Background:  HIV-1 infected children with perinatal exposure to single dose nevirapine (SDN) have been observed to have virologic failure when initiated on non-nucleoside reverse transcriptase inhibitor (NNRTI) based HAART, probably because the exposure predisposes them to developing NNRTI resistance mutations. We investigated the Drug Resistance Mutations (DRM) in HIV-1 infected SDN exposed children with virologic failure following initiation on NNRTI based HAART.

Methods:  In this study, 116 HIV infected children below 5 years of age at HAART initiation were recruited into a cohort at Joint Clinical Research Center (JCRC) in Uganda. Forty-one children (63.4% girls, median age at HAART initiation 6 months) had prior exposure to SDN. We studied the NNRTI and nucleoside reverse transcriptase inhibitor (NRTI) genotypic resistance profiles of 20 children (15 exposed and 5 unexposed to SDN) that had virologic failure at week 24 and/or at week48 following initiation of NNRTI-based HAART. The resistance sequencing was done using in house primers and edited using BioEdit Sequence Alignment Editor and analyzed using the HIV drug resistance database of Stanford University.

Results:  Virologic failure was in 17/26 (65.4%) SDN exposed compared to 19/52 (36.5%) unexposed (P =0.0127); and 18/29 (62.1%) SDN exposed compared to 17/53 (32.1%) unexposed children (P =0.0086) at weeks 24 and 48, respectively. In the exposed the commonest NNRTI DRM were: Y181C (4), G190AG (4), K103N (3), V108IV (3), K103R (2); others were: Y181V, M230L, V106A, P225ST, F227FL, A98G and K101E. The commonest NRTI DRM in the SDN exposed were: M184V (10), D67N (4), K70R (4), T219E (2), K219Q (2), E44D (2), T215F (2), T215IT (2); others were: K65R, K219R, T215FY, T215Y, A62V, T69N, V75I, M41L and V118I. Less diversity was observed in the 5 unexposed children with the commonest NNRTI DRM being K103N (4); the others were: K103RS, K238N, G190AG and M230L, and the commonest NRTI DRM was M184V (5), others being: K70R, D67N and L74V. 12 and 8 children had HIV-1 subtypes D and A, respectively. 

Conclusion:  HIV infected children with virologic failure on NNRTI based HAART and prior perinatal exposure to SDN have multiple NNRTI drug resistance mutations commonly Y181C, G190AG, K103N, V108IV as well as multiple NRTI drug resistance mutations commonly M184V, D67N and K70R. Fewer mutations were observed in the children with no prior SDN exposure, making the exposed with virologic failure more likely to have multiple drug resistance.