Tenofovir-Containing Antiretroviral Therapy and Clinical Outcomes of SARS-CoV-2 Infection in People Living with HIV
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. Participants
2.3. Data Collection
2.4. Statistical Analyses
3. Results
3.1. Tenofovir vs. Non-Tenofovir Group Comparison
3.2. Model 1: Variables Associated with the Requirement of Oxygen Supplementation
3.3. Model 2: Evaluation of Comorbidities Associated with the Requirement of Oxygen Supplementation
3.4. TDF vs. Non-TDF Group Comparison
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Appendix A
TDF (n = 733) | Non-TDF (TAF and Others) (n = 422) | p | |
---|---|---|---|
n (%) * | n (%) * | ||
Male sex | 479 (65.3) | 278 (66) | 0.8 |
Age, years (median; IQR) | 44 (36–51) | 48 (38–56) | <0.001 |
Comorbidities | 269 (36.8) | 173 (41.2) | 0.13 |
Virologic suppression (<20 copies/mL) | 583 (79.9) | 349 (82.7) | 0.24 |
CD4 T-cell count, cells/μL (median; IQR) | 592.5 (430–800) | 632 (470–808) | 0.06 |
COVID-19 vaccination (at least one dose) | 145 (25.6) | 102 (32.6) | 0.028 |
Tomographic abnormalities | 97 (13.8) | 42 (10.5) | 0.11 |
Hospitalization | 115 (16.5) | 70 (17.2) | 0.75 |
Oxygen therapy | 67 (9.2) | 47 (11.2) | 0.25 |
COVID-19 therapy | 81 (11.1) | 51 (12.2) | 0.56 |
Mortality | 7 (1) | 6 (1.4) | 0.46 |
References
- Our World in Data. Available online: https://ourworldindata.org/explorers/coronavirus-data-explorer?facet=none&Metric=Confirmed+cases&Interval=7-day+rolling+average&Relative+to+Population=true&Color+by+test+positivity=false&country=ARG%29.~ARG.&Metric=Confirmed+cases (accessed on 10 February 2023).
- World Health Organization. Therapeutics and COVID-19: Living Guideline. 2023. Available online: https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2022.4 (accessed on 18 February 2023).
- Cao, B.; Wang, Y.; Wen, D.; Lui, W.; Wang, J.; Fan, G.; Ruan, L.; Song, B.; Cai, Y.; Wei, M.; et al. A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe COVID-19. N. Engl. J. Med. 2020, 382, 1787–1799. [Google Scholar] [CrossRef]
- Zanella, I.; Zizioli, D.; Castelli, F.; Quirós-Roldan, E. Tenofovir, Another Inexpensive, Well-Known and Widely Available Old Drug Repurposed for SARS-COV-2 Infection. Pharmaceuticals 2021, 14, 454. [Google Scholar] [CrossRef]
- Toor, H.G.; Banerjee, D.I.; Rath, S.L.; Darji, S.A. Computational drug re-purposing targeting the spike glycoprotein of SARS-CoV-2 as an effective strategy to neutralize COVID-19. Eur. J. Pharmacol. 2021, 890, 173720. [Google Scholar] [CrossRef]
- Yun, Y.; Song, H.; Ji, Y.; Huo, D.; Han, F.; Li, F.; Jiang, N. Identification of therapeutic drugs against COVID-19 through computational investigation on drug repurposing and structural modification. J. Biomed. Res. 2020, 34, 458–469. [Google Scholar] [CrossRef]
- Clososki, G.C.; Soldi, R.A.; da Silva, R.M.; Guaratini, T.; Lopes, J.N.; Pereira, P.R.; Lopes, J.L.; dos Santos, T.; Martins, R.B.; Costa, C.S.; et al. Tenofovir Disoproxil Fumarate: New Chemical Developments and Encouraging in vitro Biological Results for SARS-CoV-2. J. Braz. Chem. Soc. 2020, 31, 1552–1556. [Google Scholar] [CrossRef]
- Li, G.; Park, L.S.; Lodi, S.; Logan, R.W.; Cartwright, E.J.; Aoun-Barakat, L.; Casas, J.P.; Dickerman, B.A.; Rentsch, C.T.; Justice, A.C.; et al. Tenofovir disoproxil fumarate and coronavirus disease 2019 outcomes in men with HIV. AIDS 2022, 36, 1689–1696. [Google Scholar] [CrossRef]
