Semin Respir Crit Care Med 2023; 44(01): 035-049
DOI: 10.1055/s-0042-1758852
Review Article

HIV and COVID-19 Disease

Jacqui P. Venturas
1   Department of Internal Medicine and Pulmonology, Charlotte Maxeke Johannesburg Academic Hospital and Universtity of the Witwatersrand, Johannesburg, South Africa
› Author Affiliations

Abstract

Despite effective antiretroviral therapy (ART), HIV infected individuals throughout the world remain at significant risk of respiratory infections and non-communicable disease. Severe disease from SARS-CoV-2 is associated with a hyperinflammatory phenotype which manifests in the lungs as pneumonia and in some cases can lead to acute respiratory failure. Progression to severe COVID-19 is associated with comorbid disease such as obesity, diabetes mellitus and cardiovascular disease, however data concerning the associated risks of HIV coinfection are still conflicting, with large population studies demonstrating poorer outcomes, whilst smaller, case-controlled studies showing better outcomes. Furthermore, underlying immunopathological processes within the lungs and elsewhere, including interactions with other opportunistic infections (OI), remain largely undefined. Nonetheless, new and repurposed anti-viral therapies and vaccines which have been developed are safe to use in this population, and anti-inflammatory agents are recommended with the caveat that the coexistence of opportunistic infections is considered and excluded. Finally, HIV infected patients remain reliant on good ART adherence practices to maintain HIV viral suppression, and some of these practices were disrupted during the COVID-19 pandemic, putting these patients at further risk for acute and long-term adverse outcomes.



Publication History

Article published online:
16 January 2023

© 2023. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 
  • References

  • 1 UNAIDS. UNAIDS DATA. Accessed March 21, 2022 at: https://www.unaids.org/sites/default/files/media_asset/JC3032_AIDS_Data_book_2021_En.pdf
  • 2 Cucinotta D, Vanelli M. WHO declares COVID-19 a pandemic. Acta Biomed 2020; 91 (01) 157-160
  • 3 Zhu Z, Lian X, Su X, Wu W, Marraro GA, Zeng Y. From SARS and MERS to COVID-19: a brief summary and comparison of severe acute respiratory infections caused by three highly pathogenic human coronaviruses. Respir Res 2020; 21 (01) 224
  • 4 Roos R. Center for Infectious Disease Research and Policy. Estimates of SARS death rates revised upwards. Accessed March 28, 2022 at: https://www.cidrap.umn.edu/news-perspective/2003/05/estimates-sars-death-rates-revised-upward
  • 5 World Health Organisation Middle East respiratory syndrome coronavirus (MERS-CoV). Accessed March 28, 2022 at: https://www.who.int/health-topics/middle-east-respiratory-syndrome-coronavirus-mers#tab=tab_1
  • 6 Leung GM, Hedley AJ, Ho LM. et al. The epidemiology of severe acute respiratory syndrome in the 2003 Hong Kong epidemic: an analysis of all 1755 patients. Ann Intern Med 2004; 141 (09) 662-673
  • 7 Hui DS, Azhar EI, Kim YJ, Memish ZA, Oh MD, Zumla A. Middle East respiratory syndrome coronavirus: risk factors and determinants of primary, household, and nosocomial transmission. Lancet Infect Dis 2018; 18 (08) e217-e227
  • 8 Wong AT, Tsang OT, Wong MY. et al; PMH SARS Study Group. Coronavirus infection in an AIDS patient. AIDS 2004; 18 (05) 829-830
  • 9 Feikin DR, Feldman C, Schuchat A, Janoff EN. Global strategies to prevent bacterial pneumonia in adults with HIV disease. Lancet Infect Dis 2004; 4 (07) 445-455
  • 10 Kohli R, Lo Y, Homel P. et al; HER Study Group. Bacterial pneumonia, HIV therapy, and disease progression among HIV-infected women in the HIV epidemiologic research (HER) study. Clin Infect Dis 2006; 43 (01) 90-98
