Trials Methodology Research: what is it and why should India invest in it?

This Viewpoint presents an overview of trials methodology research (TMR) and the case for investing in TMR in India. Randomised controlled trials and other types of clinical research inform evidence-based medicine, but this endeavour is dependent on the quality of such research. TMR is aimed at improving the way in which clinical trials are designed, conducted, analysed, and reported. The evolution of TMR in countries like the UK has been nurtured through dedicated funding support. Similar funding opportunities for TMR in India will help optimise the ethical and methodological rigour of the growing number of trials conducted in India. Such funding could help initiate an interdisciplinary network of key stakeholders in India to lead on TMR priority-setting exercises so that methodological questions of relevance to India are addressed. The establishment of trials methodology hubs will enhance initiatives such as the disease-specific clinical trials networks being set up as part of the National Biopharma Mission in India. We posit that promoting and establishing TMR as a distinct field of study in India will ensure the improvement of our health research ecosystem and call on national and international funding bodies to initiate consultation, consensus building and ringfenced funding for TMR in India.

Feasibility and acceptability pilot of video-based direct observed treatment (vDOT) for supporting antitubercular treatment in South India: a cohort study.

OBJECTIVES: The objective of this study was to assess the feasibility and acceptability of video-based anti-tuberculosis (TB) treatment adherence support in patients with TB (PwTB) in South India. DESIGN: An exploratory cohort. SETTING: Participants were recruited at the TB treatment centre (direct observed treatment short centre) of a tertiary-level teaching facility in Bangalore, Karnataka, South India. PARTICIPANTS: The study enrolled 25 PwTB, with replacement. Adult PwTB who were on drug-sensitive treatment regimens were included, while those who had drug resistant TB were excluded from the study. INTERVENTION: Participants received scheduled adherence reminders and were trained to videorecord themselves swallowing their medication via a mobile application. The application was automated to submit these videos for evaluation. Participants were followed up monthly till treatment completion or withdrawal. OUTCOME MEASURES: Adherence rate and acceptability of video-based directly observed treatment (vDOT). RESULTS: The mean±SD age of the participants was 33±14 years, majority were females (16, 64%), residing in urban areas (24,96%), married (17, 68%) and had access to smart phones (23,92%). A total of 3193 person days of follow-up was completed; of the videos submitted within the first 6 months of enrollment (2501), 94% (2354/2501) were considered 'acceptable' and 16 (64%) participants were optimally adherent (ie, ≥80%). Participant videos improved in quality and a higher proportion met acceptability criteria over time. Twenty-one (84%) participants stated that they found the application easy to learn; 13 (52%) preferred vDOT over DOT. Mixed model logistic regression showed that those who are married are more likely have daily adherence to anti-TB treatment. CONCLUSION: Video-based mobile phone interventions are acceptable to PwTB and the ease of using the application increases with time. To provide patient-centred care, vDOT is a promising option that can be offered to patients for treatment support and adherence monitoring.

Formative acceptance of ingestible biosensors to measure adherence to TB medications.

BACKGROUND: Tuberculosis (TB) represents a significant public health threat in India. Adherence to antitubercular therapy (ATT) is the key to reducing the burden of this infectious disease. Suboptimal adherence to ATT and lack of demonstrated feasibility of current strategies for monitoring ATT adherence highlights the need for alternative adherence monitoring systems. METHODS: A quantitative survey was conducted to assess the acceptance of and willingness to use a digital pill system (DPS) as a tool for monitoring ATT adherence among stakeholders directly involved in the management of patients with TB in India. Participants reviewed a video explaining the DPS and completed a survey, which covered sociodemographics, degree of involvement with TB patients, initial impressions of the DPS, and perceived challenges for deploying the technology in India. Participants were also asked to interpret mock DPS adherence data. RESULTS: The mean age was 34.3 (SD = 7.3), and participants (N = 50) were predominantly male (70%). The sample comprised internists (52%) and pulmonologists (30%), with a median of 4 years' experience (IQR 3, 6) in the management of TB patients. No participants had previously used a DPS, but some reported prior awareness of the technology (22%). Most reported that they would recommend use of a DPS to patients on ATT (76%), and that they would use a DPS in both the intensive and continuation phases of TB management (64%). The majority viewed the DPS (82%) as a useful alternative to directly observed therapy-short course (DOTS), particularly given the ongoing COVID-19 pandemic. Participants reported that a DPS would be most effective in patients at risk of nonadherence (64%), as well as those with past nonadherence (64%). Perceived barriers to DPS implementation included lack of patient willingness (92%), cost (86%), and infrastructure constraints (66%). The majority of participants were able to accurately interpret patterns of adherence (80%), suboptimal adherence (90%), and frank nonadherence (82%) when provided with mock DPS data. CONCLUSIONS: DPS are viewed as an acceptable, feasible, and useful technology for monitoring ATT adherence by stakeholders directly involved in TB management. Future investigations should explore patient acceptance of DPS and pilot demonstration of the system in the TB context.