- Del Amo, J.; Polo, R.; Moreno, S.; Díaz, A.; Martínez, E.; Arribas, J.R.; Jarrín, I.; Hernán, M.A. Incidence and Severity of COVID-19 in HIV-Positive Persons Receiving Antiretroviral Therapy. A Cohort Study. Ann. Intern. Med. 2020, 173, 536–541. [Google Scholar] [CrossRef]
- Boulle, A.; Davies, M.-A.; Hussey, H.; Ismail, M.; Morden, E.; Vundle, Z.; Zweigenthal, V.; Mahomed, H.; Paleker, M.; Pienaar, D.; et al. Risk Factors for Coronavirus Disease 2019 (COVID-19) Death in a Population Cohort Study from the Western Cape Province, South Africa. Clin. Infect. Dis. 2021, 73, e2005–e2015. [Google Scholar] [CrossRef]
- Mateos-Muñoz, B.; Buti, M.; Fernández Vázquez, I.; Hernández Conde, M.; Bernal-Monterde, V.; Diaz-Fontenla, F.; Morillas, R.M.; García-Buey, L.; Badía, E.; Miquel, M.; et al. Tenofovir Disoproxil Fumarate Reduces the Severity of COVID-19 in Patients with Chronic Hepatitis B. Dig. Dis. Sci. 2023, 3, 1–7. [Google Scholar] [CrossRef] [PubMed]
- Geretti, A.M.; Stockdale, A.J.; Kelly, S.H.; Cevik, M.; Collins, S.; Waters, L.; Villa, G.; Docherty, A.; Harrison, E.M.; Turtle, L.; et al. Outcomes of Coronavirus Disease 2019 (COVID-19) Related Hospitalization Among People With Human Immunodeficiency Virus (HIV) in the ISARIC World Health Organization (WHO) Clinical Characterization Protocol (UK): A Prospective Observational Study. Clin. Infect. Dis. 2021, 73, e2095–e2106. [Google Scholar] [CrossRef]
- Bertagnolio, S.; Thwin, S.S.; Silva, R.; Nagarajan, S.; Jassat, W.; Fowler, R.; Haniffa, R.; Reveiz, L.; Ford, N.; Doherty, M.; et al. Clinical features of, and risk factors for, severe or fatal COVID-19 among people living with HIV admitted to hospital: Analysis of data from the WHO Global Clinical Platform of COVID-19. Lancet HIV 2022, 9, E486–E495. [Google Scholar] [CrossRef]
- Bhaskaran, K.; Rentsch, C.T.; MacKenna, B.; Schultze, A.; Mehrkar, A.; Bates, C.J.; Eggo, R.M.; Morton, C.E.; Bacon, S.C.; Inglesby, P.; et al. HIV infection and COVID-19 death: A population-based cohort analysis of UK primary care data and linked national death registrations within the OpenSAFELY platform. Lancet HIV 2021, 8, e24–e32. [Google Scholar] [CrossRef]
- Jilich, D.; Skrzat-Klapaczyńska, A.; Fleischhans, L.; Bursa, D.; Antoniak, S.; Balayan, T.; Begovac, J.; Cicic, A.; Dragovic, G.; Goekengin, D.; et al. National strategies for vaccination against COVID-19 in people living with HIV in Central and Eastern European region. HIV Med. 2022, 23, 546–552. [Google Scholar] [CrossRef] [PubMed]
- Varshney, K.; Ghosh, P.; Stiles, H.; Iriowen, R. Risk Factors for COVID-19 Mortality Among People Living with HIV: A Scoping Review. AIDS Behav. 2022, 26, 2256–2265. [Google Scholar] [CrossRef] [PubMed]
- Bhiva, D.; Eacs, G.; Polish Scientific AIDS Society and Portuguese Association for the Clinical Study of AIDS (APECS). Statement on Risk of COVID-19 for People Living with HIV (PLWH) and SARS-CoV-2 Vaccine Advice for Adults Living with HIV. 2021. Available online: https://www.bhiva.org/joint-statement-on-risk-of-COVID-19-for-PLWH-and-SARS-CoV-2-vaccine-advice (accessed on 20 February 2023).
- Dirección de Respuesta al VIH, ITS, Hepatitis Virales y Tuberculosis. Ministerio de Salud, Argentina. Boletín Número 39 de Respuesta al VIH y las ITS en la Argentina. 2022. Available online: https://bancos.salud.gob.ar/recurso/boletin-ndeg-39-respuesta-al-vih-y-las-its-en-la-argentina (accessed on 15 February 2023).
