Background: Few reports have described drug resistance patterns in areas where HIV subtype C is predominant, and there has been no such report in Zambia. We evaluated resistance patterns in patients failing first-line regimens in Zambia and its potential impact on second-line therapy options.
Methodology: A retrospective, descriptive analysis of available genotypes from three urban ART clinics in Lusaka was performed for patients failing first-line ART before December 2010.
Results: 126 genotypes were analyzed: 19% were wild type, and 81% contained at least one major mutation. The most frequently observed mutations were: M184V (83.3%), NNRTI mutations (K103N and Y181C/I, 76.4%), and TAMs (59%); 43% had >=2TAMS. K65R was found in 2 patients failing TDF, one failing d4T, and one failing AZT. 85% had both NRTI and NNRTI mutations, and 38% were predicted to be resistant to ETV. Subtype C/C was predominant (95.2%); others identified were B/C (2.4%), D/C (1.6%), and B/B (0.8%). 92% of analyzed genotypes were from pediatric patients, and 92% were on thymidine analog based regimens.
Conclusion: In this predominately pediatric population with HIV subtype C, resistance patterns after first-line failure were similar to those described with subtype B. Extensive drug resistance was common, including multiple TAMs and dual-class resistance. As ABC/ddI was the preferred NRTI backbone for pediatric patients on second-line therapy in Zambia prior to 2011, 43% of those on second-line would be predicted to have no fully active NRTIs. ETV would be of limited use in this population. The use of non-thymidine analog based first-line regimens would likely result in less extensive resistance and preserve future treatment options.
(C) 2013 Lippincott Williams & Wilkins, Inc.