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Abstract Background Direct-acting antivirals (DAAs) are highly effective in achieving sustained virologic response among those with chronic hepatitis C virus (HCV) infection. Quality of life (QOL) benefits for an HCV-infected population with high numbers of people who inject drugs and people living with HIV (PLHIV) in Eastern Europe have not been explored. We estimated such benefits for Ukraine. Methods Using data from a demonstration study of 12-week DAA conducted in Kyiv, we compared self-reported QOL as captured with the MOS-SF20 at study entry and 12 weeks after treatment completion (week 24). We calculated domain scores for health perception, physical, role and social functioning, mental health and pain to at entry and week 24, stratified by HIV status. Results Among the 857 patients included in the final analysis, health perception was the domain that showed the largest change, with an improvement of 85.7% between entry and week 24. The improvement was larger among those who were HIV negative (104.4%) than among those living with HIV (69.9%). Other domains that showed significant and meaningful improvements were physical functioning, which improved from 80.5 (95% CI 78.9–82.1) at study entry to 89.4 (88.1–90.7) at 24 weeks, role functioning (64.5 [62.3–66.8] to 86.5 [84.9–88.2]), social functioning (74.2 [72.1–76.2] to 84.8 [83.2–86.5]) and bodily pain (70.1 [68.2–72.0] to 89.8 [88.5–91.1]). Across all domains, QOL improvements among PLHIV were more modest than among HIV-negative participants. Conclusion QOL improved substantially across all domains between study entry and week 24. Changes over the study period were smaller among PLHIV.

Background. South Africa (SA) has one of the world’s largest HIV treatment programmes, to which a dramatic increase in life expectancy has been attributed. However, there continue to be concerns regarding the reporting of HIV-related mortality in SA, which varies by source. As accurate HIV mortality estimates are key to measuring the success of the national programme as well as identifying areas for improvement, we propose a complementary approach to monitoring changes in HIV-related mortality using routine inpatient records to examine trends in causes of death and HIV status over time.Objectives. To investigate the feasibility of this approach by calculating mortality due to natural causes in the medical ward of a hospital during 2010 by HIV status.Methods. We conducted a cross-sectional study of inpatient mortality at a regional hospital in Johannesburg, SA, analysing all deaths due to natural causes among adult medical ward inpatients. Cause of death was recorded from the mortuary register. HIV status was ascertained directly from the mortuary register or from laboratory tests specific for HIV diagnosis or monitoring.Results. Of 1 167 inpatients who died, the majority were HIV-positive (58%). HIV positivity among males (55%) was slightly lower than that among females (61%), and HIV-positive patients were younger (median 40 years) than those who were HIV-negative (56 years) and of unknown HIV status (68 years). ‘Infections and parasites’ was the most common cause of natural death (29%). On average, HIV-positive patients were admitted for slightly longer (mean 10.5 days) than HIV-negative patients (9.6 days) and those of unknown HIV status (8.9 days), yet HIV-positive inpatient deaths accounted for the majority (62%) of the total bed days.Conclusions. Even with widespread access to antiretroviral therapy, the majority of inpatient natural deaths at a large public sector hospital in 2010 were of HIV-positive patients and were probably related to HIV. In view of the importance of accurate data on causes of death, both for the HIV programme and to track other diseases, large-scale expansion of this approach over a longer period should be considered.Â

In South Africa, abacavir (ABC) is currently recommended as part of first- and second-line antiretroviral therapy (ART) for HIV-positive paediatric patients. Concerns about overprescribing of the drug, particularly to adults, led to an analysis of ABC use in public sector ART programmes. We investigated current prescription of the drug to adults and children accessing ART in 4 public sector programmes across Gauteng Province, South Africa. ABC was almost exclusively prescribed to children initiating ART and adults requiring regimen changes due to drug toxicities. Patterns of ABC use among HIV-positive paediatric patients followed national ART treatment guidelines on the application of the drug. Although ABC is commonly used in the private sector for adults, the current national ART treatment guidelines for adults and adolescents should include ABC as an alternative to standard first- or second-line ART.

Background. In 2004 the World Health Organization (WHO) released the Interim Policy on Collaborative TB/HIV activities. According to the policy, for people living with HIV (PLWH), activities include intensified case finding, isoniazid preventive therapy (IPT) and infection control. For TB patients, activities included HIV counselling and testing (HCT), prevention messages, and cotrimoxazole preventive therapy (CPT), care and support, and antiretroviral therapy (ART) for those with HIV-associated TB. While important progress has been made in implementation, targets of the WHO Global Plan to Stop TB have not been reached. Objective. To quantify TB/HIV integration at 3 primary healthcare clinics in Johannesburg, South Africa. Methods. Routinely collected TB and HIV data from the HCT register, TB ‘suspect’ register, TB treatment register, clinic files and HIV electronic database, collected over a 3-month period, were reviewed. Results. Of 1 104 people receiving HCT: 306 (28%) were HIV-positive; a CD4 count was documented for 57%; and few received TB screening or IPT. In clinic encounters among PLWH, 921 (15%) had documented TB symptoms; only 10% were assessed by smear microscopy, and few asymptomatic PLWH were offered IPT. Infection control was poorly documented and implemented. HIV status was documented for 155 (75%) of the 208 TB patients; 90% were HIV-positive and 88% had a documented CD4 count. Provision of CPT and ART was poorly documented. Conclusion. The coverage of most TB/HIV collaborative activities was below Global Plan targets. The lack of standardised recording tools and incomplete documentation impeded assessment at facility level and limited the accuracy of compiled data.

Biobanks are repositories that store human biological materials and their associated data. They are rapidly becoming part of national and international networks and give rise to unique ethico-regulatory issues. Whether consent is informed and whether this term should be used when specimens are collected for biobank research is questionable. Where risks occur, they are usually social and relate to identifiability. Public trust and confidence are important for the success of this type of research. Consensus is growing that governance of biobanks should be harmonised. Controlled specimen and data access agreements are essential. The South African National Health Act (NHA) and its Regulations, that provide the foundation for the legal framework with regard to human tissue and research in South Africa, are silent on the issue of biobanks and the law lags behind while science and technology advance rapidly. The use of biobank assets will lead to significant benefits in human health and should be encouraged while taking account of the associated ethical, legal and social issues and working towards a balance between these two positions.

Background. To date, there are no immunological data for the SARS-CoV-2 heterologous vaccination schedule in the South African (SA) population. Objectives. To assess and compare the immunogenicity and reactogenicity of the Jansen Ad26.COV2.S vaccine with the Pfizer/BioNTechBNT162b2 booster following prime Ad26.COV2.S in 65 SA healthcare workers. Methods. In a prospective, quantitative, cross-sectional trial on individuals >18 years of age vaccinated with a single Ad26.COV2.S dose or single Ad26.COV2.S and a BNT162b2 single-dose/both doses booster, participants filled in a questionnaire on their demographics, type of vaccination, breakthrough infection/s (BTI/s), vaccine reactogenicity, prior SARS-CoV-2 infection and dates of vaccination. Qualitative analysis for presence/absence of anti-S (spike) immunoglobulin G (IgG) was performed using the Euroimmun anti-IgG enzyme-linked immunoassay kit, and anti-S IgG titres were quantitatively assessed using the Abbott IgG Quant II kit. Results. Between 28 October 2021 and 30 November 2021, 65 individuals were enrolled and assigned as either prime Ad26.COV2.S (n=18) or Ad26.COV2.S with a BNT162b2 supplement (n=47) at Charlotte Maxeke Johannesburg Academic Hospital, SA (mean age 45 years (95% confidence interval (CI) 29.5 - 58), 42 women (64.6%) and 23 men (35.4%)). The median IgG titre for the primed Ad26.COV2.S group was 4 272.55 (95% CI 68.40 - 10 351.40) and that for the BNT162b2 supplement group was 7 360.80 (95% CI 4 207.40 - 15 372.60). In the univariate model, the BNT162b2 supplement group showed a significant 1.99 times higher antibody titre factor (95% CI 0.045 - 5.553; p0.05) with antibody titres in both groups. However, sex (–55.381 (95% CI –76.984 - –13.498; p=0.018) in a multivariate model was found to have a statistically significant association with anti-S IgG titres observed in both groups. Participants who received their first dose of BNT162b2 9 - 10 months after their prime Ad26.COV2.S (n=44) had a higher degree of antibody response than those who received it earlier. Reactogenicity was observed to be manageable, with mild/moderate adverse effects in the study population. Conclusion. A BNT162b2 supplement given in single or two doses as booster in individuals primed with Ad26.COV2.S induced immunological response, with acceptable and manageable reactogenicity. This study provides novel evidence of the highest degree of antibody response in individuals who received a BNT162b2 first dose 9 - 10 months after prime Ad26.COV2.S, implying that a longer time gap between the two vaccines stimulates higher antibody response than a shorter gap, and that this antibody response can persist for as long as 6 months after the last BNT162b2 dose.

