Slower clearance of nevirapine resistant virus in infants failing extended nevirapine prophylaxis for prevention of mother-to-child HIV transmission

• Published in: AIDS research and human retroviruses Vol. 27; no. 8; p. 823
• Main Authors: Persaud, Deborah, Bedri, Abubaker, Ziemniak, Carrie, Moorthy, Anitha, Gudetta, Berhanu, Abashawl, Aida, Mengistu, Yohannes, Omer, Saad B, Isehak, Abdulhamid, Kumbi, Solomon, Adamu, Rahel, Lulseged, Sileshi, Ashworth, Roxann, Hassen, Elham, Ruff, Andrea
• Format: Journal Article
• Language: English
• Published: United States 01.08.2011
• Subjects: Base Sequence; Breast Feeding; Child; Drug Administration Schedule; Drug Resistance, Viral; Ethiopia; Female; Gene Frequency; Genotype; HIV Infections - drug therapy; HIV Infections - ethnology; HIV Infections - prevention & control; HIV Infections - transmission; HIV Infections - virology; HIV Reverse Transcriptase; HIV-1 - drug effects; HIV-1 - genetics; HIV-1 - growth & development; Humans; Infant; Infant, Newborn; Infectious Disease Transmission, Vertical - prevention & control; Male; Molecular Sequence Data; Molecular Typing; Mutation; Nevirapine - administration & dosage; Nevirapine - therapeutic use; Pregnancy; Pregnancy Complications, Infectious - drug therapy; Pregnancy Complications, Infectious - prevention & control; Pregnancy Complications, Infectious - virology; Reverse Transcriptase Inhibitors - administration & dosage; Reverse Transcriptase Inhibitors - adverse effects; Reverse Transcriptase Inhibitors - therapeutic use; Viral Load - drug effects; Ethiopia
• ISSN: 1931-8405
• DOI: 10.1089/aid.2010.0346

Nevirapine resistance mutations arise commonly following single or extended-dose nevirapine (ED-NVP) prophylaxis to prevent mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV), but decay within 6-12 months of single-dose exposure. Use of ED-NVP prophylaxis in infants is expected to rise, but data on decay of nevirapine resistance mutations in infants in whom ED-NVP failed remain limited. We assessed, in Ethiopian infants participating in the Six-Week Extended Nevirapine (SWEN) Trial, the prevalence and persistence of nevirapine resistance mutations at 6 and 12 months following single-dose or up to 6 weeks of ED-NVP, and correlated their presence with the timing of infection and the type of resistance mutations. Standard population genotyping followed by high-throughput cloning were done on dried blood spot samples collected during the trial. More infants who received ED-NVP had nevirapine resistance detected by standard population genotyping (high frequencies) at age 6 months compared with those who received single-dose nevirapine (SD-NVP) (58% of 24 vs. 26% of 19, respectively; p = 0.06). Moreover, 56% of ED-NVP-exposed infants with nevirapine resistance at age 6 months still had nevirapine resistance mutations present at high frequencies at age 1 year. Infants infected before 6 weeks of age who received either SD- or ED-NVP were more likely to have Y181C or K103N; these mutations were also more likely to persist at high frequencies through 1 year of age. HIV-infected infants in whom ED-NVP prophylaxis fails are likely to experience delayed clearance of nevirapine-resistant virus in the first year of life, which in turn places them at risk for early selection of multidrug-resistant HIV after initial therapy with nonnucleoside reverse transcriptase inhibitor-based regimens.