  • 11 Grau I, Pallares R, Tubau F. et al; Spanish Pneumococcal Infection Study Network (G03/103). Epidemiologic changes in bacteremic pneumococcal disease in patients with human immunodeficiency virus in the era of highly active antiretroviral therapy. Arch Intern Med 2005; 165 (13) 1533-1540
  • 12 Cohen C, Simonsen L, Sample J. et al. Influenza-related mortality among adults aged 25-54 years with AIDS in South Africa and the United States of America. Clin Infect Dis 2012; 55 (07) 996-1003
  • 13 Park DR, Sherbin VL, Goodman MS. et al; Harborview CAP Study Group. The etiology of community-acquired pneumonia at an urban public hospital: influence of human immunodeficiency virus infection and initial severity of illness. J Infect Dis 2001; 184 (03) 268-277
  • 14 Feldman C, Klugman KP, Yu VL. et al; International Pneumococcal Study Group. Bacteraemic pneumococcal pneumonia: impact of HIV on clinical presentation and outcome. J Infect 2007; 55 (02) 125-135
  • 15 Hirschtick RE, Glassroth J, Jordan MC. et al; Pulmonary Complications of HIV Infection Study Group. Bacterial pneumonia in persons infected with the human immunodeficiency virus. N Engl J Med 1995; 333 (13) 845-851
  • 16 Dworkin MS, Ward JW, Hanson DL, Jones JL, Kaplan JE. Adult and Adolescent Spectrum of HIV Disease Project. Pneumococcal disease among human immunodeficiency virus-infected persons: incidence, risk factors, and impact of vaccination. Clin Infect Dis 2001; 32 (05) 794-800
  • 17 Mane A, Gujar P, Gaikwad S. et al. Aetiological spectrum of severe community-acquired pneumonia in HIV-positive patients from Pune, India. Indian J Med Res 2018; 147 (02) 202-206
  • 18 Kiragga AN, Mubiru F, Kambugu AD, Kamya MR, Castelnuovo B. A decade of antiretroviral therapy in Uganda: what are the emerging causes of death?. BMC Infect Dis 2019; 19 (01) 77
  • 19 Schouten J, Wit FW, Stolte IG. et al; AGEhIV Cohort Study Group. Cross-sectional comparison of the prevalence of age-associated comorbidities and their risk factors between HIV-infected and uninfected individuals: the AGEhIV cohort study. Clin Infect Dis 2014; 59 (12) 1787-1797
  • 20 Guaraldi G, Orlando G, Zona S. et al. Premature age-related comorbidities among HIV-infected persons compared with the general population. Clin Infect Dis 2011; 53 (11) 1120-1126
  • 21 Science Brief CDC. Evidence used to Update the List of Underlying Medical Conditions Associated with High Risk for Severe COVID-19. Accessed 28 March, 2022 at: https://www.cdc.gov/coronavirus/2019-ncov/science/science-briefs/underlying-evidence-table.html#:~:text=Asthma%2C%20blood%20disorders%2C%20cancer%2C,medications%2C%20solid%20organ%20or%20blood
  • 22 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 (02) 157-168
  • 23 Appay V, Sauce D. Immune activation and inflammation in HIV-1 infection: causes and consequences. J Pathol 2008; 214 (02) 231-241
  • 24 Hunt PW, Lee SA, Siedner MJ. Immunologic biomarkers, morbidity, and mortality in treated HIV infection. J Infect Dis 2016; 214 (Suppl. 02) S44-S50
  • 25 Western Cape Department of Health in collaboration with the National Institute for Communicable Diseases, South Africa. 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 (07) e2005-e2015
  • 26 Bhaskaran K, Rentsch CT, MacKenna B. 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 (01) e24-e32
  • 27 Hadi YB, Naqvi SFZ, Kupec JT, Sarwari AR. Characteristics and outcomes of COVID-19 in patients with HIV: a multicentre research network study. AIDS 2020; 34 (13) F3-F8
  • 28 Ho HE, Peluso MJ, Margus C. et al. Clinical outcomes and immunologic characteristics of coronavirus disease 2019 in people with human immunodeficiency virus. J Infect Dis 2021; 223 (03) 403-408
