Incidence and Severity of COVID-19 in HIV-Positive Persons Receiving Antiretroviral Therapy : A Cohort Study

Julia Del Amo, Rosa Polo, Santiago Moreno, Asunción Díaz, Esteban Martínez, José Ramón Arribas, Inma Jarrín, Miguel A Hernán, The Spanish HIV/COVID-19 Collaboration, E V Martínez, M J Sierra, M Sastre, R Amillategui, J L Blanco, J R Blanco, J Casado, J Olalla, M Cobos, G Fagúndez, J Gómez-Castellá, R González, C Iniesta, S Martinez, R Tuesta, D Vinuesa, J Hernandez-Quero, A Rivero, M Gallo, A Del Arco, J M García de Lomas, A Dominguez, M J Ríos, L F López-Cortés, N Espinosa, J Macías, J A Pineda, J Santos, J A Terrón, C Hidalgo, G Samperiz, H Navarro, V Asensi, M Rivas, A Campins, M A Ribas, R Pelazas, M R Alemán, J L Pérez-Arellano, J F Lluch, P Geijo, E Martínez-Alfaro, F Mateos, E Ferreira, P Bachiller, J Gómez-Barquero, J Abadía, C Dueñas, L Rodríguez, M A Garcinuño, C Grande, J Sánchez-Navarro, L Buzón, E de Lazzari, A Inciarte, J García-Pérez, A Curran, D Dalmau, M Cairó, M R Coll, D de Mendoza, H Knobel, A Guelar, G Navarro Rubio, M Navarro Vilasaró, A Imaz, D Podzamczer, J Peraire, A Rull, V Diaz-Brito, M Sanmarti, E Negredo, P Domingo, E Molas, A Mariño, N Valcarce, A Ocampo, G Pousada, E Losada, A Antela, A Mena, J A Oteo, J E Losa, M Velasco, J Vergas, V Estrada, F Pulido, M de Lagarde, I Suárez-García, P Ruiz-Seco, A Cabello, M Górgolas, R Montejano, R Micán, J Sanz-Sanz, I de los Santos, M J Pérez-Elías, J Pérez-Molina, P Guisado, J Sanz-Moreno, A Arranz, P Ryan, G Cuevas, A Díaz de Santiago, A A Moreno, M Cervero, J C López Bernaldo de Quiros, F Parras, C Galera, H Albendin, E Bernal, A Muñoz-Pérez, A Soria, M Rivero-Marcotegui, M Ibarguren, J A Iribarren, J Portu, Z Ortiz de Zárate, M Masiá, C Robledano, X Portilla, M Carreres, A Artero, M Madrazo, M Tasias, M Montero, M J Galindo, J Flores, Julia Del Amo, Rosa Polo, Santiago Moreno, Asunción Díaz, Esteban Martínez, José Ramón Arribas, Inma Jarrín, Miguel A Hernán, The Spanish HIV/COVID-19 Collaboration, E V Martínez, M J Sierra, M Sastre, R Amillategui, J L Blanco, J R Blanco, J Casado, J Olalla, M Cobos, G Fagúndez, J Gómez-Castellá, R González, C Iniesta, S Martinez, R Tuesta, D Vinuesa, J Hernandez-Quero, A Rivero, M Gallo, A Del Arco, J M García de Lomas, A Dominguez, M J Ríos, L F López-Cortés, N Espinosa, J Macías, J A Pineda, J Santos, J A Terrón, C Hidalgo, G Samperiz, H Navarro, V Asensi, M Rivas, A Campins, M A Ribas, R Pelazas, M R Alemán, J L Pérez-Arellano, J F Lluch, P Geijo, E Martínez-Alfaro, F Mateos, E Ferreira, P Bachiller, J Gómez-Barquero, J Abadía, C Dueñas, L Rodríguez, M A Garcinuño, C Grande, J Sánchez-Navarro, L Buzón, E de Lazzari, A Inciarte, J García-Pérez, A Curran, D Dalmau, M Cairó, M R Coll, D de Mendoza, H Knobel, A Guelar, G Navarro Rubio, M Navarro Vilasaró, A Imaz, D Podzamczer, J Peraire, A Rull, V Diaz-Brito, M Sanmarti, E Negredo, P Domingo, E Molas, A Mariño, N Valcarce, A Ocampo, G Pousada, E Losada, A Antela, A Mena, J A Oteo, J E Losa, M Velasco, J Vergas, V Estrada, F Pulido, M de Lagarde, I Suárez-García, P Ruiz-Seco, A Cabello, M Górgolas, R Montejano, R Micán, J Sanz-Sanz, I de los Santos, M J Pérez-Elías, J Pérez-Molina, P Guisado, J Sanz-Moreno, A Arranz, P Ryan, G Cuevas, A Díaz de Santiago, A A Moreno, M Cervero, J C López Bernaldo de Quiros, F Parras, C Galera, H Albendin, E Bernal, A Muñoz-Pérez, A Soria, M Rivero-Marcotegui, M Ibarguren, J A Iribarren, J Portu, Z Ortiz de Zárate, M Masiá, C Robledano, X Portilla, M Carreres, A Artero, M Madrazo, M Tasias, M Montero, M J Galindo, J Flores

