Concentrations of tenofovir, lamivudine and efavirenz in mothers and children enrolled under the Option B-Plus approach in Malawi

Objectives: To evaluate antiretroviral drug concentrations in mothers and infants enrolled under the Option B-Plus approach for the prevention of HIV mother-to-child transmission in Malawi and to assess the maternal virological response after 1 year of treatment. Patients and methods: Forty-seven women and 25 children were studied. Mothers were administered during pregnancy a combination of tenofovir lamivudine and efavirenz and continued it during breastfeeding (up to 2 years) and thereafter. Drug concentrations were evaluated in mothers (plasma and breast milk) at 1 and 12 months post-partum and in infants (plasma) at 6 and 12 months of age. Drug concentrations were determined using an LC-MS/MS validated methodology. Results: In breast milk tenofovir concentrations were very low (breast milk/maternal plasma ratio = 0.08) while lamivudine was concentrated (breast milk/plasma ratio = 3) and efavirenz levels were 80% of those found in plasma. In infants median levels at 6 months were 24 ng/mL tenofovir 2.5 ng/mL lamivudine and 86.4 ng/mL efavirenz. At month 12 median levels were below the limit of quantification for the three drugs. No correlation was found between drug concentrations and laboratory parameters or indices of growth. HIV-RNA >1000 copies/mL was seen at month 1 in 15% of the women and at month 12 in 8.5%. Resistance was found in half of the women with detectable viral load. Conclusions: Breastfeeding infants under Option B-Plus are exposed to low concentrations of antiretroviral drugs. With this strategy mothers had a good virological response 1 year after delivery.