  • 29 Miyashita H, Kuno T. Prognosis of coronavirus disease 2019 (COVID-19) in patients with HIV infection in New York City. HIV Med 2021; 22 (01) e1-e2
  • 30 Härter G, Spinner CD, Roider J. et al. COVID-19 in people living with human immunodeficiency virus: a case series of 33 patients. Infection 2020; 48 (05) 681-686
  • 31 Vizcarra P, Pérez-Elías MJ, Quereda C. et al; COVID-19 ID Team. Description of COVID-19 in HIV-infected individuals: a single-centre, prospective cohort. Lancet HIV 2020; 7 (08) e554-e564
  • 32 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
  • 33 de Wilde AH, Jochmans D, Posthuma CC. et al. Screening of an FDA-approved compound library identifies four small-molecule inhibitors of Middle East respiratory syndrome coronavirus replication in cell culture. Antimicrob Agents Chemother 2014; 58 (08) 4875-4884
  • 34 Corleis B, Bucsan AN, Deruaz M. et al. HIV-1 and SIV infection are associated with early loss of lung interstitial CD4+ T cells and dissemination of pulmonary tuberculosis. Cell Rep 2019; 26 (06) 1409-1418.e5
  • 35 Li Y, Kang G, Duan L. et al. SIV infection of lung macrophages. PLoS One 2015; 10 (05) e0125500
  • 36 Alexandrova Y, Costiniuk CT, Jenabian MA. Pulmonary immune dysregulation and viral persistence during HIV infection. Front Immunol 2022; 12: 808722
  • 37 Jambo KC, Sepako E, Fullerton DG. et al. Bronchoalveolar CD4+ T cell responses to respiratory antigens are impaired in HIV-infected adults. Thorax 2011; 66 (05) 375-382
  • 38 Neff CP, Chain JL, MaWhinney S. et al. Lymphocytic alveolitis is associated with the accumulation of functionally impaired HIV-specific T cells in the lung of antiretroviral therapy-naive subjects. Am J Respir Crit Care Med 2015; 191 (04) 464-473
  • 39 Popescu I, Drummond MB, Gama L. et al. HIV suppression restores the lung mucosal CD4+ T-cell viral immune response and resolves CD8+ T-cell alveolitis in patients at risk for HIV-associated chronic obstructive pulmonary disease. J Infect Dis 2016; 214 (10) 1520-1530
  • 40 Cribbs SK, Lennox J, Caliendo AM, Brown LA, Guidot DM. Healthy HIV-1-infected individuals on highly active antiretroviral therapy harbor HIV-1 in their alveolar macrophages. AIDS Res Hum Retroviruses 2015; 31 (01) 64-70d
  • 41 Cribbs SK, Crothers K, Morris A. Pathogenesis of HIV-related lung disease: immunity, infection, and inflammation. Physiol Rev 2020; 100 (02) 603-632
  • 42 Agostini C, Trentin L, Zambello R, Semenzato G. HIV-1 and the lung. Infectivity, pathogenic mechanisms, and cellular immune responses taking place in the lower respiratory tract. Am Rev Respir Dis 1993; 147 (04) 1038-1049
  • 43 Tachado SD, Zhang J, Zhu J, Patel N, Koziel H. HIV impairs TNF-alpha release in response to Toll-like receptor 4 stimulation in human macrophages in vitro. Am J Respir Cell Mol Biol 2005; 33 (06) 610-621
  • 44 Wheatley AK, Kristensen AB, Lay WN, Kent SJ. HIV-dependent depletion of influenza-specific memory B cells impacts B cell responsiveness to seasonal influenza immunisation. Sci Rep 2016; 6: 26478
  • 45 Moir S, Ho J, Malaspina A. et al. Evidence for HIV-associated B cell exhaustion in a dysfunctional memory B cell compartment in HIV-infected viremic individuals. J Exp Med 2008; 205 (08) 1797-1805
  • 46 Brune KA, Ferreira F, Mandke P. et al. HIV Impairs lung epithelial integrity and enters the epithelium to promote chronic lung inflammation. PLoS One 2016; 11 (03) e0149679
  • 47 Perlman S, Dandekar AA. Immunopathogenesis of coronavirus infections: implications for SARS. Nat Rev Immunol 2005; 5 (12) 917-927
  • 48 Tomar B, Anders HJ, Desai J, Mulay SR. Neutrophils and neutrophil extracellular traps drive necroinflammation in COVID-19. Cells 2020; 9 (06) E1383