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.

Conflict of interest statement

Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M20-3689.

Figures

Visual Abstract.. Incidence and Severity of COVID-19…
Visual Abstract.. Incidence and Severity of COVID-19 in HIV-Positive Persons Receiving ART
This study describes the incidence and severity of COVID-19 among 77 590 HIV-positive patients receiving antiretroviral therapy (ART). These findings warrant further investigation of HIV ART in HIV preexposure prophylaxis studies and randomized trials among persons without HIV.
Figure.. Study flow chart of 77 590…
Figure.. Study flow chart of 77 590 HIV-positive persons receiving ART in Spain from 1 February to 15 April 2020.
3TC = lamivudine; ABC = abacavir; ART = antiretroviral therapy; FTC = emtricitabine; ICU = intensive care unit; PCR = polymerase chain reaction; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate.

References

    1. World Health Organization. Coronavirus disease (COVID-19) pandemic. Accessed at on 5 May 2020.
    1. Wu F, Zhao S, Yu B, et al. A new coronavirus associated with human respiratory disease in China. Nature. 2020;579:265-269. [PMID: 32015508] doi:10.1038/s41586-020-2008-3
    1. Government of Spain, Ministry of Health. COVID-19 situation in Spain. Accessed at on 13 May 2020.
    1. European Centre for Disease Prevention and Control. HIV/AIDS surveillance in Europe 2019–2018 data. Accessed at on 10 May 2020.
    1. Blanco JL, Ambrosioni J, Garcia F, et al; COVID-19 in HIV Investigators. COVID-19 in patients with HIV: clinical case series [Letter]. Lancet HIV. 2020;7:e314-e316. [PMID: 32304642] doi:10.1016/S2352-3018(20)30111-9
    1. Haerter G, Spinner D, Roider J, et al. COVID-19 in people living with human immunodeficiency virus: a case series of 33 patients. medRxiv. Preprint posted online 1 May 2020. doi:10.1101/2020.04.28.20073767
    1. Guo W, Ming F, Dong Y et al. A survey for COVID-19 among HIV/AIDS patients in two districts of Wuhan, China. Lancet. Preprint posted 13 March 2020. doi:10.2139/ssrn.3550029
    1. Wang W, Su B, Pang L, et al. High-dimensional immune profiling by mass cytometry revealed immunosuppression and dysfunction of immunity in COVID-19 patients. Cell Mol Immunol. 2020;17:650-652. [PMID: 32346099] doi:10.1038/s41423-020-0447-2
    1. Richardson S, Hirsch JS, Narasimhan M, et al; and the Northwell COVID-19 Research Consortium. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the new york city area. JAMA. 2020. [PMID: 32320003] doi:10.1001/jama.2020.6775
    1. Borobia A, Carcas A, Arnalich F, et al. A cohort of patients with COVID-19 in a major teaching hospital in Europe. J Clin Med. 2020;9:1733. doi:10.3390/jcm9061733
    1. Guan WJ, Ni ZY, Hu Y, et al; China Medical Treatment Expert Group for Covid-19. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382:1708-1720. [PMID: 32109013] doi:10.1056/NEJMoa2002032
    1. Yang J, Zheng Y, Gou X, et al. Prevalence of comorbidities in the novel Wuhan coronavirus (COVID-19) infection: a systematic review and meta-analysis. Int J Infect Dis. Accessed at on 23 March 2020.
    1. Government of Spain, Ministry of Health. Hospital survey of patients with HIV infection. Results 2019. Analysis of the evolution 2004-2019. National Center for Epidemiology–Carlos III Health Institute/National AIDS Plan–GD of Public Health, Quality and Innovation/National Center for Epidemiology. Madrid; May 2020. Accessed at on 25 June 2020.
