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Treatment Failure and Drug Resistance is More Frequent in HIV-1 Subtype D versus subtype A-infected Ugandans Over a 10-year Study Period

Publication year: 
2013
Author (s): 
Kyeyune, Fred [et al.]
Publication details: 
London, Lippincott Williams & Wilkins, 2013
Publication in: 
AIDS 2013, 27: pp. 1899–1909
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 (n¼937) were more frequently infected
with subtype D than expected on the basis of the subtype distribution in the treatmentnaive population (n¼655) 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.