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.

IMPACT of TENOFOVIR on SARS-CoV-2 INFECTION among PEOPLE LIVING with HIV

Background: The impact of some antiretrovirals against SARS-CoV-2 infection and disease severity is conflicting. We evaluated the effect of tenofovir alafenamide/emtricitabine (TAF/FTC) and tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) against SARS-CoV-2 infection and associated clinical outcomes among people living with (PLWH). Methods: We conducted a propensity score-matched analysis leveraging data from the PISCIS cohort of PLWH in Catalonia (Spain). We matched for TAF/FTC versus ABC/3TC in a ratio of 1:1, and 1:3 for TDF/FTC versus ABC/3TC, and TDF/FTC versus TAF/FTC. We used logistic regression to assess the association between tenofovir-based ART and SARS-CoV-2 diagnosis and associated hospitalisation. Results: In our entire cohort [median age: 46.1 years, 82.3% males], 7550 PLWH were being treated with TAF/FTC, 1020 receiving TDF/FTC, and 4135 receiving ABC/3TC. After propensity score-matching, SARS-CoV-2 diagnosis rates were the same in TAF/FTC versus ABC/3TC recipients (12.2% vs 12.2%, P=1.00);lower among TDF/FTC versus ABC/3TC recipients (9.7% vs 12.4%, P=0.05) with borderline significance;and lower among TDF/FTC versus TAF/FTC recipients (9.7% vs 12.6%, P=0.03). In well-adjusted logistic regression models, TAF/FTC was not associated with reduced SARS-CoV-2 diagnosis (adjusted odds ratio [aOR] 0.97;95% confidence interval [CI], 0.83-1.12) or associated hospitalisation (aOR 0.95;95% CI, 0.62-1.45). TDF/FTC compared to ABC/3TC, was not associated with reduced SARS-CoV-2 diagnosis (aOR 0.81;95% CI, 0.61-1.07) or hospitalisation (aOR 0.49;95% CI, 0.14-1.27). TDF/FTC was not associated with reduced SARS-CoV-2 diagnosis (aOR 0.81;95% CI, 0.61-1.07) or associated hospitalisation (aOR 0.47;95% CI, 0.14-1.22) compared to TAF/FTC. Conclusion: TAF/FTC or TDF/FTC were not associated with reduced SARS-CoV-2 diagnosis rates or associated hospitalisations among PLWH. TDF/FTC users had baseline characteristics intrinsically associated with more benign SARS-CoV-2 infection outcomes. Tenofovir exposure or not should not modify the preventive or therapeutic SARS-CoV-2 infection management.

IMPACT of COVID OUTBREAK on PREVENTION and CARE for HIV and STIs at A LARGE HOSPITAL

Background: Routine medical care was drastically affected by the overwhelming irruption of COVID-19 pandemic. We comprehensively assessed the impact of the COVID-19 pandemic on the prevention and care for HIV and other sexually transmitted infections at a large reference hospital providing preventive and clinical services for HIV infection and other sexually transmitted infections. Methods: We retrospectively compared clinical and laboratory data from March to December 2020 (first ten months of the SARS-CoV-2 epidemics in Spain) vs. the same period 2019 in the setting of Hospital Clínic of Barcelona which provides preventive and clinical services for HIV infection and other sexually transmitted infections for the region of Catalonia and is the largest of its kind in Spain. Monthly clinical data on HIV pre-exposure and post-exposure prophylaxis users and on adults with HIV infection were retrieved from the administrative hospital database. Monthly tests for HIV, hepatitis B and C, Treponema pallidum, Neisseria gonorrhoeae, and Chlamydia trachomatis, and plasma lipids and glucose were recovered from the laboratory database. De novo HIV, hepatitis B, or hepatitis C diagnosis were considered whenever a person had a first known positive laboratory test. Results: There were less (28% reduction) but more advanced (mean [SD] CD4 cell counts per mm3 at HIV diagnosis 305 [167] vs. 370 [170], P<0.001;26 (18%) persons had AIDS-defining conditions at HIV diagnosis vs. 20 (10%), P=0.03) HIV cases and more gonorrhea (39% increase, P<0.001) and chlamydia (37% increase, P<0.001) infections in 2020 vs. 2019. In people with HIV, rates of viral load above the level of detection remained stable (11% vs 11%, P=0.147) despite less scheduled visits (25% reduction, P<0.001). However, they had less antiretroviral prescription changes (10% reduction, P=0.018), worse plasma lipids (mean total cholesterol 190 vs 185 mg/dL, P<0.001;mean LDL cholesterol 114 vs 110 mg/dL, P<0.001;mean triglycerides 136 vs 125 mg/dL, P<0.001;mean HDL cholesterol 47 vs 48 mg/dL, P=0.006), and an excess of mortality (29 deaths vs 11, 264% increase, P=0.006) due in great part to COVID-19 (n=11) but also to other non-COVID-19 causes. Conclusion: In the setting of a large Spanish reference hospital, SARS-CoV-2 epidemics was associated with an increase of some prevalent sexually transmitted infections, with less but more advanced de novo HIV infections, and with worse non-virologic healthcare outcomes and higher mortality in people living with HIV.

HIV and SARS-CoV-2 Co-infection: Epidemiological, Clinical Features, and Future Implications for Clinical Care and Public Health for People Living with HIV (PLWH) and HIV Most-at-Risk Groups.

PURPOSE OF REVIEW: The purpose of this review is to use the currently available clinical and epidemiological data, to identify key aspects to improve both the clinical management and public health response to SARS-CoV-2/HIV co-infection among HIV vulnerable populations and people living with HIV (PLWH). RECENT FINDINGS: While at the beginning of the COVID-19 pandemic, the lack of robust information on SARS-CoV-2/HIV co-infection, prevented a clear picture of the synergies between them, currently available data strongly support the importance of common structural factors on both the acquisition and clinical impact of these infections and the relevance of age, comorbidities, and detectable HIV viral load as associated worse prognostic factors among PLWH. Although more information is needed to better understand the biological, clinical, and epidemiological relationship between both infections, a syndemic approach to prevent SARS-CoV-2 among HIV high-risk groups and PLWH, targeting these populations for SARS-CoV-2 vaccines and protocolizing early identification of PLWH with worse COVID-19 prognosis factors, is crucial strategies to decrease the overall impact of SARS-CoV-2 /HIV co-infection.

COVID-19: from epidemiology to treatment.

The COVID-19 pandemic has greatly impacted the daily clinical practice of cardiologists and cardiovascular surgeons. Preparedness of health workers and health services is crucial to tackle the enormous challenge posed by SARS-CoV-2 in wards, operating theatres, intensive care units, and interventionist laboratories. This Clinical Review provides an overview of COVID-19 and focuses on relevant aspects on prevention and management for specialists within the cardiovascular field.