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BackgroundShort term efficacy of combination antiretroviral therapy (cART) in resource-constrained settings is comparable to that found in western studies. However, long term data are limited. India has the third largest HIV infected population in the world but the long-term outcome of first line therapy according to the national guidelines has not been evaluated yet. Therefore, we conducted a long-term longitudinal analysis of the efficacy of the national first-line therapy in India from an observational cohort of Indian patients in two different clinical settings.Methodology/principal findingsA total 323 patients who had been on ART for a median of 23 months and achieved virological suppression 2000 copies/mL. Adherence and treatment interruptions (>48 h) were assessed via self-report. In the studied patients, the median duration of viral suppression was 44 months; 15.8% of patients showed viral rebound, and 2.8% viral failure. Viral rebound or failure was significantly negatively related to perfect adherence (100% adherence and no treatment interruption >48 hrs). Virological re-suppression in the subsequent visit was observed in three patients without any change in therapy despite the presence of key mutations.Conclusion/significanceOur study reports for the first time, a good long-term response to the first line therapy for a median of nearly four years although a less than perfect adherence increases the risk for treatment failure and subsequent drug resistance development. The empirical findings in this study also indicate the overall success of the Indian ART program in two different settings which likely are representative of other clinics that operate under the national guidelines.

IntroductionRoutine HIV viral load (VL) testing is not available in India. We compared test performance characteristics of immunologic failure (IF) against the gold standard of virologic failure (VF), examined evolution of drug resistance among those who stayed on a failing regimen because they did not meet criteria for IF and assessed implications for second-line therapy.MethodsParticipants on first-line highly active antiretroviral therapy (HAART) in Bangalore, India, were monitored for 24 months at six-month intervals, with CD4 count, VL and genotype, if VL>1000 copies/ml. Standard WHO criteria were used to define IF; VF was defined as having two consecutive VL>1000 copies/ml or one VL>10,000 copies/ml. Resistance was assessed using standard International AIDS Society-USA (IAS-USA) recommendations.ResultsOf 522 participants (67.6% male, mean age of 37.5; 85.1% on nevirapine-based and 40.4% on d4T-containing regimens), 57 (10.9%) had VF, 38 (7.3%) had IF and 13 (2.5%) had both VF and IF. The sensitivity of immunologic criteria to detect VF was 22.8%, specificity was 94.6% and positive predictive value was 34.2%. Forty-four participants with VF only continued on their failing first-line regimen; by the end of the study period, 90.9% had M184V, 63.6% had thymidine analogue mutations (TAMs), 34.1% had resistance to tenofovir, and 63.6% had resistance to etravirine.ConclusionsWHO IF criteria have low sensitivity for detecting VF, and the presence of IF poorly predicts VF. Relying on CD4 counts leads to unnecessary switches to second-line HAART and continuation of failing regimens, jeopardizing future therapeutic options. Universal access to VL monitoring would avoid costly switches to second-line HAART and preserve future treatment options.

The article discusses the significance of reliable and valid adherence to study highly active antiretroviral therapy adherence in India. It indicates that consistent adherence to antiretroviral regimens is also important to evaluate the impact of adherence interventions. It notes that adherence must be brief and simple to administer in clinical settings in order to predict viral load.