Selection and persistence of viral resistance in HIV-infected children after exposure to single-dose nevirapine.
BACKGROUND
Single-dose nevirapine (sd-NVP) is the mainstay of prevention of mother-to-child transmission programs in developing countries. Exposure to sd-NVP selects for resistance mutations, however. We longitudinally assessed these mutations in HIV-1-infected infants from Soweto and Durban, South Africa.


METHODS
We prospectively followed 465 infants who received sd-NVP after enrolling their mothers when pregnant. If HIV infected, their virus was genotyped, using the ViroSeq HIV-1 Genotyping System, to detect resistant mutations. Those with resistance were genotyped at 6 months and then every 6 months out to 18 months if resistance was detected at the previous visit.


RESULTS
Of 53 HIV-infected infants, 24 (45.3%) had detectable resistance at their first visit, when the most frequent mutations were Y181C (75%), K103N (25%), and Y188C (12%). Of those whose visit was before 12 weeks of age, 2 of 42 infants shared identical resistance mutations with their mothers. By 18 months of age, 11 of 24 infants with resistance had died and 1 still had the Y181C mutation.


CONCLUSIONS
Resistant mutations were selected in half of the infants exposed to sd-NVP, but fewer were detected over time and, unlike the case in their mothers, Y181C dominated initially and persists. Transient resistance mutations may have a negative impact on highly active antiretroviral therapy in infants and children.
Martinson
Neil A
NA
Johns Hopkins University Center for Tuberculosis Research, Baltimore, MD, USA. martinson@hivsa.com
Morris
Lynn
L
Gray
Glenda
G
Moodley
Daya
D
Pillay
Visva
V
Cohen
Sarah
S
Dhlamini
Puleng
P
Puren
Adrian
A
Bhayroo
Schene
S
Steyn
Jan
J
McIntyre
James A
JA
D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D006678:HIV / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D015658:HIV Infections / Q000188:drug therapy* / Q000517:prevention & control / Q000635:transmission / Q000821:virology*; D006801:Humans; D007223:Infant; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D008137:Longitudinal Studies; D009154:Mutation; D019829:Nevirapine / Q000008:administration & dosage / Q000627:therapeutic use*; D010802:Phylogeny; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy / Q000821:virology; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D013019:South Africa
D019380:Anti-HIV Agents; D019829:Nevirapine