Background: Developing countries experience limited access to HCV laboratory tests for different reasons. Providing near to real-time HCV testing and results especially to at-risk populations including those in rural settings for timely initiation to treatment is key. Within a rural Myanmar setting, we compared HCV diagnostic detection and quantification of the GeneXpert, and Advanced Biological Laboratories UltraGene-HCV assays against the gold standard and reference method Roche real-time HCV in Myanmar., Methods: Blood samples from 158 high-risk individuals were assessed using three different methods at baseline. Results were checked for normality and log transformed. Log differences and bias between methods were calculated and correlated. Pearson's correlation coefficient was used to determine the association of HCV viral loads across all methods. The level of agreement with the standard method (Roche real time HCV) was assessed using Bland-Altman analyses., Results: There was a strong positive correlation coefficient between all three methods with GeneXpert and Roche having the strongest, r = 0.96, (p<0.001). Compared to Roche, ABL (mean difference, 95 % limits of agreement; -0.063 and -1.4 to 1.3 Log10IU/mL) and GeneXpert (mean difference, 95 % limits of agreement; -0.28 and -0.7 to 1.8 Log10IU/mL) showed a good level of agreement with the GeneXpert being slightly superior., Conclusion: We demonstrate the excellent performance and no-inferiority, in terms of levels of agreements of both GeneXpert and ABL compared to the Roche platform and supporting the use of the POC assays as alternative a cost-effective methods in HCV detection and diagnosis in developing and low resource settings countries., Competing Interests: Declaration of competing interest All other authors who have taken part in this study have nothing to disclose regarding competing financial or personal interest with respect to the work reported in this manuscript. KWC has received a research grant to the institution from Merck Sharp & Dohme., (Copyright © 2024. Published by Elsevier B.V.)

The Sisonke 2 study provided a homologous boost at least 6 months after administration of the priming dose of Ad26.COV2.S for healthcare workers enrolled on the Sisonke phase 3b implementation study. Safety monitoring was via five reporting sources: (i.) self-report through a web-link; (ii.) paper-based case report forms; (iii.) a toll-free telephonic reporting line; (iv.) healthcare professionals-initiated reports; and (v.) active linkage with National Disease Databases. A total of 2350 adverse events were reported by 2117 of the 240 888 (0.88%) participants enrolled; 1625 of the 2350 reported events are reactogenicity events and 28 adverse events met seriousness criteria. No cases of thrombosis with thrombocytopaenia syndrome were reported; all adverse events including thromboembolic disorders occurred at a rate below the expected population rates apart from one case of Guillain Barre Syndrome and one case of portal vein thrombosis. The Sisonke 2 study demonstrates that two doses of Ad26.COV2.S is safe and well tolerated; and provides a feasible model for national pharmacovigilance strategies for low- and middle-income settings., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: In 2021, the HIV prevalence among South African adults was 18% and more than 2 million people had uncontrolled HIV and, therefore, had increased risk of poor outcomes with SARS-CoV-2 infection. We investigated trends in COVID-19 admissions and factors associated with in-hospital COVID-19 mortality among people living with HIV and people without HIV., Methods: In this analysis of national surveillance data, we linked and analysed data collected between March 5, 2020, and May 28, 2022, from the DATCOV South African national COVID-19 hospital surveillance system, the SARS-CoV-2 case line list, and the Electronic Vaccination Data System. All analyses included patients hospitalised with SARS-CoV-2 with known in-hospital outcomes (ie, who were discharged alive or had died) at the time of data extraction. We used descriptive statistics for admissions and mortality trends. Using post-imputation random-effect multivariable logistic regression models, we compared characteristics and the case fatality ratio of people with HIV and people without HIV. Using modified Poisson regression models, we compared factors associated with mortality among all people with COVID-19 admitted to hospital and factors associated with mortality among people with HIV., Findings: Among 397 082 people with COVID-19 admitted to hospital, 301 407 (75·9%) were discharged alive, 89 565 (22·6%) died, and 6110 (1·5%) had no recorded outcome. 270 737 (68·2%) people with COVID-19 had documented HIV status (22 858 with HIV and 247 879 without). Comparing characteristics of people without HIV and people with HIV in each COVID-19 wave, people with HIV had increased odds of mortality in the D614G (adjusted odds ratio 1·19, 95% CI 1·09-1·29), beta (1·08, 1·01-1·16), delta (1·10, 1·03-1·18), omicron BA.1 and BA.2 (1·71, 1·54-1·90), and omicron BA.4 and BA.5 (1·81, 1·41-2·33) waves. Among all COVID-19 admissions, mortality was lower among people with previous SARS-CoV-2 infection (adjusted incident rate ratio 0·32, 95% CI 0·29-0·34) and with partial (0·93, 0·90-0·96), full (0·70, 0·67-0·73), or boosted (0·50, 0·41-0·62) COVID-19 vaccination. Compared with people without HIV who were unvaccinated, people without HIV who were vaccinated had lower risk of mortality (0·68, 0·65-0·71) but people with HIV who were vaccinated did not have any difference in mortality risk (1·08, 0·96-1·23). In-hospital mortality was higher for people with HIV with CD4 counts less than 200 cells per μL, irrespective of viral load and vaccination status., Interpretation: HIV and immunosuppression might be important risk factors for mortality as COVID-19 becomes endemic., Funding: South African National Institute for Communicable Diseases, the South African National Government, and the United States Agency for International Development., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: In this study, we compared admission incidence risk and the risk of mortality in the Omicron BA.4/BA.5 wave to previous waves., Methods: Data from South Africa's SARS-CoV-2 case linelist, national COVID-19 hospital surveillance system, and Electronic Vaccine Data System were linked and analyzed. Wave periods were defined when the country passed a weekly incidence of 30 cases/100 000 population. In-hospital case fatality ratios (CFRs) during the Delta, Omicron BA.1/BA.2, and Omicron BA.4/BA.5 waves were compared using post-imputation random effect multivariable logistic regression models., Results: The CFR was 25.9% (N = 37 538 of 144 778), 10.9% (N = 6123 of 56 384), and 8.2% (N = 1212 of 14 879) in the Delta, Omicron BA.1/BA.2, and Omicron BA.4/BA.5 waves, respectively. After adjusting for age, sex, race, comorbidities, health sector, and province, compared with the Omicron BA.4/BA.5 wave, patients had higher risk of mortality in the Omicron BA.1/BA.2 wave (adjusted odds ratio [aOR], 1.3; 95% confidence interval [CI]: 1.2-1.4) and Delta wave (aOR, 3.0; 95% CI: 2.8-3.2). Being partially vaccinated (aOR, 0.9; 95% CI: .9-.9), fully vaccinated (aOR, 0.6; 95% CI: .6-.7), and boosted (aOR, 0.4; 95% CI: .4-.5) and having prior laboratory-confirmed infection (aOR, 0.4; 95% CI: .3-.4) were associated with reduced risks of mortality., Conclusions: Overall, admission incidence risk and in-hospital mortality, which had increased progressively in South Africa's first 3 waves, decreased in the fourth Omicron BA.1/BA.2 wave and declined even further in the fifth Omicron BA.4/BA.5 wave. Mortality risk was lower in those with natural infection and vaccination, declining further as the number of vaccine doses increased., Competing Interests: Potential conflicts of interest. S. S. A. K. reports grants or contracts unrelated to this work and paid to institution from the National Institutes of Health, South African Medical Research Council Cooperative Agreement, National Research Foundation/DST, USAID/Right to Care Cooperative agreement, the IQRAA Trust, and EDCTP; an unpaid role as a member of the World Health Organization (WHO) Science Council; a paid role as a member of the Bill and Melinda Gates Foundation (BMGF) Scientific Advisory Committee (meeting honorarium paid to author); and an unpaid role as vice-president of the International Science Council. C. C. reports grants or contracts unrelated to this work and paid to institution from the US Centers for Disease Control and Prevention (CDC), Wellcome Trust, Sanofi Pasteur, PATH, BMGF, and SA-Medical Research Council. A. v. G. reports grants unrelated to this work and paid to institution from the BMGF, Sanofi, CDC, WHO AFRO, Fleming Fund SEQAFRICA, SA MRC, the Solidarity Fund for Innovative Projects, NIH training grant, and ASLM PGI and a role as chair for the National Advisory Group for Immunisation. I. S. reports an institutional grant unrelated to this work from NIH DAIDS–WITS Helen Joseph Hospital CRS. M. J. G. reports grants or contracts unrelated to this work and paid to institution from the South African Medical Research Council and BMGF. N. W. reports grants paid to institution and unrelated to this work from the BMGF, Sanofi, and CDC. R. W. reports shareholding with Adcock Ingram Holdings Ltd, Dischem Pharmacies Ltd, Discovery Ltd, Netcare Ltd, and Aspen Pharmacare Holdings Ltd. S. W. reports grants unrelated to this work and paid to institution from the BMGF, Sanofi, CDC, and Welcome Trust. W. J. reports grants or contracts related to a long coronavirus disease 2019 study, paid to institution, from the BMGF. All remaining authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Dietary patterns and beliefs are influenced by socioeconomic status, cultural influences, as well as medical advice, social media and marketing. Medical doctors are expected to provide correct, updated and non-biased nutritional advice to their patients, but their own dietary behaviors and attitudes may influence nutritional counselling., Methods: We have investigated dietary habits and food attitudes among medical students by using an anonymous survey distributed to all students at the Medical Faculty, University of Bergen, Norway. The survey included a 36-item questionnaire covering information about demographics, former and current diet, use of nutritional supplements, tobacco and alcohol, in addition to food attitudes and nutritional knowledge. Descriptive statistics were calculated for each survey item., Results: Of the 880 students, 394 responded to the survey. Although 90% of the students were omnivores, the majority had a negative attitude towards meat, and considered fish to be healthier than meat. Significantly more women than men reported use of a special diet and excluded meat from their diet, even if they were omnivores. The most frequently used supplement was cod liver oil or omega 3 fatty acids., Conclusion: The medical students' diet and food attitudes not only reflect current health recommendations, but also popular beliefs and marketing in Norway. Curriculum planners should make the students capable of recognizing the influence of social media, marketing and medicine-food industry interactions, to ensure relevant nutrition knowledge for future doctors., (© 2023. The Author(s).)

