Effect of Metformin on Plasma Exposure of Rifampicin, Isoniazid, and Pyrazinamide in Patients on Treatment for Pulmonary Tuberculosis.

BACKGROUND: To evaluate the effect of metformin on the plasma levels of rifampicin, isoniazid, and pyrazinamide in patients with drug-sensitive pulmonary tuberculosis being treated with first-line antituberculosis treatment (ATT) and to assess the influence of gene polymorphisms on the metabolic pathway of metformin and plasma levels of antitubercular drugs. METHODS: Nondiabetic adults aged 18-60 years with pulmonary tuberculosis were randomized to either the standard ATT (ATT group) or ATT plus metformin (METRIF group) groups in a phase IIB clinical trial. An intensive pharmacokinetic study with blood collection at 0 hour (predosing), followed by 1, 2, 4, 6, 8, and 12 hours after dosing was conducted during the first month of treatment in a subset of 60 study participants after a minimum of 14 doses. Plasma concentrations of rifampicin, isoniazid, pyrazinamide, and metformin were measured by high-performance liquid chromatography using validated methods, and pharmacokinetic parameters and OCT1 and MATE1 gene polymorphisms were compared between the groups. RESULTS: Significant increases in the clearance of rifampicin, isoniazid, and pyrazinamide were observed in patients in the METRIF group (n = 29) compared with those in the ATT group (n = 31). The AA genotypes of the single-nucleotide polymorphism of rs2289669 (MATE1) in the METRIF group showed a significantly decreased area under the concentration-time curve to the last observation point and increased clearance of rifampicin. CONCLUSIONS: Metformin altered rifampicin and isoniazid plasma concentrations in patients receiving antituberculosis treatment for pulmonary tuberculosis with little effect on sputum conversion at the end of treatment. Studies with larger sample sizes are needed to understand host drug-drug interactions.

Finding a way forward with the community: qualitative inquiry in the generalized HIV epidemic in Mizoram, India.

Introduction: Mizoram, the northeastern State of India bordering Myanmar, is presently witnessing a burgeoning generalized HIV epidemic along with the highest State-level HIV prevalence among female sex workers (FSWs, 24.7%) and people who inject drugs (PWID,19.8%) in the country. The present study was conducted against such background to understand the current situation of HIV prevention and care services in Mizoram, and capture community voices as well as concerns so that the way forward could be informed appropriately. Methods: The study period was October through December 2020 (in the midst of COVID-restrictions) in the districts of Aizawl, Mamit, Kolasib, Lunglei, and Champhai where HIV prevalence crossed 1% among ante-natal clinic (ANC) attending women. Contrastingly, the national average HIV prevalence among ANC attendees is 0.24%, which formed the basis for selecting the aforementioned five high burden districts for this current inquiry. In-depth-interviews were conducted with community members and youth leaders, vulnerable and general population groups as well as HIV-program officials. Interviews were recorded, transcribed, translated and later coded for analysis following thematic approach. Results: The emerging issues were grouped in three thematic layers; (1) HIV vulnerability, (2) challenges pertaining to prevention and care services, and (3) program elements and future roadmap. Discrimination at the community level, unfriendly behavior of some of the HIV-service staff, occasional interruption in supplies of anti-retroviral treatment and sterile syringes and needles were voiced as deterrents to accessing HIV prevention and care services by the participants. Community engagement, based on restorative approach rather than retribution and ensuring enhanced performance of the district AIDS program control units emerged as necessary programmatic elements. Conclusion: This inquiry highlighted macro-social and structural forces contributing to stigma and discrimination toward people at risk of HIV. It is urgent that HIV-services are re-aligned through de-centralized district level innovations and creation of safer spaces at the physical, societal and familial level. These, even during the time of stress such as a pandemic, would help health services to remain resilient. HIV outreach, sensitization of the community leaders and health-care professionals through strategic communication and ownership of the communities in these endeavors appeared paramount.

Facilitators and barriers to the uptake of COVID-19 vaccine precaution dose among adult population: qualitative analysis across six different states of India.