  • 49 Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin Immunopathol 2017; 39 (05) 529-539
  • 50 Jafarzadeh A, Chauhan P, Saha B, Jafarzadeh S, Nemati M. Contribution of monocytes and macrophages to the local tissue inflammation and cytokine storm in COVID-19: lessons from SARS and MERS, and potential therapeutic interventions. Life Sci 2020; 257: 118102
  • 51 Mathew D, Giles JR, Baxter AE. et al; UPenn COVID Processing Unit. Deep immune profiling of COVID-19 patients reveals distinct immunotypes with therapeutic implications. Science 2020; 369 (6508): eabc8511
  • 52 Huang C, Wang Y, Li X. et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395 (10223): 497-506
  • 53 Chen Z, John Wherry E. T cell responses in patients with COVID-19. Nat Rev Immunol 2020; 20 (09) 529-536
  • 54 Diao B, Wang C, Tan Y. et al. Reduction and functional exhaustion of T Cells in patients with coronavirus disease 2019 (COVID-19). Front Immunol 2020; 11: 827
  • 55 Zhao J, Yuan Q, Wang H. et al. Antibody responses to SARS-CoV-2 in patients with novel coronavirus disease 2019. Clin Infect Dis 2020; 71 (16) 2027-2034
  • 56 Bergamaschi L, Mescia F, Turner L. et al; Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID BioResource Collaboration. Longitudinal analysis reveals that delayed bystander CD8+ T cell activation and early immune pathology distinguish severe COVID-19 from mild disease. Immunity 2021; 54 (06) 1257-1275.e8
  • 57 Moss P. The T cell immune response against SARS-CoV-2. Nat Immunol 2022; 23 (02) 186-193
  • 58 Riou C, du Bruyn E, Stek C. et al; HIATUS consortium. Relationship of SARS-CoV-2-specific CD4 response to COVID-19 severity and impact of HIV-1 and tuberculosis coinfection. J Clin Invest 2021; 131 (12) 149125
  • 59 Gallais F, Velay A, Nazon C. et al. Intrafamilial exposure to SARS-CoV-2 associated with cellular immune response without seroconversion, France. Emerg Infect Dis 2021;27(01):
  • 60 Venet F, Gossez M, Bidar F. et al; RICO study group. T cell response against SARS-CoV-2 persists after one year in patients surviving severe COVID-19. EBioMedicine 2022; 78: 103967
  • 61 Westblade LF, Brar G, Pinheiro LC. et al. SARS-CoV-2 viral load predicts mortality in patients with and without cancer who are hospitalized with COVID-19. Cancer Cell 2020; 38 (05) 661-671.e2
  • 62 Jacobs JL, Bain W, Naqvi A. et al. SARS-CoV-2 viremia is associated with COVID-19 severity and predicts clinical outcomes. Clin Infect Dis 2021; 74 (09) 1525-1533
  • 63 Fajnzylber J, Regan J, Coxen K. et al; Massachusetts Consortium for Pathogen Readiness. SARS-CoV-2 viral load is associated with increased disease severity and mortality. Nat Commun 2020; 11 (01) 5493
  • 64 Liu Y, Xiao Y, Wu S. et al. People living with HIV easily lose their immune response to SARS-CoV-2: result from a cohort of COVID-19 cases in Wuhan, China. BMC Infect Dis 2021; 21 (01) 1029
  • 65 Mondi A, Cimini E, Colavita F. et al. COVID-19 in people living with HIV: clinical implications of dynamics of the immune response to SARS-CoV-2. J Med Virol 2021; 93 (03) 1796-1804
  • 66 Yamamoto S, Saito M, Nagai E. et al. Antibody response to SARS-CoV-2 in people living with HIV. J Microbiol Immunol Infect 2021; 54 (01) 144-146
  • 67 Pallikkuth S, Sharkey M, Beauchamps L. et al. Persistence of SARS-CoV-2-specific AB response in HIV+ individuals on art. Top Antivir Med 2021; 29 (01) 88
  • 68 Snyman J, Hwa SH, Krause R. et al. Similar antibody responses against SARS-CoV-2 in HIV uninfected and infected individuals on antiretroviral therapy during the first South African infection wave. Clin Infect Dis 2021; (e-pub ahead of print) DOI: 10.1093/cid/ciab758.
