Background:  Subtypes A and D are the predominant HIV-1 clades found in Uganda. There is evidence that ART developed against HIV-1 subtype B has activity against the non-B subtypes that predominate in areas of the world where other HIV clades are common. Few data comprehensively examine the relationship between viral subtype and resistance (genotype/phenotype), replication capacity, and viral tropism in individuals with non-B subtypes treated with ART. With this in mind, the objective of this study was to examine this relationship in Ugandan children failing their first ART regimen.

Methods:  A retrospective evaluation was performed on 36 children attending the Pediatric Infection Disease Clinic, Mulago Hospital, Kampala, who failed their first ART. Stored blood (–70°C), drawn at the time of ART failure, was evaluated for viral load, CD4 count, subtype, genotypic and phenotypic resistance, replication capacity, and viral tropism. Among these children, 74% received nevirapine (NVP)/stavudine (d4T) or zidovudine (AZT) -based therapy and 26% received efavirenz (EFV)/d4T or AZT-based therapy. All children received lamivudine (3TC).

Results:  Of the children, 41% were subtype A and 36% subtype D. Subtypes C and recombinant subtypes A/D, A/C, C/D were also represented. Replication capacity was greater in children failing therapy with subtype DOf all children failing therapy, 61% had a dual mixed (R5X4) tropism, 32% were R5, and 7% X4. Genotypically, all children failing therapy had M184V and NNRTI mutations (K103N, G190A, Y181C predominated). One child had a Q151M mutation at first failure. All AZT/d4T mutations were observed but M41L and L210W had a low representation in this population of children (one child had M41L and one had L210W). Phenotypic resistance mirrored the genotypic pattern, except that only one child (Q151M mutation) had phenotypic resistance to d4T.

Conclusions:  As the use of ART grows in Africa and failure of ART regimens appears more often in these resource-poor settings, it will be critical to understand the relationship between viral subtype and response to ART medications.