Slower clearance of nevirapine resistant virus in infants failing extended nevirapine prophylaxis for prevention of mother-to-child HIV transmission.
Nevirapine resistance mutations arise commonly following single or extended-dose nevirapine (ED-NVP) prophylaxis to prevent mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV), but decay within 6-12 months of single-dose exposure. Use of ED-NVP prophylaxis in infants is expected to rise, but data on decay of nevirapine resistance mutations in infants in whom ED-NVP failed remain limited. We assessed, in Ethiopian infants participating in the Six-Week Extended Nevirapine (SWEN) Trial, the prevalence and persistence of nevirapine resistance mutations at 6 and 12 months following single-dose or up to 6 weeks of ED-NVP, and correlated their presence with the timing of infection and the type of resistance mutations. Standard population genotyping followed by high-throughput cloning were done on dried blood spot samples collected during the trial. More infants who received ED-NVP had nevirapine resistance detected by standard population genotyping (high frequencies) at age 6 months compared with those who received single-dose nevirapine (SD-NVP) (58% of 24 vs. 26% of 19, respectively; p = 0.06). Moreover, 56% of ED-NVP-exposed infants with nevirapine resistance at age 6 months still had nevirapine resistance mutations present at high frequencies at age 1 year. Infants infected before 6 weeks of age who received either SD- or ED-NVP were more likely to have Y181C or K103N; these mutations were also more likely to persist at high frequencies through 1 year of age. HIV-infected infants in whom ED-NVP prophylaxis fails are likely to experience delayed clearance of nevirapine-resistant virus in the first year of life, which in turn places them at risk for early selection of multidrug-resistant HIV after initial therapy with nonnucleoside reverse transcriptase inhibitor-based regimens.
Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA. dpers@jhmi.edu
Deborah
D
Persaud
Abubaker
A
Bedri
Carrie
C
Ziemniak
Anitha
A
Moorthy
Berhanu
B
Gudetta
Aida
A
Abashawl
Yohannes
Y
Mengistu
Saad B
SB
Omer
Abdulhamid
A
Isehak
Solomon
S
Kumbi
Rahel
R
Adamu
Sileshi
S
Lulseged
Roxann
R
Ashworth
Elham
E
Hassen
Andrea
A
Ruff
D001483:Base Sequence; D001942:Breast Feeding; D002648:Child; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral; D005002:Ethiopia; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000208:ethnology / Q000517:prevention & control / Q000635:transmission / Q000821:virology; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D008297:Male; D008969:Molecular Sequence Data; D058889:Molecular Typing; D009154:Mutation; D019829:Nevirapine / Q000008:administration & dosage / Q000627:therapeutic use; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy* / Q000517:prevention & control / Q000821:virology; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D019562:Viral Load / Q000187:drug effects
D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine; D054303:HIV Reverse Transcriptase
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