Introduction: India launched the COVID-19 vaccination drive on 16th January 2021 by vaccinating the adult population above 18 years of age. This was followed by the introduction of an additional precaution dose. As on 18th October 2022, 1,02,66,96,808 (1.02 Billion) first dose and 94, 95, 39,516 (949 Million) second doses of COVID-19 vaccine were administered. However, when compared to the uptake of the primary doses, the precaution dose uptake lagged behind with only 21,75, 12,721 (217 million) doses administered. Even though, the uptake of the primary doses remained optimal, irrespective of different interventions by the Government of India, the uptake of the precaution dose remained poor. In this context, the Ministry of Health & Family Welfare wanted to understand the facilitators and Barriers for precaution dose uptake among adults so that future immunization campaigns could address these issues. Methods: An exploratory qualitative study was conducted to assess the facilitators and barriers for COVID-19 precaution dose uptake at community level across 6 different states in India. From each of the states, two districts with the highest and lowest rates of COVID-19 vaccine precaution dose uptake were selected. In each of these districts, 2 block Primary Healthcare Centres (PHCs), one with high and one with low uptake were identified. Within these block PHCs, a PHC field area with high and low precaution dose uptakes was identified. From the identified sites a minimum of four IDIs, four FGDs were conducted among the community members. KIIs of the State Immunization Officers, District Immunisation Officers, PHC Medical Officers, healthcare workers like Accredited Social Health Activist/Auxiliary Nurse Midwife were also conducted. The data was audio recorded and it was transcribed, translated and analysed using framework approach. Results: It was observed that rise in COVID-19 cases prompted the community to take the precaution dose, this along with the cost of hospitalization and the number of productive days being lost as a result of being infected resulted in vaccine uptake. The fear of non-availability of COVID-19 vaccines latter on also prompted people for vaccine uptake. While the barriers were, poor accessibility to vaccination centers, long hours of travel, poor road connectivity and lack of transportation facilities. However, the most prominent barriers observed across all study sites was that a sense of pandemic fatigue and complacency had developed both among the providers as well as the beneficiaries. Other barriers include differences in vaccination schedules and longer duration between the primary doses of some vaccines. Media was identified to be both a barrier and facilitator for Covid-19 Precaution dose uptake. Even though media played an important role in disseminating information in the beginning of the campaign, it was soon followed by the circulation of both misinformation and disinformation. Discussion: The study identified that dissemination of accurate information and community involvement at each stage of planning and implementation are crucial for the success of any campaign. Efforts should be constantly made to address and re-invent strategies that will be most suitable for the needs of the community. Therefore, in order to ensure successful vaccination campaigns, it is crucial that along with political will it is also important to have a decentralized approach with inter-sectoral coordination with different stakeholders such as healthcare workers, community members and the different departments such as the local self-governments, education department, law & order department etc. These lessons learnt from COVID-19 vaccination campaigns must not be forgotten and must be applied in future vaccination campaigns and while framing public health policies.

HIV epidemic in Mizoram, India: A rapid review to inform future responses.

Background & objectives: Mizoram, a northeastern State of India bordering Myanmar, is home to several tribal clans under the ethnic group Mizo: Renthelei, Ralte, Paite, Lai, Hmar, Lusei, Mara, Thado and Kuki. Mizos also reside in the neighbouring northeastern States of Tripura, Assam, Manipur and Nagaland. The majority of Mizo people outside India live across the border in the neighbouring Chin State and Sagaing Region of Myanmar. Over the last decade, Mizoram witnessed a concerning level of rise in HIV prevalence among the general population. The present rapid review was conducted to identify various interventions that could help curb this rising trend. Methods: An electronic search strategy with broad domains of 'HIV/AIDS', 'key population', 'community engagement' and 'interventions in Mizoram' using PubMed, Embase and Cochrane was adopted; grey literature were also accessed. Evidence, thus gleaned, were synthesized. Results: Twenty eight resource materials comprising articles, reports and dissertations contributed to the current review. Changing tribal social support structure, early initiation of drugs, sexual debut at an early age and drug-sex interface were identified as factors associated with the progression of HIV epidemic in the State. Issues pertaining to the migration of people across the borders and easy access to drugs continue to be of concern. Churches and youth leaders have a strong influence on the society, at times even constraining access of key population groups to HIV prevention and care services. Tackling stigma and discrimination, ensuring uninterrupted HIV services and creation of an enabling environment in this context seems urgently needed. Incarcerated people in the State have been found with a high level of HIV infection and their linkages with prevention and care services need strengthening. Interpretation & conclusions: This review underscores the importance of drawing upon successful intervention examples from the past such as 'Friends on Friday' and Red Ribbon Clubs. Active engagement of community-based organizations in programme planning, implementation and monitoring is essential. Establishment of harm reduction interventions for general and key populations paired with strategic communication appear to be the need of the hour.

Randomized Trial of Metformin With Anti-Tuberculosis Drugs for Early Sputum Conversion in Adults With Pulmonary Tuberculosis.

