , Adult , Drug Therapy, Combination , Female , HIV Infections/virology , HIV-1/drug effects , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical/prevention & control , Lamivudine/administration & dosage , Lopinavir/administration & dosage , Pregnancy , Ritonavir/administration & dosage , Thailand , Viral Load/drug effects , Zidovudine/administration & dosage
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