    1. Alejos B, Suárez-García I, Bisbal O, et al; CoRIS cohort. Choice of the initial antiretroviral treatment for HIV-positive individuals in the era of integrase inhibitors. PLoS One. 2019;14:e0221598. [PMID: 31449566] doi:10.1371/journal.pone.0221598
    1. Sánchez-Conde M, Rodriguez-Centeno J, Dronda F, et al. Frailty phenotype: a clinical marker of age acceleration in the older HIV-infected population. Epigenomics. 2019;11:501-509. [PMID: 30675812] doi:10.2217/epi-2018-0130
    1. Álvarez S, Brañas F, Sánchez-Conde M, et al. Frailty, markers of immune activation and oxidative stress in HIV infected elderly. PLoS One. 2020;15:e0230339. [PMID: 32187205] doi:10.1371/journal.pone.0230339
    1. Chen XP, Cao Y. Consideration of highly active antiretroviral therapy in the prevention and treatment of severe acute respiratory syndrome. Clin Infect Dis. 2004;38:1030-2. [PMID: 15034838]
    1. Chien M, Anderson TK, Jockusch S, et al. Nucleotide analogues as inhibitors of SARS-CoV-2 polymerase. bioRxiv. Preprint posted online 20 March 2020. doi:10.1101/2020.03.18.997585
    1. Elfiky AA. Anti-HCV, nucleotide inhibitors, repurposing against COVID-19. Life Sci. 2020;248:117477. [PMID: 32119961] doi:10.1016/j.lfs.2020.117477
    1. Elfiky AA. Ribavirin, remdesivir, sofosbuvir, galidesivir, and tenofovir against SARS-CoV-2 RNA dependent RNA polymerase (RdRp): a molecular docking study. Life Sci. 2020;253:117592. [PMID: 32222463] doi:10.1016/j.lfs.2020.117592
    1. Ju J, Kumar S, Li X, et al. Nucleotide analogues as inhibitors of viral polymerases. bioRxiv. Preprint posted online 31 January 2020. doi:10.1101/2020.01.30.927574
    1. Peters HL, Ku TC, Seley-Radtke KL. Flexibility as a strategy in nucleoside antiviral drug design. Curr Med Chem. 2015;22:3910-21. [PMID: 26282942]
    1. Sanders JM, Monogue ML, Jodlowski TZ, et al. Pharmacologic treatments for coronavirus disease 2019 (COVID-19): A review. JAMA. 2020. [PMID: 32282022] doi:10.1001/jama.2020.6019
    1. Jockusch S, Tao C, Li X, et al. Triphosphates of the two components in DESCOVY and TRUVADA are inhibitors of the SARS-CoV-2 polymerase. bioRxiv. Preprint posted online 5 April 2020. doi:10.1101/2020.04.03.022939
    1. Government of Spain, National Center of Epidemiology–Institute of Health Carlos III/National AIDS Plan–Subdirectorate General Directorate of Public Health, Quality and Innovation, HIV Surveillance and Behavioral Monitoring Unit. Estimates for HIV continuum of care in Spain, 2016. Madrid; 2019. Accessed at on 14 March 2020.
    1. Government of Spain, Ministry of Health, Alerts and Emergencies Coordination Center. Scientific and technical information on COVID-19. Accessed at on 18 April 2020.
    1. European Medicines Agency, Committee for Medicinal Products for Human Use. Assessment report: Vemlidy. Accessed at on 16 March 2020.
    1. Zídek Z, Franková D, Holý A. Activation by 9-(R)-[2-(phosphonomethoxy)propyl]adenine of chemokine (RANTES, macrophage inflammatory protein 1alpha) and cytokine (tumor necrosis factor alpha, interleukin-10 [IL-10], IL-1beta) production. Antimicrob Agents Chemother. 2001;45:3381-6. [PMID: 11709312]
    1. Zídek Z, Potmesil P, Kmoníèková E, et al. Immunobiological activity of N-[2-(phosphonomethoxy)alkyl] derivatives of N6-substituted adenines, and 2,6-diaminopurines. Eur J Pharmacol. 2003;475:149-59. [PMID: 12954371]