Objective: To assess the rates of vascular thrombotic adverse events in the first 35 days after one dose of the Ad26.COV2.S vaccine (Janssen/Johnson & Johnson) in healthcare workers in South Africa and to compare these rates with those observed in the general population., Design: Open label, single arm, phase 3B study., Setting: Sisonke study, South Africa, 17 February to 15 June 2021., Participants: The Sisonke cohort of 477 234 healthcare workers, aged ≥18 years, who received one dose of the Ad26.COV2.S vaccine., Main Outcome Measures: Observed rates of venous arterial thromboembolism and vaccine induced immune thrombocytopenia and thrombosis in individuals who were vaccinated, compared with expected rates, based on age and sex specific background rates from the Clinical Practice Research Datalink GOLD database (database of longitudinal routinely collected electronic health records from UK primary care practices using Vision general practice patient management software)., Results: Most of the study participants were women (74.9%) and median age was 42 years (interquartile range 33-51). Twenty nine (30.6 per 100 000 person years, 95% confidence interval 20.5 to 44.0) vascular thrombotic events occurred at a median of 14 days (7-29) after vaccination. Of these 29 participants, 93.1% were women, median age 46 (37-55) years, and 51.7% had comorbidities. The observed to expected ratios for cerebral venous sinus thrombosis with thrombocytopenia and pulmonary embolism with thrombocytopenia were 10.6 (95% confidence interval 0.3 to 58.8) and 1.2 (0.1 to 6.5), respectively. Because of the small number of adverse events and wide confidence intervals, no conclusions were drawn between these estimates and the expected incidence rates in the population., Conclusions: Vaccine induced immune thrombocytopenia and thrombosis after one dose of the Ad26.COV2.S vaccine was found in only a few patients in this South African population of healthcare workers. These findings are reassuring if considered in terms of the beneficial effects of vaccination against covid-19 disease. These data support the continued use of this vaccine, but surveillance is recommended to identify other incidences of venous and arterial thromboembolism and to improve confidence in the data estimates., Trial Registration: ClinicalTrials.gov NCT04838795., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: support from National Treasury of South Africa, National Department of Health, Solidarity Response Fund NPC, Michael and Susan Dell Foundation, Elma Vaccines and Immunisation Foundation, and Bill and Melinda Gates Foundation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Background: Tuberculosis (TB) Trials Consortium Study 31/AIDS Clinical Trials Group A5349, an international randomized open-label phase 3 noninferiority trial showed that a 4-month daily regimen substituting rifapentine for rifampin and moxifloxacin for ethambutol had noninferior efficacy and was safe for the treatment of drug-susceptible pulmonary TB (DS-PTB) compared with the standard 6-month regimen. We explored results among the prespecified subgroup of people with human immunodeficiency virus (HIV) (PWH)., Methods: PWH and CD4+ counts ≥100 cells/μL were eligible if they were receiving or about to initiate efavirenz-based antiretroviral therapy (ART). Primary endpoints of TB disease-free survival 12 months after randomization (efficacy) and ≥ grade 3 adverse events (AEs) on treatment (safety) were compared, using a 6.6% noninferiority margin for efficacy. Randomization was stratified by site, pulmonary cavitation, and HIV status. PWH were enrolled in a staged fashion to support cautious evaluation of drug-drug interactions between rifapentine and efavirenz., Results: A total of 2516 participants from 13 countries in sub-Saharan Africa, Asia, and the Americas were enrolled. Among 194 (8%) microbiologically eligible PWH, the median CD4+ count was 344 cells/μL (interquartile range: 223-455). The rifapentine-moxifloxacin regimen was noninferior to control (absolute difference in unfavorable outcomes -7.4%; 95% confidence interval [CI] -20.8% to 6.0%); the rifapentine regimen was not noninferior to control (+7.5% [95% CI, -7.3% to +22.4%]). Fewer AEs were reported in rifapentine-based regimens (15%) than the control regimen (21%)., Conclusions: In people with HIV-associated DS-PTB with CD4+ counts ≥100 cells/μL on efavirenz-based ART, the 4-month daily rifapentine-moxifloxacin regimen was noninferior to the 6-month control regimen and was safe., Clinical Trials Registration: NCT02410772., Competing Interests: Potential conflicts of interest. The authorship team members have declared any potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Sanofi's commercial interests did not influence the study design; the collection, analysis, or interpretation of data; the preparation of this manuscript; or the decision to submit this manuscript for publication. A Sanofi technical expert served on the protocol team. A. V. reports unpaid participation on 2 advisory boards for a TB trial of high-dose rifampin (InterTB; St George's Hospital, London), and for a trial of shortened treatment for latent TB (McGill University, Montreal) and other financial or nonfinancial interests as part of this trial, Sanofi (Paris, France, and Bridgewater, NJ, USA) donated rifapentine and all other study drugs, supported shipping of study drugs to all sites, and provided funding support for pharmacokinetic testing. From 2007 until 2016, Sanofi donated a total of $2.9 million to the CDC Foundation to supplement CDC funding for rifapentine research; these funds supported prior TBTC studies of rifapentine but were not part of the support for this trial. This information was included in the main study publication (New England Journal of Medicine, 2021). L. M. reports grants or contracts from Merck Sharpe & Dohme Corp (institution received clinical trial fees), Viiv Healthcare (institution received clinical trial fees), Kowa Pharmaceuticals America (pharmaceutical support on protocol), Sanofi-Aventis (pharmaceutical support on protocol), and Adagio Therapeutics, Inc (institution received clinical trial fees). R. M. S. reports grants or contracts from TB Alliance: Drug regimen optimization for new and existing TB drugs, NIH/NIAID: Novel Biomarkers to Shorten TB Treatment, BMGF: TB Drug Lesion Penetration and Translational Modeling, NIH/NIAID/Rutgers: Impact of Pregnancy on Tuberculosis, BMGF/C-Path: In silico assessment of Adaptive Trial Designs, BMGF/DRI: Accelerating evaluation and development of new combination TB drug treatments, UNITAID/SU: Better Evidence and Formulations for Improved MDR-TB Treatment for Children (BENEFIT Kids), NIH/NIAID: Identifying Optimal Treatment Strategies for Tuberculosis, NIH/NIAID/SU: Optimizing and operationalizing pediatric drug-resistant tuberculosis treatment, and BMGF/C-Path: Model-based meta-analysis of endpoints analyzed in Phase III Quinolones clinical trials; including leadership or fiduciary role in other board, society, committee or advocacy group for Leadership and Operations Center (LOC), AIDS Clinical Trials Group (ACTG), WHO working group: Reaching UNGA HLM on TB targets for ending TB in children and adolescents, and Working Group on New TB Drugs (WGND), Core Member. S. S. reports Research contracts with ViiV Healthcare (paid to institution) and participates for NIH DMSB (unpaid participation). R. E. C. reports contract to institution from Unitaid, grant to institution from National Institutes of Health and Novartis, consultant from Johnson & Johnson and spouse is stockholder for Merck. S. E. D. reports support for attending meetings and/or travel from US CDC contract (provided reimbursement of travel expenses to attend the twice-yearly scientific meetings of the CDC TB Trials Consortium.). I. M. S. is the Vice-Chair for ACTG International. P. N. reports a contract from the CDC TB Trials Consortium. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: The Pan-African Consortium for the Evaluation of Anti-Tuberculosis Antibiotics (PanACEA) was designed to build tuberculosis (TB) trial capacity whilst conducting clinical trials on novel and existing agents to shorten and simplify TB treatment. PanACEA has now established a dynamic network of 11 sub-Saharan clinical trial sites and four European research institutions., Objectives: In 2011, a capacity development program, funded by the European & Developing Countries Clinical Trials Partnership (EDCTP), was launched with four objectives, aiming at strengthening collaborating TB research sites to reach the ultimate goal of becoming self-sustainable institutions: networking; training; conducting clinical trials; and infrastructure scaling-up of sites., Methods: Assessment in six sub-Saharan TB-endemic countries (Gabon, Kenya, South Africa, Tanzania, Uganda and Zambia) were performed through a structured questionnaire, site visits, discussion with the PanACEA consortium, setting of milestones and identification of priorities and followed-up with evaluations of each site. The results of this needs-based assessment was then translated into capacity development measures., Results: In the initial phase, over a four-year period (March 2011 - June 2014), the programme scaled-up six sites; conducted a monitoring training program for 11 participants; funded five MSc and four PhD students, fostering gender balance; conducted four epidemiological studies; supported sites to conduct five Phase II studies and formed a sustainable platform for TB research (panacea-tb.net)., Conclusion: Our experience of conducting TB clinical trials within the PanACEA programme environment of mentoring, networking and training has provided a sound platform for establishing future sustainable research centres. Our goal of facilitating emergent clinical TB trial sites to better initiate and lead research activities has been mostly successful., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background and Aim: To demonstrate the use of a standard dose of ledipasvir (LDV) and sofosbuvir (SOF), with or without ribavirin, to treat hepatitis C and hepatitis C/HIV co-infection in Ukraine., Methods: Eligible HCV viraemic adults from two clinics in Kyiv were treated with LDV/SOF with or without weight-based ribavirin for 12 weeks. Clinical assessments were performed at screening and at week 24, and as needed; treatment was dispensed every 4 weeks. The primary outcome was sustained virologic response (SVR) 12 weeks after treatment, with analysis by intention to treat. Cost per patient was estimated in USD (2018) over the 24-week period., Results: Of 868 patients included in the study and initiated on therapy, 482 (55.5%) were co-infected with HIV. The common genotypes were 1 (74.1%) and 3 (22%). Overall, SVR was achieved in 831 of the 868 patients (95.7%). SVR in patients with hepatitis C alone and hepatitis C/HIV co-infection was 98.4% and 93.6%, respectively. Adverse events were infrequent and usually mild. Using generic medication, cost per patient was estimated at US$680., Conclusion: A standard dose of LDV and SOF, with ribavirin as per protocol, resulted in good outcomes for patients with both hepatitis C alone and co-infected with hepatitis C/HIV. Program costs in Ukraine were modest using generic medication., (© 2022 The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Introduction: Voluntary medical male circumcision (VMMC) remains an effective biomedical intervention for HIV prevention in high HIV prevalence countries. In South Africa, United States Agency for International Development VMMC partners provide technical assistance to the Department of Health, at national and provincial levels in support of the establishment of VMMC sites as well as in providing direct VMMC services at site level since April 2012. We describe the outcomes of the Right to Care (RTC) VMMC program implemented in South Africa from 2012 to 2017., Methods: This retrospective study was undertaken at RTC supported facilities across six provinces. Young males aged ≥10 years who presented at these facilities from 1 July 2012 to 31 September 2017 were included. Outcomes were VMMC uptake, HIV testing uptake and rate of adverse events (AEs). Using a de-identified observational database of these clients, summary statistics of the demographic characteristics and outcomes were calculated., Results: There were a total 1,001,226 attendees of which 998,213 (99.7%) were offered VMMC and had a median age of 15 years (IQR = 12-23 years). Of those offered VMMC, 99.6% (994,293) consented, 96.7% (965,370) were circumcised and the majority (46.3%) were from Gauteng province. HIV testing uptake was 71% with a refusal rate of 15%. Of the newly diagnosed HIV positives, 64% (6,371 / 9,972) referrals were made. The rate of AEs, defined as bleeding, infection, and insufficient skin removal) declined from 3.26% in 2012 to 1.17% in 2017. There was a reduction in infection-related AEs from 2,448 of the 2,602 adverse events (94.08%) in 2012 to 129 of the 2,069 adverse events (6.23%) in 2017., Conclusion: There was a high VMMC uptake with a decline in AEs over time. Adolescent men contributed the most to the circumcised population, an indication that the young population accesses medical circumcision more. VMMC programs need to implement innovative demand creation strategies to encourage older males (20-34 years) at higher risk of HIV acquisition to get circumcised for immediate impact in reduction of HIV incidence. HIV prevalence in the total population increased with increasing age, notably in clients above 25 years., Competing Interests: The authors have declared that no competing interests exist.

