Nevirapine-associated hepatotoxicity and rash among HIV-infected pregnant women in Kenya.

BACKGROUND: Few studies have evaluated the risk of nevirapine (NVP)-associated hepatotoxicity among HIV-infected pregnant women with a CD4 count ≥250 cells/mm(3). METHODS: We enrolled HIV-infected pregnant Kenyan women who initiated triple antiretroviral therapy (ART) at 34 weeks gestation. We compared the rates of severe hepatotoxicity (grades 3-4 hepatotoxicity) and rash-associated hepatotoxicity (rash with ≥grade 2 hepatotoxicity) with NVP and nelfinavir (NFV), respectively. RESULTS: We initiated triple ART in 522 pregnant women; severe hepatotoxicity and rash-associated hepatotoxicity occurred in 14 (3%) and 9 (2%) women, respectively. Women who initiated NVP had higher rates of severe hepatotoxicity (5% vs 1%; P = .03) and rash-associated hepatotoxicity (4% vs 0%; P = .003) when compared with NFV. Among women who initiated NVP (n = 254), a baseline CD4 count ≥250 cells/mm(3) was not associated with severe hepatotoxicity (5% vs 3%; P = .52) or rash-associated hepatotoxicity (4% vs 3%; P = .69). CONCLUSION: Nevirapine use but not CD4 count ≥250 cells/mm(3) was associated with hepatotoxicity.

Nelfinavir and its active metabolite, hydroxy-t-butylamidenelfinavir (M8), are transferred in small quantities to breast milk and do not reach biologically significant concentrations in breast-feeding infants whose mothers are taking nelfinavir.

Antiretroviral drugs cross from maternal plasma to breast milk and from breast milk to the infant in different concentrations. We measured concentrations of nelfinavir and its active metabolite (M8) in maternal plasma and breast milk from women and in dried blood spots collected from their infants at delivery and postnatal weeks 2, 6, 14, and 24 in the Kisumu Breastfeeding Study, Kisumu, Kenya. Nelfinavir-based antiretroviral regimens given to mothers as prevention of mother-to-child HIV transmission (PMTCT) do not expose the breast-feeding infant to biologically significant concentrations of nelfinavir or M8.

Neutropenia in HIV-Infected Kenyan Women Receiving Triple Antiretroviral Prophylaxis to Prevent Mother-to-Child HIV Transmission Is Not Associated with Serious Clinical Sequelae.

BACKGROUND: Absolute neutrophil counts (ANCs) are lower in East African adults. To assess the impact of lower ANCs, we reviewed data from HIV-infected Kenyan women receiving antiretroviral therapy antepartum and postpartum. METHODS: The Kisumu Breastfeeding Study (KiBS) participants received an antiretroviral regimen from 34 weeks' gestation through 6 months postpartum. Measured ANCs and subsequent illnesses were reviewed. Adverse events (AEs) potentially attributable to neutropenia were identified, and ANCs were graded using the 2004 Division of AIDS table for Grading the Severity of AEs. RESULTS: Among 478 women with ≥1 postpartum ANC measured, 298 (62.1%) women met criteria for an AE (<1.3 × 10(9) cells/L). Of those, 38 (12.5%) women experienced a nonlife-threatening illness potentially attributable to neutropenia. CONCLUSION: More than half of KiBS women met criteria for neutropenia. The mild clinical experience of most participants with low ANCs supports that these values might be typical for this population and may not result in adverse clinical sequelae.