The Acceptability of Adherence Support via Mobile Phones for Antituberculosis Treatment in South India: Exploratory Study.

BACKGROUND: India has the greatest burden of tuberculosis (TB). However, over 15% of the people on antitubercular therapy (ATT) in India are nonadherent. Several adherence monitoring techniques deployed in India to enhance ATT adherence have had modest effects. Increased adoption of mobile phones and other technologies pose potential solutions to measuring and intervening in ATT adherence. Several technology-based interventions around ATT adherence have been demonstrated in other countries. OBJECTIVE: The objective of our study was to understand the acceptance of mobile phone adherence supports for ATT using self-administered quantitative measures among patients with TB in South India. METHODS: This exploratory study was conducted at a TB treatment center (TTC) at a tertiary care center in Thrissur District, Kerala, India. We recruited 100 patients with TB on ATT using convenience sampling after obtaining written informed consent. Trained study staff administered the questionnaire in Malayalam, commonly spoken in Kerala, India. We used frequency, mean, median, and SD or IQR to describe the data. RESULTS: Of the 100 participants diagnosed with TB on ATT, 90% used mobile phones routinely, and 84% owned a mobile phone. Ninety-five percent of participants knew how to use the calling function, while 65% of them did not know how to use the SMS function on their mobile phone. Overall, 89% of the participants did not consider mobile phone-based ATT adherence interventions an intrusion in their privacy, and 93% did not fear stigma if the adherence reminder was received by someone else. Most (95%) of the study participants preferred mobile phone reminders instead of directly observed treatment, short-course. Voice calls (n=80, 80%) were the more preferred reminder modality than SMS reminders (n=5, 5%). CONCLUSIONS: Mobile phones are likely an acceptable platform to deliver ATT adherence interventions among individuals with TB in South India. Preference of voice call reminders may inform the architecture of future adherence interventions surrounding ATT in South India.

"If I have teeth, I can smile." Experiences with tooth loss and the use of a removable dental prosthesis among people who are partially and completely edentulous in Karnataka, India.

OBJECTIVES: Tooth loss is a phenomenon associated with structural and functional changes, with a negative influence on the oral and general health of an individual. Removable dental prosthesis is commonly fabricated as treatment for tooth loss. However, the perceptions and experiences of individuals during the transition from a dentate to a partially or completely edentulous state and their acceptance of the denture are largely ignored. The objective of this study was to explore the perceptions and experiences during the transition from a dentate state to being partially or completely edentulous in the Indian population. METHODS: Fifteen individuals wearing partial or complete denture prosthesis were interviewed in depth using open-ended questions. These interviews were recorded using a voice-recording device. They were then transcribed, and a coding process was applied using the thematic framework approach to qualitative analysis. FINDINGS: Five themes emerged, namely: (i) Transition from dentulous to partially or completely edentulous state; (ii) Varying experiences with the use of dentures; (iii) Convenience and duration of wearing dentures; (iv) Attitude of dentists towards patients' complaints; (v) Knowledge and preference of available treatment modalities. CONCLUSIONS: The loss of natural teeth seemed to affect the psychological, functional, and social well-being of participants. Tooth loss was believed to be a natural aging process. Costs of treatment deterred the uptake of fixed denture treatment options. However, some participants preferred removable dentures to fixed prosthesis.

An exploration of the oral health beliefs and behaviors of people living with HIV in Mangalore, India: a qualitative study.

