Minor Drug-Resistant HIV Type-1 Variants in Breast Milk and Plasma of HIV Type-1-Infected Ugandan Women after Nevirapine Single-Dose Prophylaxis

<jats:sec><jats:title>Background</jats:title><jats:p> Nevirapine single-dose (NVP-SD) reduces mother-to-child transmission of HIV type-1 (HIV-1), but frequently induces resistance mutations in the HIV-1 genome. Little is known about drug-resistant HIV-1 variants in the breast milk of women who have taken NVP-SD. </jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p> Blood and breast milk samples of 39 HIV-1-infected Ugandan women were taken 6–12 weeks after NVP-SD intake. Samples were analysed by population sequencing and allele-specific real-time PCR (AS-PCR) with detection limits for NVP-resistant HIV-1 variants (K103N and Y181C) of &lt;1% of the total viral population. </jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p> AS-PCR results for both plasma and breast milk were obtained for 19 women who constituted the final study group (HIV-1 subtype frequencies were A1 n=11, D n=5, G n=2 and C n=1). A total of 7 (37%) and 10 (53%) women carried NVP-resistant virus in breast milk and plasma, respectively. Overall, 71% (5/7) women with NVP-resistant HIV-1 in breast milk displayed &gt;1 drug-resistant variant. Resistance in breast milk was higher at week 6 (6/13 samples [46%]) compared with week 12 (1/6 samples [17%]). In total, 10 drug-resistant populations harbouring the K103N and/or Y181C mutation were detected in the 19 breast milk samples; 7 (70%) were caused by resistant minorities (&lt;5% of the total HIV-1 population). In the four women with drug-resistant virus in both plasma and breast milk, the mutation patterns differed between the two compartments. </jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p> Minor populations of drug-resistant HIV-1 were frequently found in breast milk of Ugandan women after exposure to NVP-SD. Further studies need to explore the role of minor drug-resistant variants in the postnatal transmission of (resistant) HIV-1. </jats:p></jats:sec>