Sisonke phase 3B open-label study: Lessons learnt for national and global vaccination scale-up during epidemics.

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 COVID­19, 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 COVID­19 breakthrough infections; and (x) flexibility and teamwork are essential in vaccination centres across national, provincial and district levels and between public and private sectors.

Antiretroviral therapy initiation during tuberculosis treatment and HIV-RNA and CD4 T-lymphocyte responses.

SETTING: A large human immunodeficiency virus (HIV) clinic in South Africa. OBJECTIVE: To examine the effect of initiating antiretroviral therapy (ART) on CD4 and viral response at different time periods during anti-tuberculosis treatment (<14 days, 15-60 days, or ≥60 days) using prospectively collected clinical data. METHODS: Cohort data analysis for 1499 patients with tuberculosis (TB) and HIV co-infection classified according to timing of ART after the initiation of anti-tuberculosis treatment. RESULTS: In adjusted modified Poisson regression models, CD4 and viral responses showed no significant differences according to timing of ART initiation (failure to increase CD4 by 6 months, <14 days vs. >60 days: RR 1.02, 95%CI 0.85-1.22; 15-60 days vs. >60 days: RR 1.00, 95%CI 0.86-1.15; failure to suppress virus by 6 months, <14 days vs. >60 days: RR 0.98, 95%CI 0.59-1.63; 15-60 days vs. >60 days: RR 0.96, 95%CI 0.66-1.41 and viral rebound at 12 months, 14 days vs. >60 days: RR 1.43, 95%CI 0.50-4.12; 15-60 days vs. >60 days: RR 1.14, 95%CI 0.39-3.34). Similar estimates were found in analysis restricted to patients with severe immunosuppression. CONCLUSION: Concerns over the overlapping impact of anti-tuberculosis treatment with ART on ART response should not be a reason for delaying ART in patients with HIV-associated TB.