  • 69 Alcaide ML, Nogueira NF, Salazar AS. et al. A longitudinal analysis of SARS-CoV-2 antibody responses among people with HIV. Front Med (Lausanne) 2022; 9: 768138
  • 70 Joosten SA, van Meijgaarden KE, Del Nonno F. et al. Patients with tuberculosis have a dysfunctional circulating B-Cell compartment, which normalizes following successful treatment. PLoS Pathog 2016; 12 (06) e1005687
  • 71 Sharov KS. HIV/SARS-CoV-2 co-infection: T cell profile, cytokine dynamics and role of exhausted lymphocytes. Int J Infect Dis 2021; 102: 163-169
  • 72 Hu R, Yan H, Liu M. et al. Brief report: virologic and immunologic outcomes for HIV patients with coronavirus disease 2019. J Acquir Immune Defic Syndr 2021; 86 (02) 213-218
  • 73 Petrone L, Petruccioli E, Vanini V. et al. Coinfection of tuberculosis and COVID-19 limits the ability to in vitro respond to SARS-CoV-2. Int J Infect Dis 2021; 113 (Suppl. 01) S82-S87
  • 74 Huang J, Xie N, Hu X. et al. Epidemiological, virological and serological features of coronavirus disease 2019 (COVID-19) cases in people living with human immunodeficiency virus in Wuhan: a population-based cohort study. Clin Infect Dis 2021; 73 (07) e2086-e2094
  • 75 Docherty AB, Harrison EM, Green CA. et al; ISARIC4C investigators. Features of 20 133 UK patients in hospital with COVID-19 using the ISARIC WHO clinical characterisation protocol: prospective observational cohort study. BMJ 2020; 369: m1985
  • 76 Jassat W, Cohen C, Tempia S. et al; DATCOV author group. Risk factors for COVID-19-related in-hospital mortality in a high HIV and tuberculosis prevalence setting in South Africa: a cohort study. Lancet HIV 2021; 8 (09) e554-e567
  • 77 Blanco JL, Ambrosioni J, Garcia F. et al; COVID-19 in HIV Investigators. COVID-19 in patients with HIV: clinical case series. Lancet HIV 2020; 7 (05) e314-e316
  • 78 Shalev N, Scherer M, LaSota ED. et al. Clinical characteristics and outcomes in people living with human immunodeficiency virus hospitalized for coronavirus disease 2019. Clin Infect Dis 2020; 71 (16) 2294-2297
  • 79 Calza L, Bon I, Tadolini M. et al. COVID-19 in patients with HIV-1 infection: a single-centre experience in northern Italy. Infection 2021; 49 (02) 333-337
  • 80 Charre C, Icard V, Pradat P. et al. Coronavirus disease 2019 attack rate in HIV-infected patients and in preexposure prophylaxis users. AIDS 2020; 34 (12) 1765-1770
  • 81 Park L, Rentsch C, Sigel K. et al. COVID-19 in the largest US HIV Cohort. presented at: International AIDS Conference 2020. Accessed March 22, 2022 at: https://www.natap.org/2020/IAC/IAC_115.htm
  • 82 Del Amo J, Polo R, Moreno S. et al; The Spanish HIV/COVID-19 Collaboration. Incidence and severity of COVID-19 in HIV-positive persons receiving antiretroviral therapy: a cohort study. Ann Intern Med 2020; 173 (07) 536-541
  • 83 Inciarte A, Gonzalez-Cordon A, Rojas J. et al; (on behalf the COVID-19 in HIV Investigators). 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 (12) 1775-1780
  • 84 Sachdev D, Mara E, Hsu L. et al. COVID-19 susceptibility and outcomes among people living with HIV in San Francisco. J Acquir Immune Defic Syndr 2021; 86 (01) 19-21
  • 85 Meyerowitz EA, Kim AY, Ard KL. et al. Disproportionate burden of coronavirus disease 2019 among racial minorities and those in congregate settings among a large cohort of people with HIV. AIDS 2020; 34 (12) 1781-1787
  • 86 Childs K, Post FA, Norcross C. et al. Hospitalized patients with COVID-19 and human immunodeficiency virus: a case series. Clin Infect Dis 2020; 71 (08) 2021-2022
  • 87 Khunti K, Singh AK, Pareek M, Hanif W. Is ethnicity linked to incidence or outcomes of COVID-19?. BMJ 2020; 369: m1548
  • 88 Batty GD, Gaye B, Gale CR, Hamer M, Lassale C. Explaining ethnic disparities in COVID-19 mortality: population-based, prospective cohort study. medRxiv 2021; DOI: 10.1101/2021.02.07.21251079.