- Ministerio de Salud, Argentina. Consenso Sobre el Uso de Pruebas Diagnósticas para SARS-CoV-2, Versión 2. 2021. Available online: https://bancos.salud.gob.ar/recurso/consenso-sobre-el-uso-de-pruebas-diagnosticas-para-sars-cov-2. (accessed on 15 February 2023).
- Tesoriero, J.M.; Swain, C.-A.; Pierce, J.L.; Zamboni, L.; Wu, M.; Holtgrave, D.R.; Gonzalez, C.J.; Udo, T.; Morne, J.E.; Hart-Malloy, R.; et al. COVID-19 Outcomes among Persons Living With or Without Diagnosed HIV Infection in New York State. JAMA Netw. Open 2021, 4, e2037069. [Google Scholar] [CrossRef]
- Dandachi, D.; Geiger, G.; Montgomery, M.W.; Karmen-Tuohy, S.; Golzy, M.; Antar, A.A.; Llibre, J.M.; Camazine, M.; Díaz-De Santiago, A.; Carlucci, P.M.; et al. Characteristics, Comorbidities, and Outcomes in a Multicenter Registry of Patients with Human Immunodeficiency Virus and Coronavirus Disease 2019. Clin. Infect. Dis. 2021, 73, e1964–e1972. [Google Scholar] [CrossRef] [PubMed]
- Brown, A.E.; Croxford, S.E.; Nash, S.; Khawam, J.; Kirwan, P.; Kall, M.; Bradshaw, D.; Sabin, C.; Miller, R.F.; Post, F.A.; et al. COVID-19 mortality among people with diagnosed HIV compared to those without during the first wave of the COVID-19 pandemic in England. HIV Med. 2022, 23, 90–102. [Google Scholar] [CrossRef]
- Inciarte, A.; Gonzalez-Cordon, A.; Rojas, J.; Torres, B.; de Lazzari, E.; de la Mora, L.; Martinez-Rebollar, M.; Laguno, M.; Callau, P.; Gonzalez-Navarro, A.; et al. Clinical characteristics, risk factors, and incidence of symptomatic coronavirus disease 2019 in a large cohort of adults living with HIV: A single-center, prospective observational study. AIDS 2020, 34, 1775–1780. [Google Scholar] [CrossRef]
- Stoeckle, K.; Johnston, C.D.; Jannat-Khah, D.P.; Williams, S.C.; Ellman, T.M.; Vogler, M.A.; Gulick, R.M.; Glesby, M.J.; Choi, J.J. COVID-19 in Hospitalized Adults with HIV. Open Forum Infect. Dis. 2020, 7, ofaa327. [Google Scholar] [CrossRef]
- Vizcarra, P.; Pérez-Elías, M.J.; Quereda, C.; Moreno, A.; Vivancos, M.J.; Dronda, F.; Casado, J.L. Description of COVID-19 in HIV-infected individuals: A single-centre, prospective cohort. Lancet HIV 2020, 7, E554–E564. [Google Scholar] [CrossRef]
- Lee, M.J.; Snell, L.B.; Douthwaite, S.T.; Fidler, S.; Fitzgerald, N.; Goodwin, L.; Hamzah, L.; Kulasegaram, R.; Lawrence, S.; Lwanga, J.; et al. Clinical outcomes of patients with and without HIV hospitalized with COVID-19 in England during the early stages of the pandemic: A matched retrospective multi-centre analysis (RECEDE-C19 study). HIV Med. 2022, 23, 121–133. [Google Scholar] [CrossRef]
- Riva, A.; Conti, F.; Bernacchia, D.; Pezzati, L.; Sollima, S.; Merli, S.; Siano, M.; Lupo, A.; Rusconi, S.; Cattaneo, D.; et al. Darunavir does not prevent SARS-CoV-2 infection in HIV patients. Pharmacol. Res. 2020, 157, 104826. [Google Scholar] [CrossRef] [PubMed]
- Horby, P.W.; Mafham, M.; Bell, J.L.; Linsell, L.; Staplin, N.; Emberson, J.; Palfreeman, A.; Raw, J.; Elmahi, E.; Prudon, B.; et al. RECOVERY Collaborative Group. Lopinavir-ritonavir in patients admitted to hospital with COVID-19 (RECOVERY): A randomised, controlled, open-label, platform trial. Lancet 2020, 396, 1345–1352. [Google Scholar] [CrossRef]