Background: Direct-acting antivirals (DAAs) are highly effective in achieving sustained virologic response among those with chronic hepatitis C virus (HCV) infection. Quality of life (QOL) benefits for an HCV-infected population with high numbers of people who inject drugs and people living with HIV (PLHIV) in Eastern Europe have not been explored. We estimated such benefits for Ukraine., Methods: Using data from a demonstration study of 12-week DAA conducted in Kyiv, we compared self-reported QOL as captured with the MOS-SF20 at study entry and 12 weeks after treatment completion (week 24). We calculated domain scores for health perception, physical, role and social functioning, mental health and pain to at entry and week 24, stratified by HIV status., Results: Among the 857 patients included in the final analysis, health perception was the domain that showed the largest change, with an improvement of 85.7% between entry and week 24. The improvement was larger among those who were HIV negative (104.4%) than among those living with HIV (69.9%). Other domains that showed significant and meaningful improvements were physical functioning, which improved from 80.5 (95% CI 78.9-82.1) at study entry to 89.4 (88.1-90.7) at 24 weeks, role functioning (64.5 [62.3-66.8] to 86.5 [84.9-88.2]), social functioning (74.2 [72.1-76.2] to 84.8 [83.2-86.5]) and bodily pain (70.1 [68.2-72.0] to 89.8 [88.5-91.1]). Across all domains, QOL improvements among PLHIV were more modest than among HIV-negative participants., Conclusion: QOL improved substantially across all domains between study entry and week 24. Changes over the study period were smaller among PLHIV., (© 2022. The Author(s).)

HIV treatment programs face challenges in identifying patients at risk for loss-to-follow-up and uncontrolled viremia. We applied predictive machine learning algorithms to anonymised, patient-level HIV programmatic data from two districts in South Africa, 2016-2018. We developed patient risk scores for two outcomes: (1) visit attendance ≤ 28 days of the next scheduled clinic visit and (2) suppression of the next HIV viral load (VL). Demographic, clinical, behavioral and laboratory data were investigated in multiple models as predictor variables of attending the next scheduled visit and VL results at the next test. Three classification algorithms (logistical regression, random forest and AdaBoost) were evaluated for building predictive models. Data were randomly sampled on a 70/30 split into a training and test set. The training set included a balanced set of positive and negative examples from which the classification algorithm could learn. The predictor variable data from the unseen test set were given to the model, and each predicted outcome was scored against known outcomes. Finally, we estimated performance metrics for each model in terms of sensitivity, specificity, positive and negative predictive value and area under the curve (AUC). In total, 445,636 patients were included in the retention model and 363,977 in the VL model. The predictive metric (AUC) ranged from 0.69 for attendance at the next scheduled visit to 0.76 for VL suppression, suggesting that the model correctly classified whether a scheduled visit would be attended in 2 of 3 patients and whether the VL result at the next test would be suppressed in approximately 3 of 4 patients. Variables that were important predictors of both outcomes included prior late visits, number of prior VL tests, time since their last visit, number of visits on their current regimen, age, and treatment duration. For retention, the number of visits at the current facility and the details of the next appointment date were also predictors, while for VL suppression, other predictors included the range of the previous VL value. Machine learning can identify HIV patients at risk for disengagement and unsuppressed VL. Predictive modeling can improve the targeting of interventions through differentiated models of care before patients disengage from treatment programmes, increasing cost-effectiveness and improving patient outcomes., (© 2022. The Author(s).)

