Minor drug-resistant human immunodeficiency virus (HIV)-1 variants in the cellular DNA of Tanzanian women following triple antiretroviral regimen to prevent vertical transmission

Antenatal zidovudine (AZT), intrapartal nevirapine (NVP) and postpartal lamivudine (3TC)/AZT to prevent mother-to-child transmission of human immunodeficiency virus (HIV)-1 as recommended in 2006 World Health Organization (WHO) guidelines has shown to select HIV-resistant plasma virus in Tanzanian women. During viral replication, HIV integrates into the cellular host genome where resistant strains may remain archived. This study analyzed the dimension of integration of drug-resistant HIV-strains into the host cells as provirus by analyzing corresponding peripheral blood mononuclear cells (PBMCs) for key resistance mutations selected by AZT/NVP/3TC, applying highly-sensitive allele-specific polymerase chain reaction (PCR). HIV-resistance was detected in PBMC-DNA of 10 (28%) and in plasma virus of 15 of 36 women (42%). Most resistance mutations were selected by AZT in comparable proportions in PBMCs (25%) and in plasma virus (22%). In conclusion, antenatal AZT may select for AZT-resistance potentially persisting as provirus, and therefore is likely to negatively impact future treatment options.   Key words: Tanzania, prevention of mother-to-child transmission of human immunodeficiency virus (HIV)-1, triple prophylaxis, HIV-1 drug resistance, peripheral blood mononuclear cells (PBMCs), proviral DNA, minor variants, allele-specific polymerase chain reaction (PCR).