- Jockusch, S.; Tao, C.; Li, X.; Anderson, T.K.; Chien, M.; Kumar, S.; Russo, J.J.; Kirchdoerfer, R.N.; Ju, J. Triphosphates of the Two Components in DESCOVY and TRUVADA are Inhibitors of the SARS-CoV-2 Polymerase. bioRxiv 2020. [Google Scholar] [CrossRef]
- Del Amo, J.; Polo, R.; Moreno, S.; Diaz, A.; Martínez, E.; Arribas, J.R.; Jarrín, I.; Hernán, M.A. Antiretrovirals and Risk of COVID-19 Diagnosis and Hospitalization in HIV-Positive Persons. Epidemiology 2020, 31, e49–e51. [Google Scholar] [CrossRef] [PubMed]
- Nomah, D.K.; Reyes-Urueña, J.; Díaz, Y.; Moreno, S.; Aceiton, J.; Bruguera, A.; Vivanco-Hidalgo, R.M.; Casabona, J.; Domingo, P.; Navarro, J.; et al. Impact of tenofovir on SARS-CoV-2 infection and severe outcomes among people living with HIV: A propensity score-matched study. J. Antimicrob. Chemother. 2022, 77, 2265–2273. [Google Scholar] [CrossRef]
- Ayerdi, O.; Puerta, T.; Clavo, P.; Vera, M.; Ballesteros, J.; Fuentes, M.E.; Estrada, V.; Rodríguez, C.; Del Romero, J.; Sandoval Study Group. Preventive Efficacy of Tenofovir/Emtricitabine Against Severe Acute Respiratory Syndrome Coronavirus 2 among Pre-Exposure Prophylaxis Users. Open Forum Infect. Dis. 2020, 7, ofaa455. [Google Scholar] [CrossRef]
- Cooper, T.J.; Woodward, B.L.; Alom, S.; Harky, A. Coronavirus disease 2019 (COVID-19) outcomes in HIV/AIDS patients: A systematic review. HIV Med. 2020, 21, 567–577. [Google Scholar] [CrossRef]
- Gervasoni, C.; Meraviglia, P.; Riva, A.; Giacomelli, A.; Oreni, L.; Minisci, D.; Atzori, C.; Ridolfo, A.; Cattaneo, D. Clinical Features and Outcomes of Patients with Human Immunodeficiency Virus with COVID-19. Clin. Infect. Dis. 2020, 71, 2276–2278. [Google Scholar] [CrossRef]
- Wassner, C.; Bradley, N.; Lee, Y. A Review and Clinical Understanding of Tenofovir: Tenofovir Disoproxil Fumarate versus Tenofovir Alafenamide. J. Int. Assoc. Provid. AIDS Care 2020, 19, 2325958220919231. [Google Scholar] [CrossRef]
- Ministerio de Salud de la Nación. Plan Estratégico para la Vacunación contra la COVID-19 en la República Argentina. 2020. Available online: https://www.argentina.gob.ar/sites/default/files/coronavirus-vacuna-plan-estrategico-vacunacion-covid-19-diciembre-2020.pdf (accessed on 17 April 2023).
- Platto, S.; Wang, Y.; Zhou, J.; Carafoli, E. History of the COVID-19 pandemic: Origin, explosion, worldwide spreading. Biochem. Biophys. Res. Commun. 2021, 538, 14–23. [Google Scholar] [CrossRef] [PubMed]
- Tatar, M.; Shoorekchali, J.M.; Faraji, M.R.; Seyyedkolaee, M.A.; Pagán, J.A.; Wilson, F.A. COVID-19 vaccine inequality: A global perspective. J. Glob. Health 2022, 12, 03072. [Google Scholar] [CrossRef] [PubMed]
TDF/TAF (n = 927) | Non-TDF/TAF (n = 228) | p | |
---|---|---|---|
n (%) | n (%) | ||
Male sex | 612 (66) | 145 (63.8) | 0.54 |
Age, years (median; IQR) | 44 (36–51) | 50 (39–58) | <0.001 |
Comorbidities | 349 (37.8) | 93 (41.1) | 0.35 |
Hypertension | 107 (11.5) | 36 (15.8) | 0.08 |
Diabetes | 54 (5.8) | 20 (8.8) | 0.10 |
Heart failure | 3 (0.3) | 5 (2.2) | 0.002 |
Obesity | 29 (12.7) | 152 (16.4) | 0.17 |
Asthma | 17 (1.8) | 3 (1.3) | 0.59 |