Background: Real-world evaluation of the safety profile of vaccines after licensure is crucial to accurately characterise safety beyond clinical trials, support continued use, and thereby improve public confidence. The Sisonke study aimed to assess the safety and effectiveness of the Janssen Ad26.COV2.S vaccine among healthcare workers (HCWs) in South Africa. Here, we present the safety data., Methods and Findings: In this open-label phase 3b implementation study among all eligible HCWs in South Africa registered in the national Electronic Vaccination Data System (EVDS), we monitored adverse events (AEs) at vaccination sites through self-reporting triggered by text messages after vaccination, healthcare provider reports, and active case finding. The frequency and incidence rate of non-serious and serious AEs were evaluated from the day of first vaccination (17 February 2021) until 28 days after the final vaccination in the study (15 June 2021). COVID-19 breakthrough infections, hospitalisations, and deaths were ascertained via linkage of the electronic vaccination register with existing national databases. Among 477,234 participants, 10,279 AEs were reported, of which 138 (1.3%) were serious AEs (SAEs) or AEs of special interest. Women reported more AEs than men (2.3% versus 1.6%). AE reports decreased with increasing age (3.2% for age 18-30 years, 2.1% for age 31-45 years, 1.8% for age 46-55 years, and 1.5% for age > 55 years). Participants with previous COVID-19 infection reported slightly more AEs (2.6% versus 2.1%). The most common reactogenicity events were headache (n = 4,923) and body aches (n = 4,483), followed by injection site pain (n = 2,767) and fever (n = 2,731), and most occurred within 48 hours of vaccination. Two cases of thrombosis with thrombocytopenia syndrome and 4 cases of Guillain-Barré Syndrome were reported post-vaccination. Most SAEs and AEs of special interest (n = 138) occurred at lower than the expected population rates. Vascular (n = 37; 39.1/100,000 person-years) and nervous system disorders (n = 31; 31.7/100,000 person-years), immune system disorders (n = 24; 24.3/100,000 person-years), and infections and infestations (n = 19; 20.1/100,000 person-years) were the most common reported SAE categories. A limitation of the study was the single-arm design, with limited routinely collected morbidity comparator data in the study setting., Conclusions: We observed similar patterns of AEs as in phase 3 trials. AEs were mostly expected reactogenicity signs and symptoms. Furthermore, most SAEs occurred below expected rates. The single-dose Ad26.COV2.S vaccine demonstrated an acceptable safety profile, supporting the continued use of this vaccine in this setting., Trial Registration: ClinicalTrials.gov NCT04838795; Pan African Clinical Trials Registry PACTR202102855526180., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: JP received speakers fees from Johnson and Johnson, and spouse is employed by Johnson and Johnson. The other authors have declared that no competing interests exist.

Growing evidence shows that a significant number of patients with COVID-19 experience persistent symptoms, also known as long COVID-19. We sought to identify persistent symptoms of COVID-19 in frontline workers at Right to Care South Africa, who are past the acute phase of illness, using a cross-sectional survey. We analysed data from 207 eligible COVID-19 positive frontline workers who participated in a two-month post-COVID-19 online self-administered survey. The survey response rate was 30%; of the 62 respondents with a median age of 33.5 years (IQR= 30-44 years), 47 (76%) were females. The majority ( n = 55; 88.7%) self-isolated and 7 (11.3%) were admitted to hospital at the time of diagnosis. The most common comorbid condition reported was hypertension, particularly among workers aged 45-55 years. The most reported persistent symptoms were characterised by fatigue, anxiety, difficulty sleeping, chest pain, muscle pain, and brain fog. Long COVID-19 is a serious phenomenon, of which much is still unknown, including its causes, how common it is especially in non-hospitalised healthcare workers, and how to treat it. Given the rise in COVID-19 cases, the prevalence of long COVID-19 is likely to be substantial; thus, the need for rehabilitation programs targeted at each persistent COVID-19 symptom is critical.

Background: We aimed to assess the effectiveness of a single dose of the Ad26.COV2.S vaccine (Johnson & Johnson) in health-care workers in South Africa during two waves of the South African COVID-19 epidemic., Methods: In the single-arm, open-label, phase 3B implementation Sisonke study, health-care workers aged 18 years and older were invited for vaccination at one of 122 vaccination sites nationally. Participants received a single dose of 5 × 10 10 viral particles of the Ad26.COV2.S vaccine. Vaccinated participants were linked with their person-level data from one of two national medical insurance schemes (scheme A and scheme B) and matched for COVID-19 risk with an unvaccinated member of the general population. The primary outcome was vaccine effectiveness against severe COVID-19, defined as COVID-19-related admission to hospital, hospitalisation requiring critical or intensive care, or death, in health-care workers compared with the general population, ascertained 28 days or more after vaccination or matching, up to data cutoff. This study is registered with the South African National Clinical Trial Registry, DOH-27-022021-6844, ClinicalTrials.gov, NCT04838795, and the Pan African Clinical Trials Registry, PACTR202102855526180, and is closed to accrual., Findings: Between Feb 17 and May 17, 2021, 477 102 health-care workers were enrolled and vaccinated, of whom 357 401 (74·9%) were female and 119 701 (25·1%) were male, with a median age of 42·0 years (33·0-51·0). 215 813 vaccinated individuals were matched with 215 813 unvaccinated individuals. As of data cutoff (July 17, 2021), vaccine effectiveness derived from the total matched cohort was 83% (95% CI 75-89) to prevent COVID-19-related deaths, 75% (69-82) to prevent COVID-19-related hospital admissions requiring critical or intensive care, and 67% (62-71) to prevent COVID-19-related hospitalisations. The vaccine effectiveness for all three outcomes were consistent across scheme A and scheme B. The vaccine effectiveness was maintained in older health-care workers and those with comorbidities including HIV infection. During the course of the study, the beta (B.1.351) and then the delta (B.1.617.2) SARS-CoV-2 variants of concerns were dominant, and vaccine effectiveness remained consistent (for scheme A plus B vaccine effectiveness against COVID-19-related hospital admission during beta wave was 62% [95% CI 42-76] and during delta wave was 67% [62-71], and vaccine effectiveness against COVID-19-related death during beta wave was 86% [57-100] and during delta wave was 82% [74-89])., Interpretation: The single-dose Ad26.COV2.S vaccine shows effectiveness against severe COVID-19 disease and COVID-19-related death after vaccination, and against both beta and delta variants, providing real-world evidence for its use globally., Funding: National Treasury of South Africa, the National Department of Health, Solidarity Response Fund NPC, The Michael & Susan Dell Foundation, The Elma Vaccines and Immunization Foundation, and the Bill & Melinda Gates Foundation., Competing Interests: Declaration of interests L-GB declares honoraria for advisory roles from MSD, ViiV Health Care, and Gilead. RJL declares Department of Science and Innovation and South African Medical Research Council (SAMRC) funding to the KwaZulu-Natal Research Innovation and Sequencing Platform at the University of KwaZulu-Natal for the Network for Genomic Surveillance South Africa, which supported the genomic sequencing for this study; and committee membership of the Ministerial Advisory Committee on COVID-19 Vaccines (a committee that makes recommendations to the Minister of South Africa on the national COVID-19 vaccine programme. CC declares grants or contracts from CDC, PATH, the Bill & Melinda Gates Foundation, SAMRC, Wellcome Trust, and Sanofi Pasteur in the past 36 months. MG reports grants from SAMRC during the conduct of the study, and grants from the Bill & Melinda Gates Foundation outside of the submitted work. DBa reports grants from US National Institutes of Health (NIH) and Janssen during the conduct of the study; grants from Defense Advanced Research projects Agency, Massachusetts Consortium on Pathogen Readiness, Ragon Institute, the Bill & Melinda Gates Foundation, SAMRC, Henry Jackson Foundation, Musk Foundation, Gilead, Legend Bio, CureVac, Sanofi, Intima Bio, Alkermes, and Zentalis; and personal fees from SZQ Bio, Pfizer, Celsion, Avidea, Laronde, Meissa, and Vector Sciences outside of the submitted work DBr has three patents (63/121,482; 63/133,969; 63/135,182) licensed to Janssen. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

