Nevirapine resistance by timing of HIV type 1 infection in infants treated with single-dose nevirapine.
BACKGROUND
In women, single-dose nevirapine for prophylaxis against mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) selects for nevirapine-resistant HIV-1, which subsequently decays rapidly. We hypothesized that the selection, acquisition, and decay of nevirapine-resistant HIV-1 differs in infants, varying by the timing of HIV-1 infection.


METHODS
We conducted a prospective, observational study of 740 Mozambican infants receiving single-dose nevirapine prophylaxis and determined the timing of infection and concentrations of nevirapine-resistant HIV-1 over time.


RESULTS
Infants with established in utero infection had a high rate (87.0%) of selection of nevirapine-resistant HIV-1 mutants, which rapidly decayed to undetectable levels. The few without nevirapine resistance received zidovudine with single-dose nevirapine and/or their mothers took alternative antiretroviral drugs. Infants with acute in utero infection had a lower rate of nevirapine-resistant HIV-1 (33.3%; P = .006, compared with established in utero infection), but mutants persisted over time. Infants with peripartum infection also had a lower rate of nevirapine-resistant HIV-1 (38.1%; P = .001, compared with established in utero infection) but often acquired 100% mutant virus that persisted over time (P = .017, compared with established in utero infection).


CONCLUSIONS
The detection and persistence of nevirapine-resistant HIV-1 in infants after single-dose nevirapine therapy vary by the timing of infection and the antiretroviral regimen. In infants with persistent high-level nevirapine-resistant HIV-1, nevirapine-based antiretroviral therapy is unlikely to ever be efficacious because of concentrations in long-lived viral reservoirs. However, the absence or decay of nevirapine-resistant HIV-1 in many infants suggests that nevirapine antiretroviral therapy may be effective if testing can identify these individuals.
Micek
Mark A
MA
Department of Global Health, University of Washington, Seattle, Washington, USA.
Blanco
Ana Judith
AJ
Beck
Ingrid A
IA
Dross
Sandra
S
Matunha
Laurinda
L
Montoya
Pablo
P
Seidel
Kristy
K
Gantt
Soren
S
Matediane
Eduardo
E
Jamisse
Lilia
L
Gloyd
Stephen
S
Frenkel
Lisa M
LM
D018890:Chemoprevention / Q000379:methods*; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000175:diagnosis* / Q000517:prevention & control* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D008297:Male; D009073:Mozambique; D019829:Nevirapine / Q000008:administration & dosage*; D011446:Prospective Studies; D013997:Time Factors
D019829:Nevirapine
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