Longitudinal Analysis of Adherence to First-Line Antiretroviral Therapy: Evidence of Treatment Sustainability from an Indian HIV Cohort.

INTRODUCTION: Given the chronic nature of HIV infection and the need for life-long antiretroviral therapy (ART), maintaining long-term optimal adherence is an important strategy for maximizing treatment success. In order to understand better the dynamic nature of adherence behaviors in India where complex cultural and logistic features prevail, we assessed the patterns, trajectories and time-dependent predictors of adherence levels in relation to virological failure among individuals initiating first-line ART in India. METHODS: Between July 2010 and August 2013, eligible ART-naïve HIV-infected individuals newly initiating first-line ART within the national program at three sites in southern India were enrolled and monitored for two years. ART included zidovudine/stavudine/tenofovir plus lamivudine plus nevirapine/efavirenz. Patients were assessed using clinical, laboratory and adherence parameters. Every three months, medication adherence was measured using pill count, and a structured questionnaire on adherence barriers was administered. Optimal adherence was defined as mean adherence ≥95%. Statistical analysis was performed using a bivariate and a multivariate model of all identified covariates. Adherence trends and determinants were modeled as rate ratios using generalized estimating equation analysis in a Poisson distribution. RESULTS: A total of 599 eligible ART-naïve patients participated in the study, and contributed a total of 921 person-years of observation time. Women constituted 43% and mean CD4 count prior to initiating ART was 192 cells/mm3. Overall mean adherence among all patients was 95.4%. The proportion of patients optimally adherent was 75.6%. Predictors of optimal adherence included older age (≥40 years), high school-level education and beyond, lower drug toxicity-related ART interruption, full disclosure, sense of satisfaction with one's own health and patient's perception of having good access to health-care services. Adherence was inversely proportional to virological failure (IRR 0.55, 95%CI 0.44-0.69 p<0.001). Drug toxicity and stigma-related barriers were significantly associated with virological failure, while forgetfulness was not associated with virological failure. CONCLUSION: Our study highlights the overall high level of medication adherence among individuals initiating ART within the Indian national program. Primary factors contributing towards poor adherence and subsequent virological failure in the proportion of individuals with poor adherence included drug toxicity, perceived stigma and poor access to health care services. Strategies that may contribute towards improved adherence include minimizing drug interruptions for medical reasons, use of newer ART regimens with better safety profiles and increasing access with more link ART centers that decentralize ART dispensing systems to individuals.

Mobile phones to support adherence to antiretroviral therapy: what would it cost the Indian National AIDS Control Programme?

INTRODUCTION: Adherence to antiretroviral treatment (ART) is critical to maintaining health and good clinical outcomes in people living with HIV/AIDS. To address poor treatment adherence, low-cost interventions using mobile communication technology are being studied. While there are some studies that show an effect of mobile phone reminders on adherence to ART, none has reported on the costs of such reminders for national AIDS programmes. This paper aims to study the costs of mobile phone reminder strategies (mHealth interventions) to support adherence in the context of India's National AIDS Control Program (NACP). METHODS: The study was undertaken at two tertiary level teaching hospitals that implement the NACP in Karnataka state, South India. Costs for a mobile phone reminder application to support adherence, implemented at these sites (i.e. weekly calls, messages or both) were studied. Costs were collected based on the concept of avoidable costs specific to the application. The costs that were assessed were one-time costs and recurrent costs that included fixed and variable costs. A sequential procedure for costing was used. Costs were calculated at national-programme level, individual ART-centre level and individual patient level from the NACP's perspective. The assessed costs were pooled to obtain an annual cost per patient. The type of application, number of ART centres and number of patients on ART were varied in a sensitivity analysis of costs. RESULTS: The Indian NACP would incur a cost of between 79 and 110 INR (USD 1.27-1.77) per patient per year, based on the type of reminder, the number of patients on ART and the number of functioning ART centres. The total programme costs for a scale-up of the mHealth intervention to reach the one million patients expected to be on treatment by 2017 is estimated to be 0.36% of the total five-year national-programme budget. CONCLUSIONS: The cost of the mHealth intervention for ART-adherence support in the context of the Indian NACP is low and is facilitated by the low cost of mobile communication in the country. Extending the use of mobile communication applications beyond adherence support under the national programme could be done relatively inexpensively.

Influence of adverse drug reactions on treatment success: prospective cohort analysis of HIV-infected individuals initiating first-line antiretroviral therapy in India.

INTRODUCTION: Adverse drug reactions related to antiretroviral therapy (ART) remain a challenge in resource-limited settings, often causing significant morbidity and impaired adherence leading to treatment failure. This 2-year prospective study aimed to describe patterns and predictors of adverse reactions to first-line ART and assess the impact of these events on treatment success. METHODS: Between 2010-2013, 321 ART-naïve eligible adults were enrolled at two clinics in southern India. ART regimens included zidovudine or stavudine plus lamivudine, plus nevirapine or efavirenz. Pill count adherence, immunological and virological monitoring, and laboratory-based adverse drug reactions were measured prospectively and analyzed. RESULTS: Among 321 patients in the study, 289 (90.0%) patients experienced at least 1 adverse reaction, and 85 (26.5%) experienced at least 1 severe reaction. The incidence rate was 52 and 15 per 100 person-years for all reactions and severe reactions respectively. The cumulative incidence of zidovudine-induced anemia was 37.1% over 2 years. At 12 and 24 months, the proportion of patients with optimal adherence, undetectable viral load and CD4 counts >350 cells/mm3 were similar between patients who experienced or did not experience severe adverse drug reactions. CONCLUSIONS: Our results highlight the high frequency of ART-related adverse drug reactions among individuals initiating first-line ART in India, underscoring the importance of detailed counseling and monitoring for maintaining ART durability. Severe drug-induced anemia needs to be addressed urgently with alternative first-line agents, and close laboratory surveillance. High treatment efficacy despite decreased drug safety seen here may be because patients have limited treatment options. Our results support the use of currently recommended safer first-line ART regimens that minimize the risk of severe life-threatening toxicities and provide for a better quality of life. TRIAL REGISTRATION: ISRTCN Registry: ISRCTN79261738.