INTRODUCTION: People living with HIV (PLWHIV) have increased oral healthcare needs due to an increase in the prevalence of oral and dental diseases. Their oral health is influenced by psychosocial, behavioral and biologic factors. The aim of this study was to explore and obtain a deeper understanding of the oral health beliefs and behaviors of PLWHIV that could potentially affect their oral health. METHODS: We have used the Health Belief Model (HBM) and qualitative methods using in-depth interviews with 16 PLWHIV. Content analysis of the transcribed data was done. The data was grouped under the constructs of the HBM. FINDINGS: The perceived susceptibility to oral diseases and awareness on the importance of good oral health was low. Regular tooth brushing and traditional methods for oral hygiene maintenance were considered beneficial. Regular dental visits were not considered important. Psychosocial issues, time and financial constraints were the barriers. Participants believed that information on oral health should be provided by the health providers in hospitals and dental clinics.  CONCLUSION: The findings on the oral health beliefs and behaviors support the need for education on oral health and preventive healthcare practices among PLWHIV. Oral health promotion should include behavioral change as one of its components.

Trends in snakebite deaths in India from 2000 to 2019 in a nationally representative mortality study.

The World Health Organization call to halve global snakebite deaths by 2030 will require substantial progress in India. We analyzed 2833 snakebite deaths from 611,483 verbal autopsies in the nationally representative Indian Million Death Study from 2001 to 2014, and conducted a systematic literature review from 2000 to 2019 covering 87,590 snakebites. We estimate that India had 1.2 million snakebite deaths (average 58,000/year) from 2000 to 2019. Nearly half occurred at ages 30-69 years and over a quarter in children < 15 years. Most occurred at home in the rural areas. About 70% occurred in eight higher burden states and half during the rainy season and at low altitude. The risk of an Indian dying from snakebite before age 70 is about 1 in 250, but notably higher in some areas. More crudely, we estimate 1.11-1.77 million bites in 2015, of which 70% showed symptoms of envenomation. Prevention and treatment strategies might substantially reduce snakebite mortality in India.

Mobile Health for Tuberculosis Management in South India: Is Video-Based Directly Observed Treatment an Acceptable Alternative?

BACKGROUND: With the availability of low-cost mobile devices and the ease of internet access, mobile health (mHealth) is digitally revolutionizing the health sector even in resource-constrained settings. It is however necessary to assess end-user perceptions before deploying potential interventions. OBJECTIVE: This study aimed to assess the mobile phone usage patterns and the acceptability of mobile phone support during care and treatment in patients with tuberculosis (TB) in South India. METHODS: This exploratory study was conducted at an urban private tertiary care teaching hospital and nearby public primary-level health care facilities in Bangalore, South India. We recruited 185 patients with TB through consecutive sampling. Subsequent to written informed consent, participants responded to an interviewer-administered pretested questionnaire. The questionnaire included questions on demographics, phone usage patterns, and the benefits of using of mobile phone technology to improve health outcomes and treatment adherence. Frequency, mean, median, and SD or interquartile range were used to describe the data. Bivariate associations were assessed between demographics, clinical details, phone usage, and mHealth communication preferences using the chi-square test and odds ratios. Associations with a P value ≤.20 were included in a logistic regression model. A P value of <.05 was considered significant. RESULTS: Of the 185 participants, 151 (81.6%) used a mobile phone, and half of them owned a smartphone. The primary use of the mobile phone was to communicate over voice calls (147/151, 97.4%). The short message service (SMS) text messaging feature was used by only 66/151 (43.7%) mobile phone users. A total of 87 of the 151 mobile phone users (57.6%) knew how to use the camera. Only 41/151 (27.2%) mobile phone users had used their mobile phones to communicate with their health care providers. Although receiving medication reminders via mobile phones was acceptable to all participants, 2 participants considered repeated reminders as an intrusion of their privacy. A majority of the participants (137/185, 74.1%) preferred health communications via voice calls. Of the total participants, 123/185 (66.5%) requested reminders to be sent only at specific times during the day, 22/185 (11.9%) suggested reminders should synchronize with their prescribed medication schedule, whereas 40/185 (21.6%) did not have any time preferences. English literacy was associated with a preference for SMS in comparison with voice calls. Most participants (142/185, 76.8%) preferred video-based directly observed treatment when compared with in-person directly observed treatment. CONCLUSIONS: Although mobile phones for supporting health and treatment adherence were acceptable to patients with TB, mHealth interventions should consider language, mode of communication, and preferred timing for communication to improve uptake.

Tuberculosis notification in a private tertiary care teaching hospital in South India: a mixed-methods study.

