Quantitative Analysis of HIV-1 Variants With the K103N Resistance Mutation After Single-Dose Nevirapine in Women With HIV-1 Subtypes A, C, and D

• DOI: 10.1097/01.qai.0000221686.67810.20
• Publication Date: 2006-06-13T10:27:52Z
• Authors: Tamara S. Flys; Shu Chen; Dana C. Jones; Donald R. Hoover; Jessica D. Church; Susan A. Fiscus; Anthony Mwatha; Laura A. Guay; Francis Mmiro; Philippa Musoke; Newton Kumwenda; Taha E. Taha; J. Brooks Jackson; Susan H. Eshleman
• Keywords: Malawi; Genotype; Anti-HIV Agents; Statistics as Topic; Mutation, Missense; HIV Infections; Infectious Disease Transmission, Vertical; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; Amino Acid Substitution; Pregnancy; Drug Resistance, Viral; HIV-1; Humans; Point Mutation; Female; Uganda; Nevirapine; Pregnancy Complications, Infectious

We used a sensitive point mutation assay, LigAmp, to detect and quantify K103N-containing variants in African women who received single-dose nevirapine (NVP) to prevent mother-to-child HIV-1 transmission.Plasma for testing was collected 6 to 8 weeks postpartum from 301 women (144 subtype A, 63 subtype C, and 94 subtype D).The portion of women with 0.5% or more K103N-containing variants was lowest for subtype A (60/144, 41.7%) and highest for subtype C (44/63, 69.8%; P < 0.0001). K103N was rarely detected in pre-NVP samples. In a multivariate model, K103N detection was associated with HIV-1 subtype (C > A), after adjusting for log10 delivery viral load, the number of days between NVP dosing and sample collection, age, and parity. Among women with K103N detected: (1) the median %K103N was lower for subtype A (2.2%) than C (11.7%, P = 0.0001) or D (5.5%, P = 0.04), and (2) in a multivariate linear model, higher log10 (%K103N) was associated with HIV subtype (C > A, P = 0.0001; D > A, P = 0.01; and C vs D, no difference), but not other factors.After administration of single-dose NVP, K103N was detected more frequently and at higher levels in women with subtypes C and D than A. Further studies are needed to evaluate the clinical significance of NVP-resistant variants in this setting.