466. Persistence of HIV Drug Resistance among South African Children Exposed to Nevirapine Prophylaxis for prevention of Mother-to-Child-Transmission (pMTCT)
Session: Poster Abstract Session: Pediatric HIV
Thursday, October 8, 2015
Room: Poster Hall
Background:

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.

Methods:

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.

Results:

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).

Conclusion:

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.

Ruth Kanthula, MD, MPH1,2, Ingrid Beck, MS2, Gisela Van Dyk, M.S.3, Rachel Silverman, M.S.4, Scott Olson, MD1,2, Christen Salyer, B.S.2, Sharon Cassol, PhD3, Theresa Rossouw, MBChB, MPhil, MPH, PhD3 and Lisa Frenkel, MD, FIDSA1,2, (1)Pediatric Infectious Diseases, University of Washington, Seattle, WA, (2)Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, (3)Immunology, University of Pretoria, Pretoria, South Africa, (4)Epidemiology, University of Washington, Seattle, WA

Disclosures:

R. Kanthula, None

I. Beck, None

G. Van Dyk, None

R. Silverman, None

S. Olson, None

C. Salyer, None

S. Cassol, None

T. Rossouw, None

L. Frenkel, None

See more of: Pediatric HIV
See more of: Poster Abstract Session
Previous Abstract | Next Abstract >>

Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 7th with the exception of research findings presented at the IDWeek press conferences.