In late December 2019, pneumonia cases of unknown origin were reported in Wuhan, China. This virus was named SARS-CoV2 and the clinical syndrome was named coronavirus disease 19 (COVID-19). South Africa, despite strict and early lockdown has the highest infection rate in Africa. A key component of South Africa's response to SARSCoV2 was the rapid scale-up of diagnostic testing. The Abbott SARS-CoV2 assay detects IgG antibodies against the Nucleocapsid (N) protein of the SARS-CoV2 virus. This study undertook to validate and evaluate performance criteria of the Abbott assay and to establish whether this assay would show clinical utility in our population. Positive patients (n = 391) and negative controls (n = 139) were included. The Architect-i and Alinity-i systems were analyzers that were used to perform the SARS-CoV-2 IgG assay. In-house ELISA was incorporated into the study as a confirmatory serology test. A total of number of 530 participants was tested, 87% were symptomatic with infection and 13% were asymptomatic. When compared to RT-qPCR, the sensitivity of Architect and Alinity SARS-CoV2 assays was 69.5% and 64.8%, respectively. Specificity for Architect and Alinity assays was 95% and 90.3%, respectively. The Abbott assay was also compared to in house ELISA assay, with sensitivity for the Architect and Alinity assays of 94.7% and 92.5%, respectively. Specificity for Abbott Alinity assays was 91.7% higher than Abbott Architect 88.1%. Based on the current findings testing of IgG after 14 days is recommended in South Africa and supports other studies performed around the world., Competing Interests: The authors have declared that no competing interests exist.

Background: In South Africa (SA), &gt;2.4 million cases of COVID‑19 and &gt;72 000 deaths were recorded between March 2020 and 1 August 2021, affecting the country's 52 districts to various extents. SA has committed to a COVID‑19 vaccine roll-out in three phases, prioritising frontline workers, the elderly, people with comorbidities and essential workers. However, additional actions will be necessary to support efficient allocation and equitable access for vulnerable, access-constrained communities., Objectives: To explore various determinants of disease severity, resurgence risk and accessibility in order to aid an equitable, effective vaccine roll-out for SA that would maximise COVID‑19 epidemic control by reducing the number of COVID‑19 transmissions and resultant deaths, while at the same time reducing the risk of vaccine wastage., Methods: For the 52 districts of SA, 26 COVID‑19 indicators such as hospital admissions, deaths in hospital and mobility were ranked and hierarchically clustered with cases to identify which indicators can be used as indicators for severity or resurgence risk. Districts were then ranked using the estimated COVID‑19 severity and resurgence risk to assist with prioritisation of vaccine roll-out. Urban and rural accessibility were also explored as factors that could limit vaccine roll-out in hard-to-reach communities., Results: Highly populated urban districts showed the most cases. Districts such as Buffalo City, City of Cape Town and Nelson Mandela Bay experienced very severe first and second waves of the pandemic. Districts with high mobility, population size and density were found to be at highest risk of resurgence. In terms of accessibility, we found that 47.2% of the population are within 5 km of a hospital with ≥50 beds, and this percentage ranged from 87.0% in City of Cape Town to 0% in Namakwa district., Conclusions: The end goal is to provide equal distribution of vaccines proportional to district populations, which will provide fair protection. Districts with a high risk of resurgence and severity should be prioritised for vaccine roll-out, particularly the major metropolitan areas. We provide recommendations for allocations of different vaccine types for each district that consider levels of access, numbers of doses and cold-chain storage capability.

Introduction: The International AIDS Society convened a multidisciplinary committee of experts in December 2020 to provide guidance and key considerations for the safe and ethical management of clinical trials involving people living with HIV (PLWH) during the SARS-CoV-2 pandemic. This consultation did not discuss guidance for the design of prevention studies for people at risk of HIV acquisition, nor for the programmatic delivery of antiretroviral therapy (ART)., Discussion: There is strong ambition to continue with HIV research from both PLWH and the research community despite the ongoing SARS-CoV-2 pandemic. How to do this safely and justly remains a critical debate. The SARS-CoV-2 pandemic continues to be highly dynamic. It is expected that with the emergence of effective SARS-CoV-2 prevention and treatment strategies, the risk to PLWH in clinical trials will decline over time. However, with the emergence of more contagious and potentially pathogenic SARS-CoV-2 variants, the effectiveness of current prevention and treatment strategies may be compromised. Uncertainty exists about how equally SARS-CoV-2 prevention and treatment strategies will be available globally, particularly for marginalized populations, many of whom are at high risk of reduced access to ART and/or HIV disease progression. All of these factors must be taken into account when deciding on the feasibility and safety of developing and implementing HIV research., Conclusions: It can be assumed for the foreseeable future that SARS-CoV-2 will persist and continue to pose challenges to conducting clinical research in PLWH. Guidelines regarding how best to implement HIV treatment studies will evolve accordingly. The risks and benefits of performing an HIV clinical trial must be carefully evaluated in the local context on an ongoing basis. With this document, we hope to provide a broad guidance that should remain viable and relevant even as the nature of the pandemic continues to develop., (© 2022 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Sisonke is a multicentre, open-label, single-arm phase 3B vaccine implementation study of healthcare workers (HCWs) in South Africa, with prospective surveillance for 2 years. The primary endpoint is the rate of severe COVID‑19, including hospitalisations and deaths. The  Sisonke study enrolled and vaccinated participants nationally at potential vaccination roll-out sites between 17 February and 26 May 2021. After May 2021, additional HCWs were vaccinated as part of a sub-study at selected clinical research sites. We discuss 10 lessons learnt to strengthen national and global vaccination strategies:(i) consistently advocate for vaccination to reduce public hesitancy; (ii) an electronic vaccination data system (EVDS) is critical; (iii) facilitate access to a choice of vaccination sites, such as religious and community centres, schools, shopping malls and drive-through centres; (iv) let digitally literate people help elderly and marginalised people to register for vaccination; (v) develop clear 'how to' guides for vaccine storage, pharmacy staff and vaccinators; (vi) leverage instant messaging platforms, such as WhatsApp, for quick communication among staff at vaccination centres; (vii) safety is paramount - rapid health assessments are needed at vaccination centres to identify people at high risk of serious adverse events, including anaphylaxis or thrombosis with thrombocytopenia syndrome. Be transparent about adverse events and contextualise vaccination benefits, while acknowledging the small risks; (viii) provide real-time, responsive support to vaccinees post vaccination and implement an accessible national vaccine adverse events surveillance system; (ix) develop efficient systems to monitor and investigate COVID‑19 breakthrough infections; and (x) flexibility and teamwork are essential in vaccination centres across national, provincial and district levels and between public and private sectors.

Background: The Janssen-Ad26.COV2.S vaccine is authorized for use in several countries, with more than 30 million doses administered. Mild and severe allergic adverse events following immunization (AEFI) have been reported., Objective: We sought to detail allergic reactions reported during the Sisonke phase 3B study in South Africa., Methods: A single dose of the Ad26.COV2.S vaccine was administered to 4,77,234 South African health care workers between February 17 and May 17, 2021. Monitoring of adverse events used a combination of passive reporting and active case finding. Telephonic contact was attempted for all adverse events reported as "allergy." Anaphylaxis adjudication was performed using the Brighton Collaboration and National Institute of Allergy and Infectious Disease case definitions., Results: Only 251 (0.052%) patients reported any allergic-type reaction (<1 in 2000), with 4 cases of adjudicated anaphylaxis (Brighton Collaboration level 1, n = 3) (prevalence of 8.4 per million doses). All anaphylaxis cases had a previous history of drug or vaccine-associated anaphylaxis. Cutaneous allergic reactions were the commonest nonanaphylatic reactions and included self-limiting, transient/localized rashes requiring no health care contact (n = 92) or isolated urticaria and/or angioedema (n = 70; median onset, 48 [interquartile range, 11.5-120] hours postvaccination) that necessitated health care contact (81%), antihistamine (63%), and/or systemic/topical corticosteroid (16%). All immediate (including adjudicated anaphylaxis) and most delayed AEFI (65 of 69) cases resolved completely., Conclusions: Allergic AEFI are rare following a single dose of Ad26.COV, with complete resolution in all cases of anaphylaxis. Although rare, isolated, delayed-onset urticaria and/or angioedema was the commonest allergic AEFI requiring treatment, with nearly half occurring in participants without known atopic disease., (© 2021 Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology.)