  • 89 Luan H, Song I, Fiellin DA, Ransome Y. HIV infection prevalence significantly intersects with COVID-19 infection at the area level: a US county-level analysis. J Acquir Immune Defic Syndr 2021; 88 (02) 125-131
  • 90 Geretti AM, Stockdale AJ, Kelly SH. 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 (07) e2095-e2106
  • 91 Byrd KM, Beckwith CG, Garland JM. et al. SARS-CoV-2 and HIV coinfection: clinical experience from Rhode Island, United States. J Int AIDS Soc 2020; 23 (07) e25573
  • 92 Karmen-Tuohy S, Carlucci PM, Zervou FN. et al. Outcomes among HIV-positive patients hospitalized with COVID-19. J Acquir Immune Defic Syndr 2020; 85 (01) 6-10
  • 93 Sigel K, Swartz T, Golden E. et al. Coronavirus 2019 and people living with human immunodeficiency virus: outcomes for hospitalized patients in New York City. Clin Infect Dis 2020; 71 (11) 2933-2938
  • 94 Ceballos ME, Ross P, Lasso M. et al; Chilean HIV/COVID-19 Study Group. Clinical characteristics and outcomes of people living with HIV hospitalized with COVID-19: a nationwide experience. Int J STD AIDS 2021; 32 (05) 435-443
  • 95 Lee MJ, Snell LB, Douthwaite ST. 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 (02) 121-133
  • 96 Bertagnolio S, Thwin SS, Silva R. 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 (07) e486-e495
  • 97 Del Amo J, Polo R, Moreno S. et al. Antiretrovirals and risk of COVID-19 diagnosis and hospitalization in HIV-positive persons. Epidemiology 2020; 31 (06) e49-e51
  • 98 Gagliardini R, Vergori A, Lorenzini P. et al. Characteristics and outcomes of COVID-19-related hospitalization among PLWH. J Clin Med 2022; 11 (06) 1546
  • 99 Gervasoni C, Meraviglia P, Riva A. et al. Clinical features and outcomes of patients with human immunodeficiency virus with COVID-19. Clin Infect Dis 2020; 71 (16) 2276-2278
  • 100 Nomah DK, Reyes-Urueña J, Díaz Y. et al; PISCIS study group. Sociodemographic, clinical, and immunological factors associated with SARS-CoV-2 diagnosis and severe COVID-19 outcomes in people living with HIV: a retrospective cohort study. Lancet HIV 2021; 8 (11) e701-e710
  • 101 Rodés B, Cadiñanos J, Esteban-Cantos A, Rodríguez-Centeno J, Arribas JR. Ageing with HIV: challenges and biomarkers. EBioMedicine 2022; 77: 103896
  • 102 Desai S, Landay A. Early immune senescence in HIV disease. Curr HIV/AIDS Rep 2010; 7 (01) 4-10
  • 103 Smith RL, de Boer R, Brul S, Budovskaya Y, van Spek H. Premature and accelerated aging: HIV or HAART?. Front Genet 2013; 3: 328
  • 104 Zhou F, Yu T, Du R. et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020; 395 (10229): 1054-1062
  • 105 Venturas J, Zamparini J, Shaddock E. et al. Comparison of outcomes in HIV-positive and HIV-negative patients with COVID-19. J Infect 2021; 83 (02) 217-227
  • 106 Mellor MM, Bast AC, Jones NR. et al. Risk of adverse coronavirus disease 2019 outcomes for people living with HIV. AIDS 2021; 35 (04) F1-F10
  • 107 Hariyanto TI, Rosalind J, Christian K, Kurniawan A. Human immunodeficiency virus and mortality from coronavirus disease 2019: a systematic review and meta-analysis. South Afr J HIV Med 2021; 22 (01) 1220
  • 108 Wang Y, Feng R, Xu J, Shi L, Feng H, Yang H. An updated meta-analysis on the association between HIV infection and COVID-19 mortality. AIDS 2021; 35 (11) 1875-1878
  • 109 Danwang C, Noubiap JJ, Robert A, Yombi JC. Outcomes of patients with HIV and COVID-19 co-infection: a systematic review and meta-analysis. AIDS Res Ther 2022; 19 (01) 3
  • 110 Liverpool University COVID-19 Drug Interactions. Available at. Accessed May 30, 2022 at: https://www.covid19-druginteractions.org/
  • 111 Special considerations NIH in people with HIV. Accessed May 26, 2022 at: https://www.covid19treatmentguidelines.nih.gov/special-populations/hiv/