BACKGROUND: Metformin, by reducing intracellular Mycobacterium tuberculosis growth, can be considered an adjunctive therapy to anti-tuberculosis treatment (ATT). We determined whether metformin with standard ATT reduces time to sputum culture conversion and tissue inflammation in adults with pulmonary tuberculosis (PTB). METHODS: In a randomized, 8-week, clinical trial, newly diagnosed, culture-positive PTB patients were randomized to standard ATT (HREZ = control arm) or standard ATT plus daily 1000 mg metformin (MET-HREZ = Metformin with Rifampicin [METRIF] arm) for 8 weeks during 2018-2020 at 5 sites in India. The primary end point was time to sputum culture conversion by liquid culture during 8 weeks of ATT. Plasma inflammatory markers were estimated in a subset. A Cox proportional hazard model was used to estimate time and predictors of culture conversion. RESULTS: Of the 322 patients randomized, 239 (74%) were male, and 212 (66%) had bilateral disease on chest radiograph with 54 (18%) showing cavitation. The median time to sputum culture conversion by liquid culture was 42 days in the METRIF arm and 41 days in the control arm (hazard ratio, 0.8; 95% confidence interval [CI], .624-1.019). After 8 weeks of ATT, cavitary lesions on X-ray (7, 5.3% vs 18, 12.9%; relative risk, 0.42; 95% CI, .18-.96; P = .041) and inflammatory markers were significantly lower in the METRIF arm. Higher body mass index and lower sputum smear grading were associated with faster sputum culture conversion. CONCLUSIONS: The addition of metformin to standard ATT did not hasten sputum culture conversion but diminished excess inflammation, thus reducing lung tissue damage as seen by faster clearance on X-ray and reduced inflammatory markers. CLINICAL TRIALS REGISTRATION: Clinical Trial Registry of India (CTRI/2018/01/011176).

Community-based point-of-care testing to identify new HIV infections: A cross-sectional study from Pune, India.

ABSTRACT: The World Health Organization recommends point-of-care testing (POCT) to detect human immunodeficiency virus (HIV) infected individuals in the community. This will help improve treatment coverage through detection of HIV infection among those who are unaware of their status.This study was planned with an objective to investigate the feasibility and acceptability of POCT for HIV in the community.A community-based cross-sectional study was conducted in rural and peri-urban areas of Pune, India. These sites were selected based on the distance from the nearest HIV testing center. Testing locations were identified in consultation with the local stakeholders and grass-root health workers to identify and capture the priority population. The POCT was performed on blood samples collected by the finger-prick method.The proportion of participants seeking HIV tests for the first time was 79.6% that signifies the feasibility of POCT. The acceptability in the peri-urban and rural areas was 70.2% and 69.7%, respectively. POCT was performed at construction sites (24.9%), nearby industries (16.1%) and parking areas of long-distance trucks (8.1%) in the peri-urban area. Three newly diagnosed HIV-infected participants (0.1%) were detected from the peri-urban areas but none from the rural areas. Two of the newly diagnosed participants and their spouses were linked to care.There was a high acceptability of POCT and wider coverage of priority population with a strategy of testing at places preferable to the study population. Therefore, we believe that community-based POCT is a promising tool for improving HIV testing coverage even in low prevalence settings with the concentrated HIV epidemic.

A Qualitative Exploration to Understand the Sexual Behavior and Needs of Young Adults: A Study Among College Students of Pune, India.

OBJECTIVE: Youth and adolescents are the priority population to target the interventions as risky behaviors persist and they contribute to almost half of the new Human immunodeficiency virus (HIV) infections. The youth in India have a unique and diverse need of sex health education. The present study was conducted with the objective to understand their sexual behavior and requirements of sexual health. METHODS: Focus group discussions were conducted among 74 college students, separately for boys and girls. The participant students were from different streams of education. The domains of enquiry were related to the relationships, risk behaviors, sources of information and use of technology for sex health education. The qualitative data was analyzed based on the themes and subthemes derived from these discussions. RESULTS: A majority of the youth favoured active involvement of parents, school teachers in sex health education. They suggested that better-informed parents lead to better-informed adolescents. Open discussion with experts was also desired by the students. The use of mobile/web based application for sex health education and awareness about HIV and sexually transmitted infections (STIs) was preferred, however, they suggested that based on personal requirements, individual need based counseling and guidance is important. CONCLUSIONS: Active parental involvement and open discussions on sexuality were the preferred options by the student to seek the knowledge and guidance. Innovative mobile application for sex health education will be useful for the young adults for information and communication. The study highlighted a need to develop a holistic approach to generate a culturally-sensitive sex health education and life skills model.

FcγRIIIa receptor polymorphism influences NK cell mediated ADCC activity against HIV.

