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.
BACKGROUND
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.


METHODS
Plasma for testing was collected 6 to 8 weeks postpartum from 301 women (144 subtype A, 63 subtype C, and 94 subtype D).


RESULTS
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.


CONCLUSIONS
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.
Flys
Tamara S
TS
Department of Pathology, The Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
Chen
Shu
S
Jones
Dana C
DC
Hoover
Donald R
DR
Church
Jessica D
JD
Fiscus
Susan A
SA
Mwatha
Anthony
A
Guay
Laura A
LA
Mmiro
Francis
F
Musoke
Philippa
P
Kumwenda
Newton
N
Taha
Taha E
TE
Jackson
J Brooks
JB
Eshleman
Susan H
SH
D019943:Amino Acid Substitution; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000635:transmission / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D008295:Malawi; D020125:Mutation, Missense; D019829:Nevirapine / Q000494:pharmacology* / Q000627:therapeutic use; D017354:Point Mutation; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy / Q000821:virology*; D013223:Statistics as Topic; D014454:Uganda
D019380:Anti-HIV Agents; D019829:Nevirapine