92
Nevirapine-resistant HIV-1 among Mozambican Infants Infected in Utero vs Intra-partum or Early Postpartum
M Micek1,2, M Micek1,2, A Blanco1,2, A Blanco1,2, E Matediane3, L Matunha2, I Beck4, S Dross4, P Montoya1,2, P Montoya1,2, L Jamisse5, S Gloyd1,2, S Gloyd1,2, and Lisa Frenkel*1
1Univ of Washington, Seattle, US; 2Hlth Alliance Intl, Seattle, WA, US; 3Mozambique Ministry of Hlth, Biera; 4Children's Hosp, Seattle, WA, US; and 5Mozambique Ministry of Hlth, Maputo
Background: Nevirapine (NVP) -resistant
HIV-1 has been detected in 15 to 60% of infected infants following single-dose NVP
given to mothers and their newborns to reduce mother-to-child HIV-1
transmission (MTCT). We hypothesized that the selection and persistence of
NVP-resistant virus will differ in infants infected in utero (defined as first HIV-1 DNA polymerase
chain reaction [PCR] [+] at birth) compared with those infected intra-partum or
early postpartum (defined as first HIV-1 DNA PCR (+) at 2 to 8 weeks old).
Methods: An observational cohort study is ongoing to
characterize the selection of NVP-resistant HIV-1 and its persistence in
infants who received single-dose NVP as recommended by the Mozambique Ministry
of Health in Beira, Mozambique. Newborns were recruited through mothers before
or at the time of birth. Whole blood collected on FTATM filter-paper
from all infants at birth, 2, 4, 6, and 8 weeks of age was assessed for HIV-1
infection by DNA PCR of HIV-1 pol. NVP-mutants (K103N, Y181C, and G190A) were detected in
the HIV-1 DNA pol
amplicons by an oligonucleotide
ligation assay (OLA) that can reliably detect 5%
mutant.
Results: NVP-resistance data are available for 18
infants, 12 infected in utero and 6 infected intra-partum or early postpartum.
Of infants infected in utero 12 of 12 (100%) had resistance mutations
detected, including Y181C (10 infants), K103N (9 infants), and G190A (3
infants). The prevalence of mutants appeared greatest when infants were 4 weeks
old and persisted through 8 weeks of age in 10 of 12 infants. The selection of
NVP-resistant mutants appeared lower among infants infected between 0 and 8
weeks postpartum with a single mutant genotype detected in 2 of 6 (33%) infants
(Y181C and G190A).
Conclusions: The selection of common NVP-resistance
mutations was high in Mozambican infants receiving single-dose NVP and infected
with HIV-1 in utero
compared to infants infected intra-partum or early postpartum. While most
mutants were detected through 8 weeks of age, the persistence and long-term
consequences of these HIV-1 resistance mutations remains unknown. Further
analyses in this study will focus on the persistence of mutants, as gauged by
sensitive assays, in infants infected in utero versus intra-partum or early postpartum.
|
