Capacity Building in Sub-Saharan Africa as Part of the INTENSE-TBM Project During the COVID-19 Pandemic.

Tuberculous meningitis (TBM) is the most severe and disabling form of tuberculosis (TB), with at least 100,000 cases per year and a mortality rate of up to 50% in individuals co-infected with human immunodeficiency virus type 1 (HIV-1). To evaluate the efficacy and safety of an intensified anti-tubercular regimen and an anti-inflammatory treatment, the INTENSE-TBM project includes a phase III randomised clinical trial (TBM-RCT) in four countries in sub-Saharan Africa (SSA). Within this framework, we designed a comprehensive capacity-building work package ensuring all centres had, or would acquire, the ability to conduct the TBM-RCT and developing a network of skilled researchers, clinical centres and microbiology laboratories. Here, we describe these activities, identify strengths/challenges and share tools adaptable to other projects, particularly in low- and lower-middle income countries with heterogeneous settings and during the coronavirus disease 2019 (COVID-19) pandemic. Despite major challenges, TBM-RCT initiation was achieved in all sites, promoting enhanced local healthcare systems and encouraging further clinical research in SSA. In terms of certified trainings, the achievement levels were 95% (124/131) for good clinical practice, 91% (39/43) for good clinical laboratory practice and 91% (48/53) for infection prevention and control. Platform-based research, developed as part of capacity-building activities for specific projects, may be a valuable tool in fighting future infectious diseases and in developing high-level research in Africa.

The INTENSE-TBM project aimed to design a comprehensive work-package on capacity building, ensuring all centres would acquire the ability to conduct a phase III randomised clinical trial on TBM in sub-Saharan Africa, to reduce tuberculous meningitis mortality and morbidity in patients with/without HIV-1 co-infection. Therefore, the INTENSE-TBM project is an example of how an international clinical research consortium can provide opportunities to enhance local capacity building and promote centres without previous experience in clinical research. This article provides practical approaches for implementing effective capacity-building programmes. We highlight how to overcome limitations imposed by the COVID-19 pandemic to successfully complete clinics, laboratory set-ups and personnel training, so as to optimise resources and empower African institutions on a local level. At the same time, our experience shows how capacity-building programmes can deliver long-lasting impact that extends beyond the original aims of the project (e.g. HIV and TB), and support local health systems in fighting other infectious disease (e.g. COVID-19). Research projects in low- and lower-middle income countries with heterogeneous settings could stand to benefit the most.

SARS-CoV-2 VACCINATION: IMPACT on HIV-1 RNA LEVELS and ANTIBODY RESPONSE among PLWH

Background: The immunogenicity and safety of mRNA-based vaccination in people living with HIV have yet to be clarified. We aimed to describe the impact of SARS-CoV-2 mRNA vaccination on safety, HIV-RNA control, and humoral immune responses after two doses of vaccine. Methods: From January 2021 to April 2021, vaccination with mRNA1273 (Moderna) and BNT162b2 (BioNTech/Pfizer) was offered to every individual with HIV registered at our institution who fulfilled vaccination criteria and consented to routine vaccination. HIV-1 RNA levels and anti-SARS-CoV-2 S total Ig (Elecsys®, Roche Diagnostics, Rotkreuz, Switzerland) were measured at the time of the first and second doses, 30 days later, and at 6 months after the first dose. Results: The study sample included 131 individuals (median age: 54 years [interquartile range (IQR): 47-60.5]);male: 70.2%;median baseline CD4-T cell: 602 cells/μ l [IQR: 445.0-825.5]). HIV viral load data were collected for 129 patients at the time of the first dose (M0) and 30 days later (M1);for 124 patients, 30 days after the second dose (M2);and for 42 patients, 6 months after the first dose (M6). Twenty (15.5%) of 129 patients had detectable HIV-1 RNA (>20 copies/ml;IQR: 24.0-43.5) at M0, 13/129 (10.1%) at M1 (among which 5 were newly detected), 15/124 (12.1%) at M2 (among which 4 were newly detected), and 6/42 (14.3%) at M6. HIV-RNA levels returned below the detection threshold of 20 copies/mL at the subsequent measure. All analyzed patients showed a positive anti-SARS-CoV-2 S Ig after vaccination with geometric mean titers (GMT) of 131.8 U/ml (95% CI: 130.4-133.2) 30 days after the first dose and 2003.4 U/ml (95% CI: 2002.3-2004.4) 30 days after the second dose. Six months after the first dose, 75/131 patients were analyzed, and they were all still positive for anti-SARS-CoV-2 S Ig, with GMT of 1132.2 U/ml (95% CI: 1131.0-1133.4). We found no statistical significance in anti-SARS-CoV-2 S Ig titers between patients with detectable and undetectable HIV-1 RNA. No serious adverse effects were reported. Conclusion: In a patient population on effective antiretroviral drugs, only minor or transient effects of mRNA vaccines on HIV-1 RNA levels were observed. All patients developed anti-SARS-CoV-2 S total antibodies after two-dose vaccination and antibodies were detectable in all analyzed patients 6 months after the first dose.

HIV in the time of COVID-19 : the meeting between two pandemics

The current COVID-19 pandemic is the main topic of news worldwide by its magnitude and consequences across the entire planet. From a medical point of view, several risk factors for developing severe illness have been reported in the literature, notably an immunosuppressed status. For people living with HIV, several questions have been raised concerning not only their vulnerability, but also in relation to an eventual protection conferred by antiretroviral therapy. This article will address these two pandemics by looking at the potential impact of SARS-CoV-2 on people living with HIV and, in parallel, exploring similarities and differences in terms of treatment, potential for recovery, prevention and their impact on clinical research. We review also future novel therapies for the treatment of HIV. La pandémie de Covid-19 est le sujet d’actualité mondial tant par son ampleur que par ses immenses conséquences. Du point de vue médical, plusieurs facteurs de risque de développer une maladie sévère ont été établis dans la littérature, et l’immunosuppression en fait partie. Concernant les personnes vivant avec le VIH, plusieurs questions se sont posées : sont-elles plus vulnérables à l’acquisition de SARS-CoV-2, ou à une maladie Covid-19 sévère ? Ou au contraire sont-elles protégées par les antirétroviraux ? Cet article aborde ces deux pandémies et recherche des similitudes et des différences en termes de traitement, de guérison, de prévention et de recherche clinique. Nous décrivons brièvement quelques-uns des traitements antirétroviraux les plus innovants.