  • 112 AstraZeneca Food and Drug Administration Drug Sheet for Healthcare providers: Emergency Use Authorisation for Evushield™ (tixagevimab co-packaged with cilgavimab). Accessed 26 May, 2022 at: https://www.fda.gov/media/154701/download
  • 113 AstraZeneca. New analyses of two AZD7442 COVID-19 Phase III trials in high-risk populations confirm robust efficacy and long-term prevention. Accessed 26 May, 2022 at: https://www.astrazeneca.com/media-centre/press-releases/2021/new-analyses-of-two-azd7442-covid-19-phase-iii-trials-in-high-risk-populations-confirm-robust-efficacy-and-long-term-prevention.html
  • 114 Mahase E. Covid-19: AstraZeneca says its antibody drug AZD7442 is effective for preventing and reducing severe illness. BMJ 2021; 375 (2860): n2860
  • 115 Levin MJ, Ustianowski A, De Wit S. et al; PROVENT Study Group. Intramuscular AZD7442 (tixagevimab-cilgavimab) for prevention of Covid-19. N Engl J Med 2022; 386 (23) 2188-2200
  • 116 Chavda VP, Prajapati R, Lathigara D. et al. Therapeutic monoclonal antibodies for COVID-19 management: an update. Expert Opin Biol Ther 2022; 22 (06) 763-780
  • 117 Westendorf K, Žentelis S, Wang L. et al. LY-CoV1404 (bebtelovimab) potently neutralizes SARS-CoV-2 variants. Cell Rep 2022; 39 (07) 110812
  • 118 Hammond J, Leister-Tebbe H, Gardner A. et al; EPIC-HR Investigators. Oral nirmatrelvir for high-risk, nonhospitalized adults with Covid-19. N Engl J Med 2022; 386 (15) 1397-1408
  • 119 Marzolini C, Kuritzkes DR, Marra F. et al. Recommendations for the management of drug-drug interactions between the COVID-19 antiviral nirmatrelvir/ritonavir (Paxlovid). Clin Pharmacol Ther 2022
  • 120 Pfizer. Fact sheet for healthcare providers: Emergency use authorization for Paxlovid™. Accessed 26 May, 2022 at: https://www.fda.gov/media/155050/download
  • 121 IDSA. Paxlovid for the Treatment of COVID-19: Considerations for People With HIV and Hepatitis C. Accessed May 26, 2022at: https://www.idsociety.org/globalassets/covid-19-real-time-learning-network/patient-populations/hiv/oral-covid-tx-considerations-for-people-with-hiv-and-hcv.pdf
  • 122 Beigel JH, Tomashek KM, Dodd LE. et al; ACTT-1 Study Group Members. Remdesivir for the treatment of Covid-19—final report. N Engl J Med 2020; 383 (19) 1813-1826
  • 123 Jayk Bernal A, Gomes da Silva MM, Musungaie DB. et al; MOVe-OUT Study Group. Molnupiravir for oral treatment of Covid-19 in nonhospitalized patients. N Engl J Med 2022; 386 (06) 509-520
  • 124 Walimbwa SI, Kaboggoza JP, Waitt C, Byakika-Kibwika P, D'Avolio A, Lamorde M. An open-label, randomized, single intravenous dosing study to investigate the effect of fixed-dose combinations of tenofovir/lamivudine or atazanavir/ritonavir on the pharmacokinetics of remdesivir in Ugandan healthy volunteers (RemTLAR). Trials 2021; 22 (01) 831
  • 125 BHIVA. British HIV Association update on COVID treatments for people with HIV. Accessed 26 May, 2022 at: https://www.bhiva.org/update-on-COVID-treatments-for-people-with-HIV
  • 126 RECOVERY Collaborative Group. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet 2021; 397 (10285): 1637-1645
  • 127 Gordon AC, Mouncey PR, Al-Beidh F. et al; REMAP-CAP Investigators. Interleukin-6 receptor antagonists in critically ill patients with Covid-19. N Engl J Med 2021; 384 (16) 1491-1502
  • 128 Horby P, Lim WS, Emberson JR. et al; RECOVERY Collaborative Group. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med 2021; 384 (08) 693-704
  • 129 Kalil AC, Patterson TF, Mehta AK. et al; ACTT-2 Study Group Members. Baricitinib plus remdesivir for hospitalized adults with Covid-19. N Engl J Med 2021; 384 (09) 795-807
  • 130 Kmietowicz Z. Covid-19: WHO recommends baricitinib and sotrovimab to treat patients. BMJ 2022; 376: o97
