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

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

Author Information

aCenter for AIDS Research Uganda Laboratories, Joint Clinical Research Centre

bTREAT, Joint Clinical Research Centre, Kampala, Uganda

cDivision of Infectious Disease, Department of Medicine

dDepartment of Mathematics, Case Western Reserve University, Cleveland, Ohio, USA.

*Fred Kyeyune and Immaculate Nankya contributed equally to the writing of this article.

Correspondence to Eric J. Arts, PhD, 10900 Euclid Avenue, BRB 1034, Cleveland, OH 44106, USA. Fax: +216 368 2034; e-mail: eja3@case.edu

Received 14 December, 2012

Revised 7 March, 2013

Accepted 8 March, 2013

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© 2013 Lippincott Williams & Wilkins, Inc.