OBJECTIVES: India contributes approximately 25% of the 'missing' cases of tuberculosis (TB) globally. Even though ~50% of patients with TB are diagnosed and treated within India's private sector, few are notified to the public healthcare system. India's TB notification policy mandates that all patients with TB are notified through Nikshay (TB notification portal). We undertook this study in a private hospital to assess the proportion notified and factors affecting TB notifications. We explored barriers and probable solutions to TB notification qualitatively from health provider's perspective. STUDY SETTING: Private, tertiary care, teaching hospital in Bengaluru, South India. METHODOLOGY: This was a mixed-methods study. Quantitative component comprised a retrospective review of hospital records between 1 January 2015 and 31 December 2017 to determine TB notifications. The qualitative component comprised key informant interviews and focus groups to elicit the barriers and facilitators of TB notification. RESULTS: Of 3820 patients diagnosed and treated, 885 (23.2%) were notified. Notifications of sputum smear-positive patients were significantly more likely, while notifications of children were less likely. Qualitative analysis yielded themes reflecting the barriers to TB notification and their solutions. Themes related to barriers were: (1) basic diagnostic procedures and treatment promote notification; (2) misconceptions regarding notification and its process are common among healthcare providers; (3) despite a national notification system other factors have prevented notification of all patients; and (4) establishing hospital systems for notification will go a long way in improving notifications. CONCLUSIONS: The proportion of patients with TB notified by the hospital was low. A comprehensive approach both by the hospital management and the national TB programme is necessary for improving notification. This includes improving awareness among healthcare providers about the requirement for TB notifications, establishing a single notification portal in hospital, digitally linking hospital records to Nikshay and designating one person to be responsible for notification.

Perceived usefulness of receiving a potential smoking cessation intervention via mobile phones among smokers in Indonesia.

Background: The use of technology to support healthcare in Indonesia holds new promise in light of decreasing costs of owning mobile devices and ease of access to internet. However, it is necessary to assess end-user perceptions regarding mobile health interventions prior to its implementation. This would throw light on the acceptability of mobile phone communication in bringing about behavioural changes among the target Indonesian population. The aim of this study was to explore the perceived usefulness of receiving a potential smoking cessation intervention via mobile phones. Methods: This is an exploratory cross-sectional study involving current and former adult tobacco smokers residing in Indonesia. Online advertisement and snowballing were used to recruit respondents. Data was collected using a web-based survey over a period of 4 weeks. Those willing to participate signed an online consent and were subsequently directed to the online questionnaire that obtained demographics, tobacco usage patterns, perceived usefulness of a mobile phone smoking cessation application and its design. Results: A total of 161 people who smoked tobacco responded to the online survey. The mean age of the participants was 29.4. Of the 123 respondents, 102 were men. Prior experience with using a mobile phone for health communication (OR 3.6, P=0.014) and those willing to quit smoking (OR 5.1, P=0.043) were likely to perceive a mobile phone smoking cessation intervention as useful. A smartphone application was preferred over text messages, media messages or interactive voice response technology. Content comprising of motivational messages highlighting the methods and benefits of quitting smoking were requested. Conclusion: People who smoke in Indonesia perceived receiving a potential smoking cessation intervention via mobile phones as useful. A multi-component, personalized smartphone application was the desired intervention technique. Such an intervention developed and implemented within a public health program could help address the tobacco epidemic in Indonesia.

Senior Friendly Hospitals: Development and Application of Criteria: A Descriptive Study.

BACKGROUND: The world's population is rapidly aging. Between 2000 and 2050, the proportion of the world's population over the age of 60 will double from about 11% to 22%; more so in the developing countries. The prevalence of frailty and morbidity among the elderly is high. There is a need to assess the "preparedness" of the health care system including hospitals to respond to the needs of the elderly. AIM: 1. To develop criteria for a senior friendly hospital and 2. To assess the feasibility of application of these criteria. MATERIALS AND METHODS: A descriptive study was done at Bangalore, India, involving 100 subjects sampled by purposive sampling. Study population consisted of senior citizens, their caretakers, physicians, hospital support staff, nurses, geriatricians, hospital administrators, and architects. They were interviewed using a validated translated interview schedule. The study consisted of two phases; Phase 1: Developing a checklist to assess senior friendliness of a hospital by using modified Delphi technique. Phase 2: Application of the checklist thus developed to selected hospitals in order to assess the feasibility of administration. The data was then analyzed using Statistical Package for the Social Sciences (SPSS) for frequencies, proportions, central tendency and dispersion, interclass reliability, intraclass reliability, and Cronbach's alpha. RESULTS: A checklist containing 44 items to assess the senior friendliness of a hospital was developed. The checklist was found feasible and easy to administer. CONCLUSIONS: The checklist thus developed to assess senior friendliness of a hospital has wider application as it has a potential to be considered for framing senior friendly hospital guidelines/policies.

