Second line failure and protease inhibitor resistance in a clinic in Johannesburg, South Africa

Abstract

Background: In resource limited settings, where few options exist for patients failing second line antiretroviral therapy (ART), programmatic approaches to treatment failure must be developed. We report on an approach to standardizing care for patients on second-line in South Africa. Methodology: We conducted a retrospective study of 314 patients on second line protease inhibitor (PI) ART with a HIV-1 RNA >400 copies/ml at Themba Lethu Clinic in Johannesburg, South Africa between March 2012 and September 2013. Patients underwent adherence counselling and repeat viral load testing. Those with a repeat viral load after re-adherence of >1000copies/ml underwent testing for HIV-1 drug resistance if the clinician believed that adherence had improved. Sequences were graded as intermediate or resistant using the Stanford University HIV Drug Resistance Database. Results: Of the 314 patients who underwent adherence counselling, 61% were female. The median age was 40.5 years (IQR 35-47), median CD4 count was 346 cells/mm3 (205-422) and viral load was 6458 copies/ml (IQR 2044-40006). The average length of time on ART since initiation was 5.3 years (IQR 3.2-7.1) and 2.4 years (IQR 1.0- 4.5) on second-line therapy. Compared to other patients on second-line at TLC, more patients that failed second-line failed to supress their viral load at 6 months (53% vs. 15%) and 12 (46% vs. 14%) months after starting second-line. Of the 314, 282 (90%) had ≥1 repeat viral load, 26 (8%) had none, and 6 patients (2%) died or were lost to follow-up. 166 (59%) achieved viral re-suppression (<400 copies/ml) over a median (IQR) of 63 days (87-146). 67 of the 282 (24%) had HIV-1 drug resistance tests done. 21% (14/67) did not amplify, 36% (24/67) had no clinically significant resistance, 15% (10/67) had NRTI resistance without PI resistance, 13% (9/67) had low level PI resistance and 15% (10/67) had significant PI resistance. In total 19 (6%) patients initiated third line (raltegravir, etravirine or boosted darunavir). Half of these patients have had repeat viral load testing and all are suppressed. Conclusions: Although most second line failures remain related to adherence and can be overcome with careful counselling, we found that 15% of patients who underwent HIV drug resistance testing had significant protease inhibitor resistance that required third-line treatment. Strategies for preventing second line failure are critical in areas where limited treatment options exist.

Conference: CROI conference 2014, Boston, USA