Transmission of nevirapine-resistant HIV type 1 via breast milk to infants after single-dose nevirapine in Beira, Mozambique

Abstract

Acquisition of nevirapine (NVP)-resistant human immunodeficiency virus type 1 (HIV-1) by breast-feeding infants after receipt of single-dose NVP to prevent mother-to-child transmission is not well defined. A prospective observational study of 307 infants evaluated the rate of breast milk transmission of NVP-resistant HIV and the concentrations of mutants over time. NVP resistance was detected in 9 of 24 infants (37.5%; 95% confidence interval, 18.8%-59.4%) infected via breast milk. Eight had a pure mutant HIV population at the time infection was first detected, and majority mutant populations persisted in all 6 infants with follow-up specimens. Infection of breast-feeding infants with NVP-resistant HIV resulted in mutants persisting as the dominant virus, which may indefinitely compromise treatment with NVP-based antiretroviral regimens.

Keywords: HIV-1; drug-resistance; mother-to-child transmission; nevirapine; zidovudine.

Figure 1.

Timing of the diagnosis of human immunodeficiency virus type 1 (HIV-1) infection and the detection and concentration of NVP-resistant virus among infants infected through breast milk following single-dose NVP dosing of mothers and infants. Infants’ specimens that were positive for HIV DNA by polymerase chain reaction were tested for nevirapine resistance, using an oligonucleotide ligation assay (OLA) for detection of K103N, V106M, Y181C, and G190A; the OLA had a sensitivity to detect mutants in 2% of the population. Transmission via breast milk was considered “definite” for infants with an HIV DNA–negative PCR result at 2 weeks of age and a positive test result at ≥1 month of age. Transmission was considered “possible” for infants who tested negative for HIV DNA by PCR at birth, had no specimens obtained at 2 weeks of age available for testing, and tested positive for HIV DNA by PCR at ≥4 weeks of age. Numbers in boxes represent the proportion of the HIV population with NVP-resistant DNA. Resistance detected by OLA is shown, and additional mutations detected by consensus sequencing are as follows: ^aM41L, ^bM184V (maternal ART started at about 7 weeks after delivery, and ^cY188C/Y (detected at 7 months). Abbreviation: WT, wild-type virus.