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1.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-320589

ABSTRACT

Tenofovir has shown promising evidence of improving COVID-19 clinical outcomes in observational studies, still to be confirmed in clinical trials. Disease severity might be reduced under prophylaxis with the prodrug tenofovir disoproxil fumarate (TDF), while the protection seems to decrease, or even to lack, when using the alternative prodrug tenofovir alafenamide fumarate (TAF).  Aiming to understand why TDF-prophylaxis might reduce COVID-19 severity upon infection we developed a multi-scale analysis framework combining  in vitro  susceptibility data, molecular docking, and within-host dynamics modeling, and using remdesivir–the only antiviral approved to date against COVID-19– as a point of reference.First, our docking model predicted that intracellularly active tenofovir diphosphate binds into the SARS-CoV-2 RNA polymerase in the same site as the antiviral remdesivir triphosphate, but presents lower binding energy, likely reducing the overall inhibition of viral replication and making the antiviral efficacy more susceptible to the drug intracellular concentration. Second, using data from  in vitro  viral   cultures with plausible TDF therapeutic concentrations, we estimated that the drug can inhibit SARS-COV-2 replication at an efficacy ranging between 54-99%  conditional to the viral cycle length. Third, assuming values approximating this range of inhibition for  in vivo  viral replication during human SARS-COV-2 infection, we found that prophylaxis with TDF with high penetration into viral target cells is capable of delaying viral replication, mitigating direct cell damage and allowing time for the host to mount the adaptive immunity. Last, we found that the potential antiviral effect can be substantially reduced when TDF is given after infection begins. Our work provides a potential mechanistic explanation of the observed clinical effect of TDF against SARS-CoV-2 infection. The proposed inference framework can help to optimize the evaluation of antiviral therapies for COVID-19, in particular those targeting the RNA dependent RNA polymerase.

2.
AIDS ; 36(2): 161-168, 2022 02 01.
Article in English | MEDLINE | ID: covidwho-1672442

ABSTRACT

The relative susceptibility of people with HIV (PWH) to Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is debated. Numerous studies have been published with apparently contradictory findings, but comparisons are difficult because they have been conducted in populations with different characteristics (e.g. age, prevalence comorbidities) and have used different comparison groups (e.g. HIV-negative cohorts, coronavirus disease 2019 (COVID-19) hospitalized patients, general population), and because of challenges to measure the most important confounders. Here, we review the evidence regarding risk and severity of SARS-CoV-2 infection in PWH compared with persons without HIV. Publications originate largely from high-income settings where the majority of the PWH are on antiretroviral therapy (ART). Despite early evidence supporting higher frequency of SARS-CoV-2 testing in PWH on ART, HIV infection is not associated with SARS-CoV-2 infection, once confounding by socioeconomic characteristic is taken into account. Most publications identify increased COVID-19 severity in PWH compared with people without HIV from the general population or compared with COVID-19 hospitalized patients. The only study with an adequate comparison group to reduce confounding, has not identified differences in COVID-19 disease severity by HIV. Publications consistently identify that COVID-19 severity in PWH is not homogeneous and increases with age and baseline comorbidities. As PWH have a higher prevalence of comorbidities than people without HIV, examining their respective contribution to poor health outcomes is not straight forward as comorbidities could mediate the effect of HIV on COVID-19 outcomes.


Subject(s)
COVID-19 , HIV Infections , Anti-Retroviral Agents/therapeutic use , COVID-19 Testing , HIV Infections/complications , HIV Infections/drug therapy , Humans , SARS-CoV-2
3.
Curr Opin Infect Dis ; 35(1): 9-14, 2022 02 01.
Article in English | MEDLINE | ID: covidwho-1528241

ABSTRACT

PURPOSE OF REVIEW: The COVID-19 pandemic materialized in 2020, the year the international community had expected to meet the interim targets to end AIDS by 2030. Forty years into the HIV pandemic, the COVID-19 pandemic challenges the achievements made in HIV and may even reverse some of them. RECENT FINDINGS: This article provides an overview of the impact of COVID-19 on people with, and at risk of, HIV infection. It addresses where the global response to HIV was expected to be by 2020, analyzes the impact of COVID-19 on HIV-related outcomes and reviews the impact of HIV on COVID-19 related outcomes. SUMMARY: The COVID-19 pandemic has had a profound impact on the response to HIV infection through disruption of prevention, testing, and access to antiretroviral treatment, as well as on the management of long-term HIV and mental health. This negative impact has been unequal throughout the world and across populations and deepens inequities in health. HIV does not increase Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) susceptibility once confounders are taken into account and inconsistencies are reported regarding its direct role on clinical severity. In post-COVID-19 scenarios, new models for HIV testing and care are likely to be consolidated. Monitoring responses needs high-quality epidemiological data and collaborative research.


Subject(s)
COVID-19 , HIV Infections , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/epidemiology , Humans , Mental Health , Pandemics/prevention & control , SARS-CoV-2
6.
Ann Intern Med ; 173(7): 536-541, 2020 10 06.
Article in English | MEDLINE | ID: covidwho-614702

ABSTRACT

BACKGROUND: The incidence and severity of coronavirus disease 2019 (COVID-19) among HIV-positive persons receiving antiretroviral therapy (ART) have not been characterized in large populations. OBJECTIVE: To describe the incidence and severity of COVID-19 by nucleos(t)ide reverse transcriptase inhibitor (NRTI) use among HIV-positive persons receiving ART. DESIGN: Cohort study. SETTING: HIV clinics in 60 Spanish hospitals between 1 February and 15 April 2020. PARTICIPANTS: 77 590 HIV-positive persons receiving ART. MEASUREMENTS: Estimated risks (cumulative incidences) per 10 000 persons and 95% CIs for polymerase chain reaction-confirmed COVID-19 diagnosis, hospitalization, intensive care unit (ICU) admission, and death. Risk and 95% CIs for COVID-19 diagnosis and hospital admission by use of the NRTIs tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC), tenofovir alafenamide (TAF)/FTC, abacavir (ABC)/lamivudine (3TC), and others were estimated through Poisson regression models. RESULTS: Of 77 590 HIV-positive persons receiving ART, 236 were diagnosed with COVID-19, 151 were hospitalized, 15 were admitted to the ICU, and 20 died. The risks for COVID-19 diagnosis and hospitalization were greater in men and persons older than 70 years. The risk for COVID-19 hospitalization was 20.3 (95% CI, 15.2 to 26.7) among patients receiving TAF/FTC, 10.5 (CI, 5.6 to 17.9) among those receiving TDF/FTC, 23.4 (CI, 17.2 to 31.1) among those receiving ABC/3TC, and 20.0 (CI, 14.2 to 27.3) for those receiving other regimens. The corresponding risks for COVID-19 diagnosis were 39.1 (CI, 31.8 to 47.6), 16.9 (CI, 10.5 to 25.9), 28.3 (CI, 21.5 to 36.7), and 29.7 (CI, 22.6 to 38.4), respectively. No patient receiving TDF/FTC was admitted to the ICU or died. LIMITATION: Residual confounding by comorbid conditions cannot be completely excluded. CONCLUSION: HIV-positive patients receiving TDF/FTC have a lower risk for COVID-19 and related hospitalization than those receiving other therapies. These findings warrant further investigation in HIV preexposure prophylaxis studies and randomized trials in persons without HIV. PRIMARY FUNDING SOURCE: Instituto de Salud Carlos III and National Institutes of Health.


Subject(s)
Antiretroviral Therapy, Highly Active , Coronavirus Infections/epidemiology , HIV Infections/drug therapy , Pneumonia, Viral/epidemiology , Adenine/analogs & derivatives , Adult , Aged , Betacoronavirus , COVID-19 , Coronavirus Infections/mortality , Dideoxynucleosides , Drug Combinations , Emtricitabine , Female , HIV Infections/mortality , Hospitalization/statistics & numerical data , Humans , Incidence , Intensive Care Units/statistics & numerical data , Lamivudine , Male , Middle Aged , Pandemics , Pneumonia, Viral/mortality , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2 , Severity of Illness Index , Spain/epidemiology , Tenofovir
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