Development of Phenotypic and Genotypic Resistance to Antiretroviral Therapy in the UNAIDS HIV Drug Access Initiative – Uganda

Abstract

Objective: We describe phenotypic drug resistance, response to therapy, and geno-typic mutations among HIV-infected patients in Uganda taking antiretroviral medica-tions for ≥ 90 days who had a viral load ≥ 1000 copies/ml. Methods: HIV-1 group and subtype, virologic and immunologic responses to anti-retroviral therapy, phenotypic resistance to antiretroviral drugs, and associated geno-typic mutations among patients at three treatment centers in Uganda between June 1999 and August 2000 were assessed. Therapy was two nucleoside reverse tran-scriptase inhibitors (NRTIs) or highly active antiretroviral therapy (HAART). Results: All HIV identified was HIV-1, group M, subtypes A, C, and D. Sixty-one (65%) of 94 patients with a phenotypic resistance result had evidence of phenotypic resistance including resistance to a NRTI for 51 of 92 (55%) taking NRTIs, to a non-nucleoside reverse transcriptase inhibitor (NNRTI) for nine of 16 (56%) taking NNRTIs, and to a protease inhibitor (PI) for eight of 37 (22%) taking PIs. At the time of the first specimen with resistance, the median change from baseline viral load was –0.56 log copies/ml [interquartile range (IQR), –1.47 to +0.29] and CD4+ cell count was +35 × 106 cells/l (IQR, –18 to +87). Genotypic resistance mutations, matched with phenotypic resistance assay results and drug history, were generally consistent with those seen for HIV-1, group M, subtype B infections in industrialized countries. Conclusion: Initial phenotypic resistance and corresponding genotypic mutations among patients treated in Uganda were similar to those with subtype B infections in North America and Europe. These data support policies that promote the use of HAART regimens against HIV-1, group M, non-B subtypes in a manner consistent with that used for subtype B infections.