BACKGROUND: HIV-specific Antibody Dependent Cell Cytotoxicity (ADCC) has shown to be important in HIV control and resistance. The ADCC is mediated primarily by natural killer cell activated through the binding of FcγRIIIa receptor to the Fc portion of antibody bound to the antigen expressed on the infected cells. However, no data is available on the influence of the polymorphism in FcγRIIIa receptor on HIV-specific ADCC response. METHODS: The Sanger's method of sequencing was used to sequence the exon of FcγRIIIa receptor while the ADCC activity was determined using NK cell activation assay. The polymorphism in FcγRIIIa receptor was assessed in HIV-infected Indian individuals with or without HIV-specific ADCC antibodies and its influence on the magnitude of HIV-specific ADCC responses was analyzed. RESULTS: Two polymorphisms: V176F (rs396991) and Y158H (rs396716) were observed. The Y158H polymorphism is reported for the first time in Indian population. Both, V176F (V/V genotype) (p = 0.004) and Y158H (Y/H genotype) (p = 0.032) were found to be significantly associated with higher magnitude of HIV-specific ADCC response. CONCLUSION: The study underscores the role of polymorphism in the FcγRIIIa receptor on HIV-specific ADCC response and suggests that the screening of the individuals for FcγRIIIa-V176F and Y158H polymorphisms could be useful for prediction of efficient treatment in monoclonal antibody-based therapies aimed at ADCC in HIV infection.

Persons living with HIV continue to present late for care: A trend analysis from 2011 to 2015.

CONTEXT: The clinical and prevention benefits of early initiation of antiretroviral therapy (ART) have led to the adoption of test and treat policy for HIV. Early diagnosis of HIV is crucial for maximal benefits from ART. AIMS: This study aims to assess trends in CD4 cell counts at diagnosis and determinants of late presentation. SETTINGS AND DESIGN: We analyzed 5-year data from a free HIV/sexually transmitted infection referral clinic immune. SUBJECTS AND METHODS: Persons presenting for HIV testing from January 2011 to December 2015, for whom CD4 cell count results were available within 3 months of HIV diagnosis, were included in the analysis. Persons on ART were excluded from the study. STATISTICAL ANALYSIS: The predictors of CD4 cell count at presentation were assessed using univariate and multivariate linear regression. RESULTS: Of 1001 persons diagnosed HIV-1 positive, 659 had received CD4 test within 3 months of diagnosis. The median CD4 count at presentation ranged from 212 to 352 cells/cmm in these 5 years and did not show any significant change with time. Nearly 40% had CD4 cell counts below 200 cells/cmm (AIDS); additionally, 23% presented below 350 cells/cmm. Older age (beta: -5.78; P = 0.001), education above matriculation (beta: -123.72; P = 0.014), having current opportunistic infections (beta: -173.58; P = 0.037), and being symptomatic (beta: -101.8; P = 0.002) were predictors of presenting at lower CD4 counts. CONCLUSION: Between 2011 and 2015, persons with HIV continued to present late in spite of changes in ART access program. Education focused on the benefits of early diagnosis and availability of free immediate treatment in the public sector, are crucial to the achievement of the India's 90-90-90 goals.

Differing HIV vulnerability among female sex workers in a high HIV burden Indian state.

INTRODUCTION: The HIV sentinel surveillance [HSS] conducted in 2010-11 among female sex workers [FSW] in the state of Maharashtra, India provided an opportunity to assess characteristics of different types of FSWs and their HIV risk. It is important for India's National AIDS Control Program, to understand the differences in vulnerability among these FSW, in order to define more specific and effective risk reduction intervention strategies. Therefore, we analyzed data from HSS with the objective of understanding the HIV vulnerability among different types of FSW in Maharashtra. MATERIAL AND METHODS: Cross sectional data collected as a part of HSS among FSWs in year 2010-11 from 21 sentinel sites in the state of Maharashtra were analyzed to understand the vulnerability and characteristics of different types of female sex workers based on their place of solicitation using multinomial logistic regression. RESULTS: While the HIV prevalence was 6.6% among all FSWs, it was 9.9% among brothel based [BB], 9% among street based [SB] and 3.1% and 3.7% among home based [HB], and bar based [Bar-B] sex workers respectively. SB FSWs were least likely to be located in HIV low burden districts [ANC] [ARRR: 0.61[95% CI: 0.49, 0.77]], but were 6 times more likely to be recently [<1 year] involved in sex work [ARRR: 6.15 [95% CI: 3.15, 12.0]]. The number of clients of SB FSWs in the preceding week were lower than 11% [ARRR: 0.89 [95%CI: 0.87, 0.90]] as compared to the BB FSWs denoting lesser client load. The duration since last paid sex was shorter [ARRR: 0.94[95%CI: 0.91, 0.96]] as compared to the BB FSWs. CONCLUSION: Street based FSWs have emerged as one of the most vulnerable types of FSW with a high HIV prevalence similar to BB FSWs. Our study reveals that they have more frequent sex acts despite lower client loads, and are more likely to be located in districts highly affected by HIV (ANC prevalence >1%). We identify them as a group to be focused on for prevention interventions and it is likely that they would be easily amenable to novel interventions due to their higher literacy rate as compared to other typologies.