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Introduction Tuberculosis (TB) continues to be one of the deadliest infectious diseases over the centuries, killing more people worldwide than any other single infectious disease. There is an urgent need for additional strategies which can expedite efforts to combat TB including a preventive vaccine. In this endeavour, we have developed a protocol for a multisite, double-blind, placebo-controlled clinical trial in India that aims to evaluate the efficacy and safety of two TB vaccines; namely, VPM1002 and Immuvac (M.w) (Mycobacterium Indicus Pranii) (MIP) among healthy household contacts (HHCs) of sputum smear-positive pulmonary TB (PTB) patients.Methods and analysis In the three-arm randomised double-blind placebo-controlled trial study protocol, a total of 12 000 HHCs (aged 6−99 years) of sputum smear-positive PTB patients will be randomised to receive either of the two vaccine candidates VPM1002 and MIP or placebo. The primary efficacy endpoint is the prevention of microbiologically confirmed TB. Secondary endpoints will include (1) prevention against Latent TB infection, (2) incidence of adverse events and serious adverse events in study participants, (3) efficacy of vaccine in prevention of PTB/extra PTB in different age groups (6–18 years, 19–35 years, 36–60 years and above 60 years) and (4) immunogenicity of VPM1002 and MIP at month 2 and month 6 after first vaccination in terms of flow cytometric analysis of M.Tb specific CD4+ and CD8+ T cells secreting cytokines and Luminex assays for the presence of different cytokines in the sera and supernatants of peripheral blood mononuclear cells cultures stimulated with whole cell lysates of M.Tb and subsequently similar analysis for the cases who develop TB postvaccination during the follow-up period.Ethics and dissemination Ethics committees’ approvals have been granted by the Institutional Human Ethics Committees of all participating centres in this study and the names of the ethics committees and approvals are as follows: (1) National Institute for Research in Tuberculosis (NIRT)-Chennai (including subsites): ECR/135/Inst/TN/2013/RR-19, Approval No. 390/NIRT-Institutional Ethics Committee (IEC)/2018 dated 5 December 2018 (NIRT-Madurai-ECR/1365/Inst/TN/2020; approval dated 8 June 2020; NIRT, Vellore: ECR/1215/Inst/TN/2019; approval dated 26 September 2020); (2) All India Institute of Medical Sciences (AIIMS), Delhi (including subsites)-Institute Ethics Committee, ECR/547/Inst/DL/2014/RR-17 ECR/538/Inst/DL/2014/RR-20; approval No.IEC-385/06-07-2018, approval OP-28/05.04.2019 and SFH- ECR/593/Inst/DL/2014/RR-20 IEC/VMMC/SJH/project/2019-05/25 ; 23 May 2019; (3) National Institute of Tuberculosis and Respiratory Diseases (NITRD), Delhi: ECR/315/Inst/DL/2013/RR-19; approval IEC-No-NITRD/EC/2019/9004; 8 January 2019; (4) Pune-National AIDS Research Institute (NARI) and subsite-ECR/23/Inst/MH/2013/RR-19; IEC-NARI/EC/approval/2018/196; 29 May 2018; (5) Regional Medical Research Centre-Bhubaneshwar-ECR/911/Inst/OR-2017/RR-21; approval, dated 25 April 2018; Subsites- AIIMS, Bhubaneshwar ECR/534/Inst/OD/2014/RR-17 and 20 approval No. T/EMF/Pulm. Med/19/01 dated 13 May 2019; SCB, Cuttack No. No.ECR/84/Inst/OR/2013/RR-20; approval no.186 dated 7 February 2020; (6) NTI-Bengaluru: Ethics Committee-No-ECR/1819/Inst/KA/2019; approval No NTI-IEC/1.2019/principal investigator, dated 31 January 2019; (7) BMMRC, Hyderabad- ECR/450/Inst/AP/2013/RR-16 approval No. 779/BMMRC/2018/IEC, dated 11 June 2018 (Subsite Share India- Mediciti Ethics Committee-ECR/283/Inst/AP/2013/RR-20; Approval no. EC/11/VII/2K20(1) dated 11 July 2020) and (8) SJMC-Bengaluru: ECR/238/Inst/KA/2013/RR-19; approval IEC/1/491/2020; 7 August 2020.The trial findings will be published in accordance with the Consolidated Standards of Reporting Trials guidance. The results of this clinical trial will be presented at scientific conferences and disseminated through publications in peer-reviewed journals, conference presentations and shared with Ministry of Health and Family Welfare, policy-makers and other stakeholders.Trial registration number CTRI/2019/01/017026.