Cost-effectiveness analysis of microscopic observation drug susceptibility test versus Xpert MTB/Rif test for diagnosis of pulmonary tuberculosis in HIV patients in Uganda.

BACKGROUND: Microscopic Observation Drug Susceptibility (MODS) and Xpert MTB/Rif (Xpert) are highly sensitive tests for diagnosis of pulmonary tuberculosis (PTB). This study evaluated the cost effectiveness of utilizing MODS versus Xpert for diagnosis of active pulmonary TB in HIV infected patients in Uganda. METHODS: A decision analysis model comparing MODS versus Xpert for TB diagnosis was used. Costs were estimated by measuring and valuing relevant resources required to perform the MODS and Xpert tests. Diagnostic accuracy data of the tests were obtained from systematic reviews involving HIV infected patients. We calculated base values for unit costs and varied several assumptions to obtain the range estimates. Cost effectiveness was expressed as costs per TB patient diagnosed for each of the two diagnostic strategies. Base case analysis was performed using the base estimates for unit cost and diagnostic accuracy of the tests. Sensitivity analysis was performed using a range of value estimates for resources, prevalence, number of tests and diagnostic accuracy. RESULTS: The unit cost of MODS was US$ 6.53 versus US$ 12.41 of Xpert. Consumables accounted for 59 % (US$ 3.84 of 6.53) of the unit cost for MODS and 84 % (US$10.37 of 12.41) of the unit cost for Xpert. The cost effectiveness ratio of the algorithm using MODS was US$ 34 per TB patient diagnosed compared to US$ 71 of the algorithm using Xpert. The algorithm using MODS was more cost-effective compared to the algorithm using Xpert for a wide range of different values of accuracy, cost and TB prevalence. The cost (threshold value), where the algorithm using Xpert was optimal over the algorithm using MODS was US$ 5.92. CONCLUSIONS: MODS versus Xpert was more cost-effective for the diagnosis of PTB among HIV patients in our setting. Efforts to scale-up MODS therefore need to be explored. However, since other non-economic factors may still favour the use of Xpert, the current cost of the Xpert cartridge still needs to be reduced further by more than half, in order to make it economically competitive with MODS.

'The phone reminder is important, but will others get to know about my illness?' Patient perceptions of an mHealth antiretroviral treatment support intervention in the HIVIND trial in South India.

OBJECTIVES: The recent explosion of mHealth applications in the area of HIV care has led to the development of mHealth interventions to support antiretroviral treatment adherence. Several of these interventions have been tested for effectiveness, but few studies have explored patient perspectives of such interventions. Exploring patient perspectives enhances the understanding of how an intervention works or why it does not. We therefore studied perceptions regarding an mHealth adherence intervention within the HIVIND trial in South India. METHODS: The study was conducted at three clinics in South India. The intervention comprised an automated interactive voice response (IVR) call and a pictorial short messaging service (SMS), each delivered weekly. Sixteen purposively selected participants from the intervention arm in the HIVIND trial were interviewed. All participants had completed at least 84 weeks since enrollment in the trial. Perceptions on the usefulness and perceived benefits and risks of receiving the intervention were sought. The interviews were transcribed and analysed using the framework approach to qualitative data analysis. RESULTS: Despite varying perceptions of the intervention, most participants found it useful. The intervention was perceived as a sign of 'care' from the clinic. The IVR call was preferred to the SMS reminder. Two-way communication was preferred to automated calls. Participants also perceived a risk of unintentional disclosure of their HIV status and stigma thereof via the intervention and took initiatives to mitigate this risk. Targeting reminders at those with poor adherence and those in need of social support was suggested. CONCLUSIONS: mHealth adherence interventions go beyond their intended role to provide a sense of care and support to the recipient. Although automated interventions are impersonal, they could be a solution for scale up. Interventions that engage both the recipient and the healthcare provider have greater potential for success. Personalising mHealth interventions could mitigate the risk of stigma and promote their uptake. TRIAL REGISTRATION NUMBER: ISRCTN79261738.

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.

Mobile phones: the next step towards healthcare delivery in rural India?