Serology or antibody tests for COVID-19 are designed to detect antibodies (mainly Immunoglobulin M (IgM) and Immunoglobulin G (IgG) produced in response to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2) infection. In this study, 30 lateral flow immunoassays were tested using serum or plasma from patients with confirmed SARS CoV-2 infection. Negative serological controls were accessed from a well-characterised bank of sera which were stored prior to February 2020. Operational characteristics and ease of use of the assays are reported. 4/30 (13%) of kits (Zheihang Orient Gene COVID-19 IgG/IgM, Genrui Novel Coronavirus (2019-nCoV) IgG/IgM, Biosynex COVID-19 BSS IgG/IgM, Boson Biotech 2019-nCoV IgG/IgM) were recommended for SAHPRA approval based on kit sensitivity. Of these, only the Orientgene was recommended by SAHPRA in August 2020 for use within the approved national testing algorithm while the remaining three received limited authorization for evaluation. All kits evaluated work on the same basic principle of immunochromatography with minor differences noted in the shape and colour of cartridges, the amount of specimen volume required and the test duration. Performance of the lateral flow tests were similar to sensitivities and specificities reported in other studies. The cassettes of the majority of kits evaluated (90%) detected both IgG and IgM. Only 23% of kits evaluated contained all consumables required for point-of-care testing. The study highlights the need for thorough investigation of kits prior to implementation., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) has been identified as the causative agent for causing the clinical syndrome of COVID -19. Accurate detection of SARS-CoV-2 infection is not only important for management of infected individuals but also to break the chain of transmission. South Africa is the current epicenter of SARS-CoV-2 infection in Africa. To optimize the diagnostic algorithm for SARS-CoV-2 in the South African setting, the study aims to evaluate the diagnostic performance of the EUROIMMUN Anti-SARS-CoV-2 assays. This study reported the performance of EUROIMMUN enzyme-linked immunosorbent assay (ELISA) for semi-quantitative detection of IgA and IgG antibodies in serum and plasma samples targeting the recombinant S1 domain of the SARS-CoV-2 spike protein as antigen. Samples were collected from 391 individuals who had tested positive for SARS-CoV-2 and 139 SARS CoV-2 negative controls. Samples were stratified by number of days' post-PCR diagnosis and symptoms. The sensitivity of EUROIMMUN IgG was 64.1% (95% CI: 59.1-69.0%) and 74.3% (95% CI: 69.6-78.6%) for IgA and the specificity was lower for IgA [84.2% (95% CI: 77-89.2%)] than IgG [95.2% (95% CI: 90.8-98.4%)]. The EUROIMMUN Anti-SARS-CoV-2 ELISA Assay sensitivity was higher for IgA but low for IgG and improved for both assays in symptomatic individuals and at later timepoints post PCR diagnosis., Competing Interests: The authors have declared that no competing interests exist.

Background: Rifapentine-based regimens have potent antimycobacterial activity that may allow for a shorter course in patients with drug-susceptible pulmonary tuberculosis., Methods: In an open-label, phase 3, randomized, controlled trial involving persons with newly diagnosed pulmonary tuberculosis from 13 countries, we compared two 4-month rifapentine-based regimens with a standard 6-month regimen consisting of rifampin, isoniazid, pyrazinamide, and ethambutol (control) using a noninferiority margin of 6.6 percentage points. In one 4-month regimen, rifampin was replaced with rifapentine; in the other, rifampin was replaced with rifapentine and ethambutol with moxifloxacin. The primary efficacy outcome was survival free of tuberculosis at 12 months., Results: Among 2516 participants who had undergone randomization, 2343 had a culture positive for Mycobacterium tuberculosis that was not resistant to isoniazid, rifampin, or fluoroquinolones (microbiologically eligible population; 768 in the control group, 791 in the rifapentine-moxifloxacin group, and 784 in the rifapentine group), of whom 194 were coinfected with human immunodeficiency virus and 1703 had cavitation on chest radiography. A total of 2234 participants could be assessed for the primary outcome (assessable population; 726 in the control group, 756 in the rifapentine-moxifloxacin group, and 752 in the rifapentine group). Rifapentine with moxifloxacin was noninferior to the control in the microbiologically eligible population (15.5% vs. 14.6% had an unfavorable outcome; difference, 1.0 percentage point; 95% confidence interval [CI], -2.6 to 4.5) and in the assessable population (11.6% vs. 9.6%; difference, 2.0 percentage points; 95% CI, -1.1 to 5.1). Noninferiority was shown in the secondary and sensitivity analyses. Rifapentine without moxifloxacin was not shown to be noninferior to the control in either population (17.7% vs. 14.6% with an unfavorable outcome in the microbiologically eligible population; difference, 3.0 percentage points [95% CI, -0.6 to 6.6]; and 14.2% vs. 9.6% in the assessable population; difference, 4.4 percentage points [95% CI, 1.2 to 7.7]). Adverse events of grade 3 or higher occurred during the on-treatment period in 19.3% of participants in the control group, 18.8% in the rifapentine-moxifloxacin group, and 14.3% in the rifapentine group., Conclusions: The efficacy of a 4-month rifapentine-based regimen containing moxifloxacin was noninferior to the standard 6-month regimen in the treatment of tuberculosis. (Funded by the Centers for Disease Control and Prevention and others; Study 31/A5349 ClinicalTrials.gov number, NCT02410772.)., (Copyright © 2021 Massachusetts Medical Society.)

Countries such as South Africa have limited intensive care unit (ICU) capacity to handle the expected number of patients with COVID-19 requiring ICU care. Remdesivir can prevent deaths in countries such as South Africa by decreasing the number of days people spend in ICU, therefore freeing up ICU bed capacity., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Facility-based, multimonth dispensing of antiretroviral therapy (ART) for HIV could reduce burdens on patients and providers and improve retention in care. We assessed whether 6-monthly ART dispensing was non-inferior to standard of care and 3-monthly ART dispensing., Methods: We did a pragmatic, cluster-randomised, unblinded, non-inferiority trial (INTERVAL) at 30 health facilities in Malawi and Zambia. Eligible participants were aged 18 years or older, HIV-positive, and were clinically stable on ART. Before randomisation, health facilities (clusters) were matched on the basis of country, ART cohort size, facility type (ie, hospital vs health centre), and region or province. Matched clusters were randomly allocated (1:1:1) to standard of care, 3-monthly ART dispensing, or 6-monthly ART dispensing using a simple random allocation sequence. The primary outcome was retention in care at 12 months, defined as the proportion of patients with less than 60 consecutive days without ART during study follow-up, analysed by intention to treat. A 2·5% margin was used to assess non-inferiority. This study is registered with ClinicalTrials.gov, NCT03101592., Findings: Between May 15, 2017, and April 30, 2018, 9118 participants were randomly assigned, of whom 8719 participants (n=3012, standard of care group; n=2726, 3-monthly ART dispensing group; n=2981, 6-monthly ART dispensing group) had primary outcome data available at 12 months and were included in the primary analysis. The median age of participants was 42·7 years (IQR 36·1-49·9) and 5774 (66·2%) of 8719 were women. The primary outcome was met by 2478 (82·3%) of 3012 participants in the standard of care group, 2356 (86·4%) of 2726 participants in the 3-monthly ART dispensing group, and 2729 (91·5%) of 2981 participants in the 6-monthly ART dispensing group. After adjusting for clustering, for retention in care at 12 months, the 6-monthly ART dispensing group was non-inferior to the standard of care group (percentage-point increase 9·1 [95% CI 0·9-17·2]) and to the 3-monthly ART dispensing group (5·0% [1·0-9·1])., Interpretation: Clinical visits with ART dispensing every 6 months was non-inferior to standard of care and 3-monthly ART dispensing. 6-monthly ART dispensing is a promising strategy for the expansion of ART provision and achievement of HIV treatment targets in resource-constrained settings., Funding: US Agency for International Development., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background : The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has swept the world and poses a significant global threat to lives and livelihoods, with 115 million confirmed cases and at least 2.5 million deaths from Coronavirus disease 2019 (COVID-19) in the first year of the pandemic. Developing tools to measure seroprevalence and understand protective immunity to SARS-CoV-2 is a priority. We aimed to develop a serological assay using plant-derived recombinant viral proteins, which represent important tools in less-resourced settings. Methods : We established an indirect ELISA using the S1 and receptor-binding domain (RBD) portions of the spike protein from SARS-CoV-2, expressed in Nicotiana benthamiana . We measured antibody responses in sera from South African patients ( n = 77) who had tested positive by PCR for SARS-CoV-2. Samples were taken a median of 6 weeks after the diagnosis, and the majority of participants had mild and moderate COVID-19 disease. In addition, we tested the reactivity of pre-pandemic plasma ( n = 58) and compared the performance of our in-house ELISA with a commercial assay. We also determined whether our assay could detect SARS-CoV-2-specific IgG and IgA in saliva. Results: We demonstrate that SARS-CoV-2-specific immunoglobulins are readily detectable using recombinant plant-derived viral proteins, in patients who tested positive for SARS-CoV-2 by PCR. Reactivity to S1 and RBD was detected in 51 (66%) and 48 (62%) of participants, respectively. Notably, we detected 100% of samples identified as having S1-specific antibodies by a validated, high sensitivity commercial ELISA, and optical density (OD) values were strongly and significantly correlated between the two assays. For the pre-pandemic plasma, 1/58 (1.7%) of samples were positive, indicating a high specificity for SARS-CoV-2 in our ELISA. SARS-CoV-2-specific IgG correlated significantly with IgA and IgM responses. Endpoint titers of S1- and RBD-specific immunoglobulins ranged from 1:50 to 1:3,200. S1-specific IgG and IgA were found in saliva samples from convalescent volunteers. Conclusion : We demonstrate that recombinant SARS-CoV-2 proteins produced in plants enable robust detection of SARS-CoV-2 humoral responses. This assay can be used for seroepidemiological studies and to measure the strength and durability of antibody responses to SARS-CoV-2 in infected patients in our setting., Competing Interests: FP and SB are employed by Cape Bio Pharms. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Makatsa, Tincho, Wendoh, Ismail, Nesamari, Pera, de Beer, David, Jugwanth, Gededzha, Mampeule, Sanne, Stevens, Scott, Blackburn, Mayne, Keeton and Burgers.)

