A study of the genotypic resistance patterns in patients failing first line anti-retroviral therapy regimen in Zambia

Abstract

Background: Few reports have described the drug resistance patterns of patients failing antiretroviral therapy (ART) in areas where HIV subtype C is predominant, and there is little data from Zambia in particular.Aims: To evaluate the pattern of resistance in patients failing first line regimens in Zambia and determine the impact of first line regimen resistance on second line therapy options. A secondary aim was to evaluate the frequency of non-C HIV subtypes.Methodology: Charts from patients failing first-line therapy at three urban, outpatientART clinics (Chreso, Circle of Hope and the Pediatric Center of Excellence at UTH) were reviewed. All available genotypes that were done in patients failing first line ART regimen by December 2010 were included for analysis. The first-line regimen was defined as NNRTI based HAART regimen according to 2004/ 2007 Zambian guidelines. The regimen at failure, and any previous ARV exposure, duration of treatment, the subtype and the viral load were recorded Results: A total of 126 genotypes were analyzed, 92% of which were from pediatric patients and 8% from adult patients; of these, 19% were found to be wild type while 81% were found to have at least one major mutation. M184V was most common (83.3%), followed by NNRTI mutations (K103 and Y181, 76.4%), and then thymidine analog mutations (TAMs, 59%); 43% of patients had ≥2TAMS. K65R was found in one case of a patient failing on AZT and another one failing on d4T, both in subtype C. 38% of patients were predicted to be resistant to Etravirine (ETR). Subtype C/C was found to be predominant at 95.2%; other subtypes identified were B/C (2.4%), D/C (1.6%) and B/B (0.8%).Conclusion: The majority of patients failing first line therapy in Zambia have typical mutations found in subtype B populations. Given that ABC/ddI was the preferred NRTI backbone for the second line regimen for pediatric patients in Zambia before the new 2010 guidelines were launched, 43% of patients on this second line regimen would be predicted to have no fully active agents in their NRTI backbone. Although NNRTIs resistance mutations take long to get archived, they may not be seen in situations like here in Zambia where genotyping is not immediately done after first line failure (i.e. after NNRTI failure).Etravirine (ETR) is therefore likely to be of limited use as a third line agent in this population, and its use should always be guided by a genotype and routine viral load monitoring. A single case of K65R to AZT exposure in subtype C was an unexpected finding.