Smoking habit | 72 (7.8) | 18 (7.9) | 0.95 |
Chronic steroid use | 1 (0.1) | 4 (1.8) | 0.001 |
Chronic kidney disease | 5 (0.5) | 16 (7) | <0.001 |
Virologic suppression (<20 copies/mL) | 749 (81.1) | 183 (80.3) | 0.78 |
CD4 T-cell count, cells/μL (median; IQR) | 597 (434–800) | 656.5 (472.5–824) | 0.04 |
Low CD4 count (<350 cells/μL) | 147 (16) | 22 (9.7) | 0.02 |
COVID-19 vaccination (at least one dose) | 193 (26.5) | 54 (35.8) | 0.02 |
Symptomatic COVID-19 | 888 (95.8) | 221 (96.9) | 0.42 |
Tomographic abnormalities (n = 139/1104) * | 112 (12.7) | 27 (12.3) | 0.88 |
Hospitalization (n = 185/1106) * | 144 (16.2) | 41 (18.7) | 0.37 |
Oxygen therapy (n = 114/1149) * | 83 (9) | 31 (13.8) | 0.03 |
COVID-19 therapy (n = 132/1150) * | 102 (11) | 30 (13.3) | 0.33 |
Mortality (n = 13/1148) * | 8 (0.9) | 5 (2.2) | 0.09 |
Variable | OR (95% CI) | p |
---|---|---|
Non-tenofovir ART | 1.63 (1.05–2.53) | 0.03 |
Age (years) | 1.05 (1.03–1.07) | <0.001 |
CD4 T-cell count (<350 cells/μL) | 2.58 (1.65–4.04) | <0.001 |
Comorbidities | 2.53 (1.67–3.85) | <0.001 |
History of COVID vaccination (at least one dose) | 0.24 (0.1–0.55) | 0.001 |
Variable | OR | 95% CI | p |
---|---|---|---|
Non-tenofovir ART | 2.2 | 1.17–4.11 | 0.014 |
History of COVID-19 vaccination (at least one dose) | 0.19 | 0.08–0.47 | <0.001 |
CD4 T-cell count (<350 cells/μL) | 3.97 | 2.20–7.16 | <0.001 |
Age | 1.04 | 1.01–1.06 | 0.008 |
Comorbidities | 2.07 | 1.20–3.58 | 0.009 |
Variable | OR (95% CI) | p |
---|---|---|
Chronic kidney disease | 10.95 (4.54–26.39) | <0.001 |
Chronic steroid use | 2.28 (0.25–20.58) | 0.46 |
Heart failure | 5.57 (1.31–23.61) | 0.02 |
Other comorbidities | 1.75 (1.19–2.59) | 0.01 |
Variable | OR | 95% CI | p |
---|---|---|---|
Non-tenofovir ART | 1.81 | 0.93–3.54 | 0.08 |
History of COVID-19 vaccination (at least one dose) | 0.17 | 0.07–0.43 | <0.001 |
CD4 T-cell count (<350 cells/μL) | 4.22 | 2.34–7.62 | <0.001 |
Age | 1.03 | 1.00–1.06 | 0.02 |
Chronic kidney disease | 23.61 | 4.54–122.68 | <0.001 |
Heart failure | 0.34 | 0.02–5.04 | 0.44 |
Other comorbidities | 1.81 | 1.03–3.16 | 0.04 |
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Rombini, M.F.; Cecchini, D.; Diana Menendez, S.; Calanni, L.; Cuini, R.; Obieta, E.; Greco, M.M.; Morales, F.; Morganti, L.; Migazzi, C.; et al. Tenofovir-Containing Antiretroviral Therapy and Clinical Outcomes of SARS-CoV-2 Infection in People Living with HIV. Viruses 2023, 15, 1127. https://doi.org/10.3390/v15051127
Rombini MF, Cecchini D, Diana Menendez S, Calanni L, Cuini R, Obieta E, Greco MM, Morales F, Morganti L, Migazzi C, et al. Tenofovir-Containing Antiretroviral Therapy and Clinical Outcomes of SARS-CoV-2 Infection in People Living with HIV. Viruses. 2023; 15(5):1127. https://doi.org/10.3390/v15051127
Chicago/Turabian StyleRombini, María F., Diego Cecchini, Sofía Diana Menendez, Liliana Calanni, Rosana Cuini, Elena Obieta, María M. Greco, Fabricio Morales, Laura Morganti, Claudia Migazzi, and et al. 2023. "Tenofovir-Containing Antiretroviral Therapy and Clinical Outcomes of SARS-CoV-2 Infection in People Living with HIV" Viruses 15, no. 5: 1127. https://doi.org/10.3390/v15051127