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AIDS:
doi: 10.1097/QAD.0b013e3283610ec7
Clinical Science

Treatment failure and drug resistance is more frequent in HIV-1 subtype D versus subtype A-infected Ugandans over a 10-year study period

Kyeyune, Freda,*; Nankya, Immaculatea,b,c,*; Metha, Samara,b; Akao, Julieta,b; Ndashimye, Emmanuela; Tebit, Denis M.c; Rodriguez, Benignoc; Kityo, Cissya,b; Salata, Robert A.c; Mugyenyi, Petera,b; Arts, Eric J.a,c; the JCRC Drug Resistance Working Group

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Abstract

Objectives: To determine the impact of HIV-1 subtype on treatment outcomes and the emergence of drug resistance in the resource limited setting of Kampala, Uganda.

Design: The Joint Clinical Research Centre (JCRC) in Kampala, Uganda has provided over 2000 drug-resistant genotypes (DRGs) over the past 10 years as standard of care for patients failing therapy and 1403 from treatment-naive and experienced patients over the past 10 years have been analyzed for this study.

Method: Viral loads, CD4 cell count, treatment histories and other relevant clinical data was compared with the infecting HIV-1 subtype and DRGs of Ugandan patients failing treatment.

Results: Patients failing HAART with DRGs (n = 937) were more frequently infected with subtype D than expected on the basis of the subtype distribution in the treatment-naive population (n = 655) in Kampala (P < 0.001). Higher proportions of treatment failures among subtype D-infected patients were driven by resistance to nucleoside reverse transcriptase inhibitors (NRTI) (P < 0.0002) more than to non-NRTIs (P > 0.04) or protease inhibitors.

Conclusion: Higher rates of treatment failure among subtype D as compared with subtype A-infected Ugandans was analogous to the faster disease progression in subtype D-infected patients. The mechanism(s) by which drug resistance may emerge faster in subtype D HIV-1 may relate to higher replicative fitness and increased propensity for a CXCR4 tropism.

© 2013 Lippincott Williams & Wilkins, Inc.

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