Emergence of minor drug-resistant HIV-1 variants after triple antiretroviral prophylaxis for prevention of vertical HIV-1 transmission

• Published in: PloS one 2012-02, Vol.7 (2), p.e32055
• Main Authors: Hauser, Andrea, Sewangi, Julius, Mbezi, Paulina, Dugange, Festo, Lau, Inga, Ziske, Judith, Theuring, Stefanie, Kuecherer, Claudia, Harms, Gundel, Kunz, Andrea
• Format: Article
• Language: English
• Subjects: Acquired immune deficiency syndrome; Adult; AIDS; Alleles; Analysis; Analytical methods; Anti-Retroviral Agents - pharmacology; Antiretroviral agents; Antiretroviral drugs; Biology; Breast feeding; Detection limits; Disease resistance; Disease transmission; Drug resistance; Drug Resistance, Viral; Drug therapy; Emergence; Female; Genetic Variation; Guidelines; Highly active antiretroviral therapy; HIV; HIV Infections - prevention & control; HIV Infections - transmission; HIV tests; HIV-1 - drug effects; HIV-1 - genetics; Human immunodeficiency virus; Humans; Impact resistance; Infants; Infectious Disease Transmission, Vertical - prevention & control; Labor; Lamivudine; Lamivudine - administration & dosage; Medicine; Microbial drug resistance; Mutation; Nevirapine; Nevirapine - administration & dosage; Oligonucleotides - genetics; Polymerase Chain Reaction - methods; Postpartum; Pregnancy; Pregnancy Complications, Infectious; Pregnant women; Prevention; Prophylaxis; Protease inhibitors; Tanzania; Viruses; Womens health; Zidovudine; Zidovudine - administration & dosage
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0032055

WHO-guidelines for prevention of mother-to-child transmission of HIV-1 in resource-limited settings recommend complex maternal antiretroviral prophylaxis comprising antenatal zidovudine (AZT), nevirapine single-dose (NVP-SD) at labor onset and AZT/lamivudine (3TC) during labor and one week postpartum. Data on resistance development selected by this regimen is not available. We therefore analyzed the emergence of minor drug-resistant HIV-1 variants in Tanzanian women following complex prophylaxis. 1395 pregnant women were tested for HIV-1 at Kyela District Hospital, Tanzania. 87/202 HIV-positive women started complex prophylaxis. Blood samples were collected before start of prophylaxis, at birth and 1-2, 4-6 and 12-16 weeks postpartum. Allele-specific real-time PCR assays specific for HIV-1 subtypes A, C and D were developed and applied on samples of mothers and their vertically infected infants to quantify key resistance mutations of AZT (K70R/T215Y/T215F), NVP (K103N/Y181C) and 3TC (M184V) at detection limits of