BACKGROUND: Given the ubiquity of mobile phones, their use to support healthcare in the Indian context is inevitable. It is however necessary to assess end-user perceptions regarding mobile health interventions especially in the rural Indian context prior to its use in healthcare. This would contextualize the use of mobile phone communication for health to 70% of the country's population that resides in rural India. OBJECTIVES: To explore the acceptability of delivering healthcare interventions through mobile phones among users in a village in rural Bangalore. METHODS: This was an exploratory study of 488 mobile phone users, residing in a village, near Bangalore city, Karnataka, South India. A pretested, translated, interviewer-administered questionnaire was used to obtain data on mobile phone usage patterns and acceptability of the mobile phone, as a tool for health-related communication. The data is described using basic statistical measures. RESULTS: The primary use of mobile phones was to make or receive phone calls (100%). Text messaging (SMS) was used by only 70 (14%) of the respondents. Most of the respondents, 484 (99%), were willing to receive health-related information on their mobile phones and did not consider receiving such information, an intrusion into their personal life. While receiving reminders for drug adherence was acceptable to most 479 (98%) of our respondents, 424 (89%) preferred voice calls alone to other forms of communication. Nearly all were willing to use their mobile phones to communicate with health personnel in emergencies and 367 (75%) were willing to consult a doctor via the phone in an acute illness. Factors such as sex, English literacy, employment status, and presence of chronic disease affected preferences regarding mode and content of communication. CONCLUSION: The mobile phone, as a tool for receiving health information and supporting healthcare through mHealth interventions was acceptable in the rural Indian context.

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.

Effect of mobile telephone reminders on treatment outcome in HIV: evidence from a randomised controlled trial in India.

OBJECTIVE: To assess whether customised mobile phone reminders would improve adherence to therapy and thus decrease virological failure among HIV infected patients starting antiretroviral treatment (ART). DESIGN: Randomised controlled trial among HIV infected patients initiating antiretroviral treatment. SETTING: Three diverse healthcare delivery settings in south India: two ambulatory clinics within the Indian national programme and one private HIV healthcare clinic. PARTICIPANTS: 631 HIV infected, ART naïve, adult patients eligible to initiate first line ART were randomly assigned to mobile phone intervention (n=315) or standard care (n=316) and followed for 96 weeks.. INTERVENTION: The intervention consisted of customised, interactive, automated voice reminders, and a pictorial message that were sent weekly to the patients' mobile phones for the duration of the study. MAIN OUTCOME MEASURES: The primary outcome was time to virological failure (viral load >400 copies/mL on two consecutive measurements). Secondary outcomes included ART adherence measured by pill count, death rate, and attrition rate. Suboptimal adherence was defined as mean adherence <95%. RESULTS: Using an intention-to-treat approach we found no observed difference in time to virological failure between the allocation groups: failures in the intervention and standard care arms were 49/315 (15.6%) and 49/316 (15.5%) respectively (unadjusted hazard ratio 0.98, 95% confidence interval 0.67 to 1.47, P=0.95). The rate of virological failure in the intervention and standard care groups were 10.52 and 10.73 per 100 person years respectively. Comparison of suboptimal adherence was similar between both groups (unadjusted incidence rate ratio 1.24, 95% CI 0.93 to 1.65, P=0.14). Incidence proportion of patients with suboptimal adherence was 81/300 (27.0%) in the intervention arm and 65/299 (21.7%) in the standard care arm. The results of analyses adjusted for potential confounders were similar, indicating no significant difference between the allocation groups. Other secondary outcomes such as death and attrition rates, and subgroup analysis also showed comparable results across allocation groups. CONCLUSIONS: In this multicentre randomised controlled trial among ART naïve patients initiating first line ART within the Indian national programme, we found no significant effect of the mobile phone intervention on either time to virological failure or ART adherence at the end of two years of therapy.Trial registration Current Controlled Trials ISRCTN79261738.

'What do I know? Should I participate?' Considerations on participation in HIV related research among HIV infected adults in Bangalore, South India.