Abstract Introduction HIV self‐testing (HIVST) has been shown to increase the uptake of HIV testing and help achieve the UNAIDS 95‐95‐95 targets. This study assessed the acceptability, usability (ease of use and result interpretation) and the willingness to pay for HIVST kits distributed through three distribution models, namely the community‐based, PLHIV network‐led and private practitioners models, in India. Methods This cross‐sectional study was implemented across 14 states in India between September 2021 and June 2022. All participants could choose between blood‐based or oral‐fluid‐based test kits. Participants were shown a test‐kit usage demonstration video, and pre‐ and post‐test counselling was provided for all. Participants were followed‐up after testing, and if reported reactive, were further supported for linkage to confirmatory testing and antiretroviral therapy (ART) initiation. Results Among the 90,605 participants found eligible, 88,080 (97%) accepted an HIVST kit. Among the 87,976 who reported using an HIVST kit, 45,207 (51%) preferred a blood‐based kit, and 42,120 (48%) reported testing for the first time. For future testing, 77,064 (88%) reported preferring HIVST over other HIV testing methods. Among those who used the kit, 83,308 (95%) found the kit easy to use, and 83,237 (95%) reported that the test results were easy to interpret. Among those who preferred HIVST for future use, 52,136 (69%) were willing to pay for the kit, with 35,854 (69%) of those willing to pay less than US$ 1.20. Only one instance of social harm was reported, with a participant reporting suicidal tendencies due to discord with their partner. Out of 328 participants (0.4%) who tested reactive with HIVST, 291 (89%) were linked to confirmatory testing; of these, 254 were confirmed HIV positive, and 216 (85%) successfully initiated ART. Conclusions Overall, we report that nearly all participants were willing to accept HIVST, found the test kits easy to use and interpret, and about two‐thirds were willing to pay for HIVST. Given the high levels of acceptance and the ability to reach a large proportion of first‐time testers, HIVST in India could contribute to achieving the UNAIDS first 95 and ending the HIV epidemic.

Summary: Background: Emerging research indicates growing concern over long COVID globally, although there have been limited studies that estimate population burden. We aimed to estimate the burden of long COVID in three districts of Haryana, India, using an opportunity to link a seroprevalence study to follow-up survey of symptoms associated with long COVID. Methods: We used a population-based seroprevalence survey for COVID-19 conducted in September 2021 across Haryana, India. Adults from three purposively selected districts (Rohtak, Gurugram, and Jhajjar) were eligible to participate; 2205 of 3213 consented to participate in a survey on health status. Trained investigators administered a structured questionnaire that included demographic characteristics, self-reported symptoms of illness in the last six months before the survey, mental health, and history of COVID-19. Findings: Unadjusted regression estimates indicated positive correlations between symptomatic complaints and COVID-19 exposure, suggesting lingering effects of COVID-19 in this population. The overall physical morbidity index was higher among those who tested positive for COVID-19, as was the incidence of new cases. However, both morbidity and incidence became statistically insignificant after adjustment for multiple comparisons. Cough emerged as the only statistically significant individual persistent symptom. Sex-stratified analyses indicated significant estimates only for physical morbidity in women. Interpretation: This study is one of the first from India that uses a large population-based sample to examine longer term repercussions of COVID infections. The burden of long COVID should primarily be addressed in clinical settings, where specialised treatment for individual cases continues to evolve. Our analyses also provide insight into the size and nature of studies required to assess the population-level burden of long COVID. Funding: This paper was produced under the auspices of the Lancet COVID 19 Commission India Task Force, which was supported financially by the Reliance Foundation. The Lancet COVID 19 Commission was set up in July 2020 and submitted its final report by October 2022. This report by the India Task Force was prepared during the same period.

IntroductionIndia 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.MethodsAn 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.ResultsIt 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.DiscussionThe 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.