    1. Kostecká P, Holý A, Farghali H, et al. Differential effects of acyclic nucleoside phosphonates on nitric oxide and cytokines in rat hepatocytes and macrophages. Int Immunopharmacol. 2012;12:342-9. [PMID: 22198073] doi:10.1016/j.intimp.2011.12.005
    1. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497-506. [PMID: 31986264] doi:10.1016/S0140-6736(20)30183-5
    1. Melchjorsen J, Risør MW, Søgaard OS, et al. Tenofovir selectively regulates production of inflammatory cytokines and shifts the IL-12/IL-10 balance in human primary cells. J Acquir Immune Defic Syndr. 2011;57:265-75. [PMID: 21471820] doi:10.1097/QAI.0b013e3182185276
    1. Patterson KB, Prince HA, Kraft E, et al. Penetration of tenofovir and emtricitabine in mucosal tissues: implications for prevention of HIV-1 transmission. Sci Transl Med. 2011;3:112re4. [PMID: 22158861] doi:10.1126/scitranslmed.3003174
    1. Cottrell ML, Garrett KL, Prince HMA, et al. Single-dose pharmacokinetics of tenofovir alafenamide and its active metabolite in the mucosal tissues. J Antimicrob Chemother. 2017;72:1731-1740. [PMID: 28369415] doi:10.1093/jac/dkx064
    1. Di Mascio M, Srinivasula S, Bhattacharjee A, et al. Antiretroviral tissue kinetics: in vivo imaging using positron emission tomography. Antimicrob Agents Chemother. 2009;53:4086-95. [PMID: 19667288] doi:10.1128/AAC.00419-09
    1. Twigg HL, Schnizlein-Bick CT, Weiden M, et al. Measurement of antiretroviral drugs in the lungs of HIV-infected patients. HIV Ther. 2010;4:247-251. [PMID: 20436781]
    1. Park SJ, Yu KM, Kim YI, et al. Antiviral efficacies of FDA-approved drugs against SARS-CoV-2 infection in ferrets. mBio. 2020;11. [PMID: 32444382] doi:10.1128/mBio.01114-20
    1. Alejos B, Hernando V, Iribarren J, et al; CoRIS (Cohort of the Spanish Network on HIVAIDS Research). Overall and cause-specific excess mortality in HIV-positive persons compared with the general population: Role of HCV coinfection. Medicine (Baltimore). 2016;95:e4727. [PMID: 27603368] doi:10.1097/MD.0000000000004727
    1. Desai S, Landay A. Early immune senescence in HIV disease. Curr HIV/AIDS Rep. 2010;7:4-10. [PMID: 20425052] doi:10.1007/s11904-009-0038-4
    1. Horvath S, Levine AJ. HIV-1 infection accelerates age according to the epigenetic clock. J Infect Dis. 2015;212:1563-73. [PMID: 25969563] doi:10.1093/infdis/jiv277
    1. Gross AM, Jaeger PA, Kreisberg JF, et al. Methylome-wide analysis of chronic HIV infection reveals five-year increase in biological age and epigenetic targeting of HLA. Mol Cell. 2016;62:157-168. [PMID: 27105112] doi:10.1016/j.molcel.2016.03.019
    1. Deeks SG. HIV infection, inflammation, immunosenescence, and aging. Annu Rev Med. 2011;62:141-55. [PMID: 21090961] doi:10.1146/annurev-med-042909-093756
    1. Lipsitch M, Donnelly CA, Fraser C, et al. Potential biases in estimating absolute and relative case-fatality risks during outbreaks. PLoS Negl Trop Dis. 2015;9:e0003846. [PMID: 26181387] doi:10.1371/journal.pntd.0003846
    1. National Institutes of Health, U.S. National Library of Medicine. Randomized Clinical Trial for the Prevention of SARS-CoV-2 Infection (COVID-19) in Healthcare Personnel (EPICOS). Accessed at 19%29+in+healthcare+personnel&draw = 2&rank = 1 on 2 April 2020.

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa