Impact of tenofovir on SARS-CoV-2 infection and severe outcomes among people living with HIV: a propensity score-matched study

Nomah, Daniel K.; Reyes-Urueña, Juliana; Díaz, Yesika; Moreno-Fornés, Sergio; Aceitón, Jordi; Bruguera, Andreu; Vivanco-Hidalgo, Rosa María; Casabona, Jordi; Domingo, Peré; Navarro, Jordi; Imaz, Arkaitz; Deig, Elisabet; Navarro, Gemma; Llibre, JM; Miró, José M.; Muntada, Esteve; Esteve, Anna; Fanjul, Francisco; Falcó, Vicenç; Knobel, Hernando; Mallolas, Josép; Tiraboschi, Juan; Curran, Adrían; Burgos, Joaquín; Revollo, Boris; Gracia, María Pilar Rivero; Gutierrez, María del Mar; Murillas, Javier; Homar, Francisco Bujosa; Fernández-Montero, José Vicente; González, Eva López; Peraire, Joaquim; Force, Lluís; León, Elena; Hortos, Miquel; Vilaró, Ingrid; Ortí, Amat; Dalmau, David; Jaén, Àngels; Lazzari, Elisa de; Berrocal, Leire; Rodríguez, Lucía; Gargoulas, Freya; Vanrell, Toni; Carlos, José; Vilà, Josep; Martínez, M. Díez; Morell, Bibiana; Tamayo, Maribel; Palacio, Jorge; Ambrosioni, Juan; Laguno, Montse; Martı́nez-Rebollar, Marı́a; Blanco, José Luis Santiago; García, Felipe Andreo; Torres, Berta; Mora, Lorena de la; Inciarte, Alexy; Ugarte, Ainoa; Chivite, Iván; González-Cordón, Ana; Leal, Lorna; Jou, Antoni; Negredo, Eugènia; Saumoy, María; Silva, Ana; Scévola, Sofía; Suanzes, Paula; Alvarez, Patricia; Mur, Isabel; Jaume, Melchor Riera; García-Gasalla, Mercedes; Ribas, Maria Àngels; Campins, Antoni A; Peñaranda, María; Martín, María Luisa; Haydee, Helem; Calzado, Sònia; Cervantes, Manel; Navarro, M. Ortin; Payeras, Antoni; Cifuentes, Carmen; Villoslada, Aroa; Sorní, Patrícia; Molero, Marta; Abdulghani, Nadia; Comella, Thaïs; Sola, Rocio; Vargas, Montserrat; Viladés, Consuleo; Martí, Anna; Yeregui, Elena; Rull, Anna; Barrufet, Pilar; Arbones, Laia; Chamarro, Elena; Escrig, Cristina; Cairó, Mireia; Martínez-Lacasa, Xavier; Font, Roser; Macorigh, Lizza; Hernández, Juanse

doi:10.1093/jac/dkac177

Cited by 14 publications

(14 citation statements)

References 23 publications

(32 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our estimates are consistent with those from observational studies conducted in Spain [6,14,15], South Africa [7], and the United States [9]. These studies, which preferentially included COVID-19 cases that were severe enough to be diagnosed, found a lower risk of severe COVID-19 among HIV-positive individuals on TDF/ FTC compared with other NRTI combinations.…”

Section: Discussionsupporting

confidence: 88%

Tenofovir disoproxil fumarate/emtricitabine and severity of coronavirus disease 2019 in people with HIV infection

Amo

Polo

Moreno

et al. 2022

Aids

View full text Add to dashboard Cite

Background: Effective, safe, and affordable antivirals are needed for coronavirus disease 2019 (COVID-19). Several lines of research suggest that tenofovir may be effective against COVID-19, but no large-scale human studies with appropriate adjustment for comorbidities have been conducted. Methods: We studied HIV-positive individuals on antiretroviral therapy (ART) in 2020 at 69 HIV clinics in Spain. We collected data on sociodemographics, ART, CD4+ cell count, HIV-RNA viral-load, comorbidities and the following outcomes: laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, COVID-19 hospitalization, intensive care unit (ICU) admission and death. We compared the 48-week risks for individuals receiving tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC), tenofovir alafenamide (TAF)/FTC, abacavir (ABC)/lamivudine (3TC), and other regimes. All estimates were adjusted for clinical and sociodemographic characteristics via inverse probability weighting. Results: Of 51 558 eligible individuals, 39.6% were on TAF/FTC, 11.9% on TDF/FTC, 26.6% on ABC/3TC, 21.8% on other regimes. There were 2402 documented SARS-CoV-2 infections (425 hospitalizations, 45 ICU admissions, 37 deaths). Compared with TAF/FTC, the estimated risk ratios (RR) (95% confidence interval) of hospitalization were 0.66 (0.43, 0.91) for TDF/FTC and 1.29 (1.02, 1.58) for ABC/3TC, the RRs of ICU admission were 0.28 (0.11, 0.90) for TDF/FTC and 1.39 (0.70, 2.80) for ABC/3TC, and the RRs of death were 0.37 (0.23, 1.90) for TDF/FTC and 2.02 (0.88–6.12) for ABC/3TC. The corresponding RRs of hospitalization for TDF/FTC were 0.49 (0.24, 0.81) in individuals ≥50 years and 1.15 (0.59, 1.93) in younger individuals. Discussion: Compared with other antiretrovirals, TDF/FTC lowers COVID-19 severity among HIV-positive individuals with virological control. This protective effect may be restricted to individuals aged 50 years and older.

show abstract

Section: Discussionsupporting

confidence: 88%

Tenofovir disoproxil fumarate/emtricitabine and severity of coronavirus disease 2019 in people with HIV infection

Amo

Polo

Moreno

et al. 2022

Aids

View full text Add to dashboard Cite

show abstract

“…This potential protective effect is biologically plausible due to the ability of nucleotide analog reverse transcriptase inhibitors (NRTIs) to inhibit the SARS-CoV-2 RNA-dependent RNA polymerase [ 30 , 31 ]. However, others did not find such an association [ 7 , 32 ]. These contradictory findings may be the consequence of the baseline characteristics of TDF/FTC-users, which are intrinsically associated with a more favorable outcome of SARS-CoV-2 infection.…”

Section: Incidence and Clinical Outcome Of Sars-cov-2 Infection In Plwhmentioning

confidence: 99%

Immunologic Interplay Between HIV/AIDS and COVID-19: Adding Fuel to the Flames?

et al. 2023

View full text Add to dashboard Cite

Purpose of Review HIV/AIDS and COVID-19 have been the major pandemics overwhelming our times. Given the enduring immune disfunction featuring people living with HIV (PLWH) despite combination antiretroviral therapy (cART), concerns for higher incidence and severity of SARS-CoV-2 infection as well as for suboptimal responses to the newly developed vaccines in this population arose early during the pandemics. Herein, we discuss the complex interplay between HIV and SARS-CoV-2, with a special focus on the immune responses to SARS-CoV-2 natural infection and vaccination in PLWH. Recent Findings Overall, current literature shows that COVID-19 severity and outcomes may be worse and immune responses to infection or vaccination lower in PLWH with poor CD4 + T-cell counts and/or uncontrolled HIV viremia. Data regarding the risk of post-acute sequelae of SARS-CoV-2 infection (PASC) among PLWH are extremely scarce, yet they seem to suggest a higher incidence of such condition. Summary Scarce immunovirological control appears to be the major driver of weak immune responses to SARS-CoV-2 infection/vaccination and worse COVID-19 outcomes in PLWH. Therefore, such individuals should be prioritized for vaccination and should receive additional vaccine doses. Furthermore, given the potentially higher risk of developing long-term sequelae, PLWH who experienced COVID-19 should be ensured a more careful and prolonged follow-up.

show abstract

“…The nucleoside analogue, tenofovir disoproxil fumarate is an HIV drug (Desai et al, 2017). It has entered into COVID-19 clinical trials but so far has yet to prove its efficacy both clinically (Parienti et al, 2021;Nomah et al, 2022), in small animal models (Park et al, 2020), ex vivo and in vitro (Choy et al, 2020;Feng et al, 2022). Our identification of tenofovir disoproxil fumarate as a cell type-specific potent fusion inhibitor may open a new avenue for development of tenofovir disoproxil fumarate in synergistic therapeutics.…”

Section: Discussionmentioning

confidence: 99%

Fusion assays for screening of fusion inhibitors targeting SARS-CoV-2 entry and syncytia formation

Chan

2022

Front. Pharmacol.

View full text Add to dashboard Cite

Virus fusion process is evolutionarily conserved and provides a promising pan-viral target. Cell-cell fusion leads to syncytial formation and has implications in pathogenesis, virus spread and immune evasion. Drugs that target these processes can be developed into anti-virals. Here, we have developed sensitive, rapid, adaptable fusion reporter gene assays as models for plasma membrane and alternative fusion pathways as well as syncytial fusion in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and have confirmed their specificity using neutralizing antibodies and specific protease inhibitors. The fusion report gene assays are more sensitive and unbiased than morphological fusion assay. The fusion assays can differentiate between transmembrane serine protease 2 (TMPRSS2)-dependency in TMPRSS2(+) cells and trypsin-dependency in angiotensin-converting enzyme 2 (ACE2)(+)TMPRSS2(-) cells. Moreover, we have identified putative novel fusion processes that are triggered by an acidic pH with and without trypsin. Coupled with morphological fusion criteria, we have found that syncytia formation is enhanced by TMPRSS2 or trypsin. By testing against our top drug hits previously shown to inhibit SARS-CoV-2 pseudovirus infection, we have identified several fusion inhibitors including structurally related lopsided kite-shaped molecules. Our results have important implications in the development of universal blockers and synergistic therapeutics and the small molecule inhibitors can provide important tools in elucidating the fusion process.

show abstract

Impact of tenofovir on SARS-CoV-2 infection and severe outcomes among people living with HIV: a propensity score-matched study

Cited by 14 publications

References 23 publications

Tenofovir disoproxil fumarate/emtricitabine and severity of coronavirus disease 2019 in people with HIV infection

Tenofovir disoproxil fumarate/emtricitabine and severity of coronavirus disease 2019 in people with HIV infection

Immunologic Interplay Between HIV/AIDS and COVID-19: Adding Fuel to the Flames?

Fusion assays for screening of fusion inhibitors targeting SARS-CoV-2 entry and syncytia formation

Contact Info

Product

Resources

About