Summary: Background: NVX-CoV2373, a Covid-19 vaccine was developed in the USA with ∼90% efficacy. The same vaccine is manufactured in India after technology transfer (called as SII-NVX-CoV2373), was evaluated in this phase 2/3 immuno-bridging study. Methods: This was an observer-blind, randomised, phase 2/3 study in 1600 adults. In phase 2, 200 participants were randomized 3:1 to SII-NVX-CoV2373 or placebo. In phase 3, 1400 participants were randomized 3:1 to SII-NVX-CoV2373 or NVX-CoV2373 (940 safety cohort and 460 immunogenicity cohort). Two doses of study products (SII-NVX-CoV2373, NVX-CoV2373 or placebo) were given 3 weeks apart. Primary objectives were to demonstrate non-inferiority of SII-NVX-CoV2373 to NVX-CoV2373 in terms of geometric mean ELISA units (GMEU) ratio of anti-S IgG antibodies 14 days after the second dose (day 36) and to determine the incidence of causally related serious adverse events (SAEs) through 180 days after the first dose. Anti-S IgG response was assessed using an Enzyme-Linked Immunosorbent Assay (ELISA) and neutralizing antibodies (nAb) were assessed by a microneutralization assay using wild type SARS CoV-2 in participants from the immunogenicity cohort at baseline, day 22, day 36 and day 180. Cell mediated immune (CMI) response was assessed in a subset of 28 participants from immunogenicity cohort by ELISpot assay at baseline, day 36 and day 180. The total follow-up was for 6 months. Trial registration: CTRI/2021/02/031554. Findings: Total 1596 participants (200 in Phase 2 and 1396 in Phase 3) received the first dose. SII-NVX-CoV2373 was found non-inferior to NVX-CoV2373 (anti-S IgG antibodies GMEU ratio 0.91; 95% CI: 0.79, 1.06). At day 36, there was more than 58-fold rise in anti-S IgG and nAb titers compared to baseline in both the groups. On day 180 visit, these antibody titers declined to levels slightly lower than those after the first dose (13–22 fold-rise above baseline). Incidence of unsolicited and solicited AEs was similar between the SII-NVX-CoV2373 and NVX-CoV2373 groups. No adverse event of special interest (AESI) was reported. No causally related SAE was reported. Interpretation: SII-NVX-CoV2373 induced a non-inferior immune response compared to NVX-CoV2373 and has acceptable safety profile. Funding: SIIPL, Indian Council of Medical Research, Novavax.

BackgroundHIV-1 Viral load (VL) measures efficiency of the antiretroviral therapy (ART) after treatment initiation and helps to diagnose virological failures at an early stage. Current VL assays require sophisticated laboratory facilities. As well as there are other challenges pertaining to insufficient laboratory access, cold-chain management and sample transportation. Hence the number of HIV-1 VL testing laboratories is inadequate in the resource limited settings. The revised national tuberculosis elimination programme (NTEP) in India has developed a vast network of point of care (PoC) testing facilities for diagnosis of tuberculosis and several GeneXpert platforms are functional under this programme. Both the GeneXpert HIV-1 assay and HIV-1 Abbott real time assay are comparable and GeneXpert HIV-1 assay can be used as PoC for HIV-1 Viral load testing. Also, the dried blood spot (DBS) as a sample type has been considered as a good option for HIV-1 VL testing in hard to reach areas. This protocol is therefore developed to assess the feasibility of integrating HIV-1 VL testing among people living with HIV (PLHIV) attending ART centres using the two public health models under the current programme: 1. HIV-1 VL testing using GeneXpert platform and plasma as a sample type, and 2. HIV-1 VL testing using Abbott m2000 platform and DBS as a sample type.MethodsThis ethically approved feasibility study will be implemented at two moderate to high burden ART centres where VL testing facility is not available in the town. Under Model-1, arrangements will be made to carry out VL testing on the adjacent GeneXpert facility and under Model-2, DBS will be prepared on site and couriered to identified viral load testing laboratories. In order to assess the feasibility, data will be collected on pretested questionnaire pertaining to number of samples tested for VL testing, number of samples tested for tuberculosis (TB) diagnosis and the turnaround time (TAT). In-depth interviews will be conducted among the service providers at ART centre and different laboratories for addressing any issues regarding the model implementation.ResultsThe proportion of PLHIV tested for VL at ART centres, total TAT for both models including TAT for sample transportation, sample testing and receipt of results as well as proportion of sample rejections and reasons for the same, correlation coefficient between DBS based and plasma based VL testing will be estimated using various statistical tools.ConclusionIf found promising, these public health approaches will be helpful for the policy makers and program implementation in scaling up HIV-1 viral load testing within India.

Background The Joint United Nations Programme on AIDS (UNAIDS) has emphasized on the incidence-prevalence ratio (IPR) and incidence-mortality ratio (IMR) to measure the progress in HIV epidemic control. In this paper, we describe the status of epidemic control in India and in various states in terms of UNAIDS’s recommended metrices. Method The National AIDS Control Programme (NACP) of India spearheads work on mathematical modelling to estimate HIV burden based on periodically conducted sentinel surveillance for providing guidance to program implementation and policymaking. Using the results of the latest round of HIV Estimations in 2019, IPR and IMR were calculated. Results National level IPR was 0.029 [0.022–0.037] in 2019 and ranged from 0.01 to 0.15 in various States and Union Territories (UTs). Corresponding Incidence-Mortality Ratio was at 0.881 [0.754–1.014] nationally and ranged between 0.20 and 12.90 across the States/UTs. Conclusions Based on UNAIDS recommended indicators for HIV epidemic control, namely IPR and IMR; national AIDS response in India appears on track. However, the program success is not uniform and significant heterogeneity as well as expanding epidemic was observed at the level of States or UTs. Reinforcing States/UTs specific and focused HIV prevention, testing and treatment initiatives may help in the attainment of 2030 Sustainable Development Goals of ending AIDS as a public health threat by 2030.