BACKGROUND: India has the highest number of HIV infected persons in the world after South Africa. Much HIV related behavioral, clinical and laboratory based research is ongoing in India. Yet little is known on Indian HIV patients' knowledge of research, their processes of decision making and motives for participation. We aimed to explore these areas among HIV infected individuals to understand their reasons for participating in research. METHODOLOGY/PRINCIPAL FINDINGS: This is a cross sectional survey among 173 HIV infected adults at a tertiary level hospital in Bangalore, India, done between October 2010 and January 2011. A pre-tested questionnaire was administered to the participants by trained research assistants to assess their knowledge regarding research, willingness to participate, decision making and determinants of participation. Participants were presented with five hypothetical HIV research studies. Each study had a different level of intervention and time commitment. Of respondents, 103(60%), said that research meant 'to discover something new' and 138(80%) were willing to participate in research. A third of the respondents were unaware of their right to refuse participation. Willingness to participate in research varied with level of intervention. It was the lowest for the hypothetical study involving sensitive questions followed by the hypothetical drug trial; and was the highest for the hypothetical cross sectional questionnaire based study (p<0.0015). Individual health benefits and altruism were the primary motives for participation in research and indicate the presence of therapeutic misconception. Women were less likely to make autonomous decisions for participation in interventional studies. CONCLUSIONS/SIGNIFICANCE: Despite a majority willing to participate, over a third of respondents did not have any knowledge of research or the voluntary nature of participation. This has ethical implications. Researchers need to focus on enabling potential research participants understand the concepts of research, promote autonomous decisions, especially by women and restrict therapeutic misconception.

Supporting adherence to antiretroviral therapy with mobile phone reminders: results from a cohort in South India.

BACKGROUND: Adherence is central to the success of antiretroviral therapy. Supporting adherence has gained importance in HIV care in many national treatment programs. The ubiquity of mobile phones, even in resource-constrained settings, has provided an opportunity to utilize an inexpensive, contextually feasible technology for adherence support in HIV in these settings. We aimed to assess the influence of mobile phone reminders on adherence to antiretroviral therapy in South India. Participant experiences with the intervention were also studied. This is the first report of such an intervention for antiretroviral adherence from India, a country with over 800 million mobile connections. STUDY DESIGN: Quasi-experimental cohort study involving 150 HIV-infected individuals from Bangalore, India, who were on antiretroviral therapy between April and July 2010. The intervention: All participants received two types of adherence reminders on their mobile phones, (i) an automated interactive voice response (IVR) call and (ii) A non-interactive neutral picture short messaging service (SMS), once a week for 6 months. Adherence measured by pill count, was assessed at study recruitment and at months one, three, six, nine and twelve. Participant experiences were assessed at the end of the intervention period. RESULTS: The mean age of the participants was 38 years, 27% were female and 90% urban. Overall, 3,895 IVRs and 3,073 SMSs were sent to the participants over 6 months. Complete case analysis revealed that the proportion of participants with optimal adherence increased from 85% to 91% patients during the intervention period, an effect that was maintained 6 months after the intervention was discontinued (p = 0.016). Both, IVR calls and SMS reminders were considered non-intrusive and not a threat to privacy. A significantly higher proportion agreed that the IVR was helpful compared to the SMS (p<0.001). CONCLUSION: Mobile phone reminders may improve medication adherence in HIV infected individuals in this setting, the effect of which was found to persist for at least 6 months after cessation of the intervention.

Supporting patient adherence to antiretrovirals using mobile phone reminders: patient responses from South India.

There has been exponential growth in the use of mobile phones in India over the last few years, and their potential benefits as a healthcare tool has raised tremendous interest. We used mobile phone reminders to help support adherence to antiretroviral therapy (ART) among HIV patients at an infectious disease clinic in a tertiary hospital in Bangalore. Between March and June 2010, 139 adult HIV patients taking regular ART for at least a month received weekly reminders to support adherence. These reminders consisted of a weekly interactive call and a non-interactive neutral pictorial short message service (SMS). After four weeks of the intervention, participants were interviewed to study perceptions on preference, usefulness, potential stigma and privacy concerns associated with this intervention. Majority of the participants were urban (89%), and had at least a secondary education (85%). A total of 744 calls were made, 545 (76%) of which were received by the participants. In addition, all participants received the weekly pictorial SMS reminder. A month later, 90% of participants reported the intervention as being helpful as medication reminders, and did not feel their privacy was intruded. Participants (87%) reported that they preferred the call as reminders, just 11% favoured SMS reminders alone. Only 59% of participants viewed all the SMSs that were delivered, while 15% never viewed any at all. Participants also denied any discomfort or stigma despite 20% and 13%, respectively, reporting that another person had inadvertently received their reminder call or SMS. Mobile phone interventions are an acceptable way of supporting adherence in this setting. Voice calls rather than SMSs alone seem to be preferred as reminders. Further research to study the influence of this intervention on adherence and health maintenance is warranted.