Minor resistant variants in nevirapine-exposed infants may predict virologic failure on nevirapine-containing ART.
BACKGROUND
Single-dose nevirapine (sdNVP) is widely used to prevent mother-to-child transmission (PMTCT) of HIV-1. This may result in NVP resistance in both mother and infant. The significance of low levels of NVP resistance mutations in infants treated with NVP-containing antiretroviral treatment (ART) is unknown.


OBJECTIVE
To determine the presence of pre-treatment NVP resistance in HIV-infected infants with and without prior NVP exposure.


METHODS
33 HIV-1-infected infants in a PMTCT trial received NVP-containing ART (26 infants with prior NVP exposure). Plasma and buffy coat samples obtained prior to ART initiation were evaluated for drug resistance by bulk sequencing and allele-specific PCR (ASPCR).


RESULTS
ViroSeq identified NVP resistance in 3 of 33 infants; all failed first-line therapy. Pre-ART plasma NVP resistance by ASPCR was detected in 9 of 16 children experiencing virologic failure compared to 4 of 17 children without virologic failure (risk ratio 2.4, CI 0.94-7.8, p=0.08). Proviral resistance was not associated with virologic failure (risk ratio 1.2, CI 0.8-2.0, p=0.40). In the nevirapine-exposed infants, those who started ART before 7 months had higher risk of virologic failure (RR 2.3, CI 0.96-9.2, p=0.11).


CONCLUSIONS
Low level drug resistance detected in plasma after NVP exposure prior to ART initiation may be associated with virologic failure on ART, while resistance in the DNA reservoir was not predictive of treatment outcome.
MacLeod
Iain J
IJ
Department of Immunology and Infectious Diseases, Harvard School of Public Health, 651 Huntington Ave., Boston, MA 02115, United States.
Rowley
Christopher F
CF
Thior
Ibou
I
Wester
Carolyn
C
Makhema
Joseph
J
Essex
Max
M
Lockman
Shahin
S
D019943:Amino Acid Substitution / Q000235:genetics; D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D004279:DNA, Viral / Q000235:genetics; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D020125:Mutation, Missense; D019829:Nevirapine / Q000494:pharmacology / Q000627:therapeutic use*; D011247:Pregnancy; D012367:RNA, Viral / Q000235:genetics; D017422:Sequence Analysis, DNA; D017211:Treatment Failure
D019380:Anti-HIV Agents; D004279:DNA, Viral; D012367:RNA, Viral; D019829:Nevirapine