Background: Dexamethasone and remdesivir have the potential to reduce coronavirus disease 2019 (COVID)-related mortality or recovery time, but their cost-effectiveness in countries with limited intensive care resources is unknown., Methods: We projected intensive care unit (ICU) needs and capacity from August 2020 to January 2021 using the South African National COVID-19 Epi Model. We assessed the cost-effectiveness of (1) administration of dexamethasone to ventilated patients and remdesivir to nonventilated patients, (2) dexamethasone alone to both nonventilated and ventilated patients, (3) remdesivir to nonventilated patients only, and (4) dexamethasone to ventilated patients only, all relative to a scenario of standard care. We estimated costs from the health care system perspective in 2020 US dollars, deaths averted, and the incremental cost-effectiveness ratios of each scenario., Results: Remdesivir for nonventilated patients and dexamethasone for ventilated patients was estimated to result in 408 (uncertainty range, 229-1891) deaths averted (assuming no efficacy [uncertainty range, 0%-70%] of remdesivir) compared with standard care and to save $15 million. This result was driven by the efficacy of dexamethasone and the reduction of ICU-time required for patients treated with remdesivir. The scenario of dexamethasone alone for nonventilated and ventilated patients requires an additional $159 000 and averts 689 [uncertainty range, 330-1118] deaths, resulting in $231 per death averted, relative to standard care., Conclusions: The use of remdesivir for nonventilated patients and dexamethasone for ventilated patients is likely to be cost-saving compared with standard care by reducing ICU days. Further efforts to improve recovery time with remdesivir and dexamethasone in ICUs could save lives and costs in South Africa., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

The WHO developed a generic 'TB patient cost survey' tool and a standardized approach to assess the direct and indirect costs of TB incurred by patients and their households, estimate the proportion of patients experiencing catastrophic costs, and measure the impact of interventions to reduce patient costs. While the generic tool is a facility-based cross-sectional survey, this standardized approach needs to be adapted for longitudinal studies. A longitudinal approach may overcome some of the limitations of a cross-sectional design and estimate the economic burden of TB more precisely. We describe the process of creating a longitudinal instrument and its application to the TB Sequel study, an ongoing multi-country, multi-center observational cohort study. We adapted the cross-sectional WHO generic TB patient cost survey instrument for the longitudinal study design of TB Sequel and the local context in each study country (South Africa, Mozambique, Tanzania, and The Gambia). The generic instrument was adapted for use at enrollment (start of TB treatment; Day 0) and at 2, 6, 12 and 24 months after enrollment, time points intended to capture costs incurred for diagnosis, during treatment, at the end of treatment, and during long-term follow-up once treatment has been completed. These time points make the adapted version suitable for use in patients with either drug-sensitive or drug-resistant TB. Using the adapted tool provides the opportunity to repeat measures and make comparisons over time, describe changes that extend beyond treatment completion, and link cost survey data to treatment outcomes and post-TB sequelae. Trial registration : ClinicalTrials.gov: NCT032516 August 1196, 2017. Abbreviations : DOTS: Directly observed treatment, short-course; DR-TB: Drug-resistant tuberculosis; MDR-TB: Multi-drug resistant tuberculosis; NTP: National Tuberculosis Programme; TB: Tuberculosis; USD: United States Dollar; WHO: World Health Organization.

Access to hepatitis C virus (HCV) testing and treatment is limited in Myanmar. We assessed an integrated HIV and viral hepatitis testing and HCV treatment strategy. Sofosbuvir/velpatasvir (SOF/VEL) ± weight-based ribavirin for 12 weeks was provided at three treatment sites in Myanmar and sustained virologic response (SVR) assessed at 12 weeks after treatment. Participants co-infected with HBV were treated concurrently with tenofovir. Cost estimates in 2018 USD were made at Yangon and Mandalay using standard micro-costing methods. 803 participants initiated SOF/VEL; 4.8% were lost to follow-up. SVR was achieved in 680/803 (84.6%) by intention-to-treat analysis. SVR amongst people who inject drugs (PWID) was 79.7% (381/497), but 92.5% among PWID on opioid substitution therapy (OST) (74/80), and 97.4% among non-PWID (298/306). Utilizing data from 492 participants, of whom 93% achieved SVR, the estimated average cost of treatment per patient initiated was $1030 (of which 54% were medication costs), with a production cost per successful outcome (SVR) of $1109 and real-world estimate of $1250. High SVR rates were achieved for non-PWID and PWID on OST. However, the estimated average cost of the intervention (under the assumption of no genotype testing and reduced real-world effectiveness) of $1250/patient is unaffordable for a national elimination strategy. Reductions in the cost of antivirals and linkage to social and behavioural health services including substance use disorder treatment to increase retention and adherence to treatment are critical to HCV elimination in this population., (© 2020 The Authors. Journal of Viral Hepatitis published by John Wiley & Sons Ltd.)

Background: Lesotho adopted the test-and-treat approach for HIV treatment in June 2016, which increased antiretroviral treatment (ART) clinic volume. We evaluated community-based vs. facility-based differentiated models of multimonth dispensing of ART among stable HIV-infected adults in Lesotho., Methods: Thirty facilities were randomized to 3 arms, facility 3-monthly ART (3MF) (control), community ART groups (3MC), and 6-monthly community distribution points (6MCD). We estimated risk differences (RDs) between arms using population-averaged generalized estimating equations, controlling for baseline imbalances and specifying for clustering. The primary outcome was retention in ART care by intention-to-treat and virologic suppression as a secondary outcome (ClinicalTrials.gov: NCT03438370)., Results: A total of 5,336 participants were enrolled, with 1898, 1558, and 1880 in 3MF, 3MC, and 6MCD, respectively. Retention in ART care was not different across arms and achieved the prespecified noninferiority limit (-3.25%) between 3MC vs. 3MF (control); 6MCD vs. 3MF; and 6MCD vs. 3MC, adjusted RD = -0.1% [95% confidence interval (CI): -1.6% to 1.5%], adjusted RD = -1.3% (95% CI: -3.0% to 0.5%), and adjusted RD = -1.2% (95% CI: -2.9% to 0.5%), respectively. After 12 months, 98.6% (n = 1503), 98.1% (n = 1126), and 98.3% (n = 1285) were virally load (VL) suppressed in 3MF, 3MC, and 6MCD, respectively. There were no differences in VL between 3MC vs. control and 6MCD vs. control, risk ratio (RR) = 1.00 (95% CI: 0.98 to 1.01) and RR = 1.00 (95% CI: 0.98 to 1.01), respectively., Conclusions: There were no differences in retention and VL suppression for stable HIV-infected participants receiving multimonth dispensing of ART within community-based differentiated models when compared with the facility-based standard-of-care model.