Children who become HIV-infected despite nevirapine (NVP) prophylaxis to pMTCT often have drug-resistant viruses that can compromise future antiretroviral therapy (ART). We studied HIV-infected, NVP-exposed children to determine the persistence of NVP resistance and its correlation with duration of exposure to NVP prophylaxis.
A prospective observational study enrolled HIV infected children with previous NVP exposure in Pretoria, South Africa. Dried blood spots were collected at enrollment and during monthly follow-up visits. Amplifiable HIV templates were quantified by polymerase chain reaction (PCR) of gag, and ~150 templates were submitted to nested HIV pol PCR. NVP-resistance was assessed by an oligonucleotide ligation assay that quantified the proportion of mutant and wild-type viral templates at four codons in reverse transcriptase with a sensitivity ≥2% mutant.
A total of 88 HIV-infected children enrolled in the study from 2010-2013 at a median age of 7.5 months (range: 1-59) and were followed for a median of 13 months (range: 2-26). Children received single-dose (sd)-NVP at birth (n=40) or NVP prophylaxis (n=48) for a median of 6 weeks (range: 1-24). At study enrollment, NVP-resistance was detected in 52% of children (Y181C (31%), K103N (20%), G190A (12%) and V106M (10%)). Children with resistance had a median mutant load of 96% (range: 3-100), were younger (median age 4.5 (range: 1-20) vs. 13.5 months (range: 1-59); P<0.0001), and a greater proportion tended to have received extended NVP prophylaxis vs. sdNVP (60% (29/48) vs. 43% (17/40); P=0.133). Among the children with resistance at enrollment, 59% were followed longitudinally for a median of 13 months (range: 9-26). Their mutant load was 98% (range: 30-100) at a median age of 4.5 months (range 1-26).
Children infected with HIV despite NVP prophylaxis, often have HIV populations consisting primarily of NVP-resistant viruses, suggesting maternal transmission of resistant variants or NVP-selection at the time the HIV reservoir was established. The persistence of high mutant loads well beyond infancy, suggests drug resistance testing is relevant in NVP-exposed children prior to non-nucleoside reverse transcriptase inhibitor-ART.
G. Van Dyk, None
R. Silverman, None
S. Olson, None
C. Salyer, None
S. Cassol, None
T. Rossouw, None
L. Frenkel, None