Co-receptor tropism prediction among 1045 Indian HIV-1 subtype C sequences: Therapeutic implications for India

<p>Abstract</p> <p><b>Background</b></p> <p>Understanding co-receptor tropism of HIV-1 strains circulating in India will provide key analytical leverage for assessing the potential usefulness of newer antiretroviral drugs such as chemokine co-receptor antagonists among Indian HIV-infected populations. The objective of this study was to determine using <it>in silico </it>methods, HIV-1 tropism among a large number of Indian isolates both from primary clinical isolates as well as from database-derived sequences.</p> <p>Results</p> <p>R5-tropism was seen in 96.8% of a total of 1045 HIV-1 subtype C Indian sequences. Co-receptor prediction of 15 primary clinical isolates detected two X4-tropic strains using the C-PSSM matrix. R5-tropic HIV-1 subtype C V3 sequences were conserved to a greater extent than X4-tropic strains. X4-tropic strains were obtained from subjects who had a significantly longer time since HIV diagnosis (96.5 months) compared to R5-tropic strains (20.5 months).</p> <p>Conclusions</p> <p>High prevalence of R5 tropism and greater homogeneity of the V3 sequence among HIV-1 subtype C strains in India suggests the potential benefit of CCR5 antagonists as a therapeutic option in India.</p

High rates of adherence and treatment success in a public and public-private HIV clinic in India: potential benefits of standardized national care delivery systems

<p>Abstract</p> <p>Background</p> <p>The massive scale-up of antiretroviral treatment (ART) access worldwide has brought tremendous benefit to populations affected by HIV/AIDS. Optimising HIV care in countries with diverse medical systems is critical; however data on best practices for HIV healthcare delivery in resource-constrained settings are limited. This study aimed to understand patient characteristics and treatment outcomes from different HIV healthcare settings in Bangalore, India.</p> <p>Methods</p> <p>Participants from public, private and public-private HIV healthcare settings were recruited between 2007 and 2009 and were administered structured interviews by trained staff. Self-reported adherence was measured using the visual analogue scale to capture adherence over the past month, and a history of treatment interruptions (defined as having missed medications for more than 48 hours in the past three months). In addition, CD4 count and viral load (VL) were measured; genotyping for drug resistance-associated mutations was performed on those who were in virological failure (VL > 1000 copies/ml).</p> <p>Results</p> <p>A total of 471 individuals were included in the analysis (263 from the public facility, 149 from the public-private facility and 59 from the private center). Private facility patients were more likely to be male, with higher education levels and incomes. More participants reported ≥ 95% adherence among public and public-private groups compared to private participants (public 97%; private 88%; public-private 93%, p < 0.05). Treatment interruptions were lowest among public participants (1%, 10%, 5% respectively, p < 0.001). Although longer clinic waiting times were experienced by more public participants (48%, compared to private 27%, public-private 19%, p < 0.001), adherence barriers were highest among private (31%) compared with public (10%) and public-private (17%, p < 0.001) participants. Viral load was detectable in 13% public, 22% private and 9% public-private participants (p < 0.05) suggesting fewer treatment failures among public and public-private settings. Drug resistance mutations were found more frequently among private facility patients (20%) compared to those from the public (9%) or public-private facility (8%, p < 0.05).</p> <p>Conclusions</p> <p>Adherence and treatment success was significantly higher among patients from public and public-private settings compared with patients from private facilities. These results suggest a possible benefit of the standardized care delivery system established in public and public-private health facilities where counselling by a multi-disciplinary team of workers is integral to provision of ART. Strengthening and increasing public-private partnerships can enhance the success of national ART programs.</p

Out-of-pocket expenditures for childbirth in the context of the Janani Suraksha Yojana (JSY) cash transfer program to promote facility births : who pays and how much? Studies from Madhya Pradesh, India

Background: High out-of-pocket expenditures (OOPE) make delivery care difficult to access for a large proportion of India’s population. Given that home deliveries increase the risk of maternal mortality, in 2005 the Indian Government implemented the Janani Suraksha Yojana (JSY) program to incentivize poor women to deliver in public health facilities by providing a cash transfer upon discharge. We study the OOPE among JSY beneficiaries and women who deliver at home, and predictors of OOPE in two districts of Madhya Pradesh. Methods: September 2013 to April 2015 a cross-sectional community-based survey was performed. All recently delivered women were interviewed to elicit delivery costs, socio-demographic characteristics and delivery related information. Results: Most women (n = 1995, 84 %) delivered in JSY public health facility, the remaining 16 % (n = 386) delivered at home. Women who delivered under JSY program had a higher median, IQR OOPE ($8, 3–18) compared to home ($6, 2–13). Among JSY beneficiaries, poorest women had twice net gain ($20) versus wealthiest ($10) post cash transfer. Informal payments (64 %) and food/baby items (77 %) were the two most common sources of OOPE. OOPE made among JSY beneficiaries was pro-poor: poorer women made proportionally less expenditures compared to wealthier women. In an adjusted model, delivering in a JSY public facility increased odds of incurring expenditures (OR: 1.58, 95 % CI: 1.11–2.25) but at the same time to a 16 % (95 % CI: 0.73–0.96) decrease in the amount paid compared to home deliveries. Conclusions: OOPE is prevalent among JSY beneficiaries as well in home deliveries. In JSY, OOPE varies by income quintile: wealthier quintiles pay more OOPE. However the cash incentive is adequate enough to provide a net gain for all quintiles. OOPE was largely due to indirect costs and not direct medical payments. The program seems to be effective in providing financial protection for the most vulnerable groups

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. METHODS: 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

Influence of Adverse Drug Reactions on Treatment Success: Prospective Cohort Analysis of HIV-Infected Individuals Initiating First-Line Antiretroviral Therapy in India

<div><p>Introduction</p><p>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.</p><p>Methods</p><p>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.</p><p>Results</p><p>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.</p><p>Conclusions</p><p>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.</p><p>Trial registration</p><p>ISRTCN Registry: ISRCTN79261738.</p></div

Recruitment flowchart and study outcomes.

<p>¹ART: Anti- Retroviral Treatment. ²ADR: Adverse Drug Reaction. ³Trial exclusion criteria: Participant in same household, no available phone network. ⁴NRTI: Nucleoside Reverse Transcription Inhibitor. ⁵NNRTI: Non-Nucleoside Reverse Transcription Inhibitor.</p

Incidence rate of adverse drug events (ADRs).

<p>Incidence rate of adverse drug events (ADRs).</p