  • 131 Gutierrez MDM, Mur I, Mateo MG, Vidal F, Domingo P. Pharmacological considerations for the treatment of COVID-19 in people living with HIV (PLWH). Expert Opin Pharmacother 2021; 22 (09) 1127-1141
  • 132 Minkove SJ, Geiger G, Llibre JM. et al; HIV-COVID-19 Consortium. Clinical outcomes after IL-6 blockade in patients with COVID-19 and HIV: a case series. AIDS Res Ther 2022; 19 (01) 6
  • 133 Marconi VC, Moser C, Gavegnano C. et al. Randomized trial of ruxolitinib in antiretroviral-treated adults with human immunodeficiency virus. Clin Infect Dis 2022; 74 (01) 95-104
  • 134 Gálvez Acosta S, Javalera Rincón M. Ruxolitinib as first-line therapy in secondary hemophagocytic lymphohistiocytosis and HIV infection. Int J Hematol 2020; 112 (03) 418-421
  • 135 World Health Organisation. Coronavirus disease (COVID-19): COVID-19 vaccines and people living with HIV. Internet Updated 14 July 2021. Accessed 31 May, 2022 at: https://www.who.int/news-room/questions-and-answers/item/coronavirus-disease-(covid-19)-covid-19-vaccines-and-people-living-with-hiv#
  • 136 Polack FP, Thomas SJ, Kitchin N. et al; C4591001 Clinical Trial Group. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med 2020; 383 (27) 2603-2615
  • 137 Sadoff J, Gray G, Vandebosch A. et al; ENSEMBLE Study Group. Safety and efficacy of single-dose Ad26.COV2.S vaccine against Covid-19. N Engl J Med 2021; 384 (23) 2187-2201
  • 138 Baden LR, El Sahly HM, Essink B. et al; COVE Study Group. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med 2021; 384 (05) 403-416
  • 139 Frater J, Ewer KJ, Ogbe A. et al; Oxford COVID Vaccine Trial Group. Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 in HIV infection: a single-arm substudy of a phase 2/3 clinical trial. Lancet HIV 2021; 8 (08) e474-e485
  • 140 Madhi SA, Koen AL, Izu A. et al; Wits VIDA COVID team. Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 in people living with and without HIV in South Africa: an interim analysis of a randomised, double-blind, placebo-controlled, phase 1B/2A trial. Lancet HIV 2021; 8 (09) e568-e580
  • 141 Oyaert M, De Scheerder MA, Van Herrewege S. et al. Evaluation of humoral and cellular responses in SARS-CoV-2 mRNA vaccinated immunocompromised patients. Front Immunol 2022; 13: 858399
  • 142 Ruddy JA, Boyarsky BJ, Bailey JR. et al. Safety and antibody response to two-dose SARS-CoV-2 messenger RNA vaccination in persons with HIV. AIDS 2021; 35 (14) 2399-2401
  • 143 Hassold N, Brichler S, Ouedraogo E. et al. Impaired antibody response to COVID-19 vaccination in advanced HIV infection. AIDS 2022; 36 (04) F1-F5
  • 144 Tau L, Turner D, Adler A. et al. SARS-CoV-2 humoral and cellular immune responses of patients with HIV after vaccination with BNT162b2 mRNA COVID-19 vaccine in the Tel-Aviv Medical Center. Open Forum Infect Dis 2022; 9 (04) ofac089
  • 145 Levy I, Wieder-Finesod A, Litchevsky V. et al. Immunogenicity and safety of the BNT162b2 mRNA COVID-19 vaccine in people living with HIV-1. Clin Microbiol Infect 2021; 27 (12) 1851-1855
  • 146 Tasker SA, O'Brien WA, Treanor JJ. et al. Effects of influenza vaccination in HIV-infected adults: a double-blind, placebo-controlled trial. Vaccine 1998; 16 (9-10): 1039-1042
  • 147 Poli G, Fauci AS. Cytokine modulation of HIV expression. Semin Immunol 1993; 5 (03) 165-173
  • 148 Spinelli MA, Peluso MJ, Lynch KL. et al. Differences in post-mRNA vaccination SARS-CoV-2 IgG concentrations and surrogate virus neutralization test response by HIV status and type of vaccine: a matched case-control observational study. Clin Infect Dis 2022; 75 (01) e916-e919
  • 149 Shinde V, Bhikha S, Hoosain Z. et al; 2019nCoV-501 Study Group. Efficacy of NVX-CoV2373 Covid-19 vaccine against the B.1.351 variant. N Engl J Med 2021; 384 (20) 1899-1909
  • 150 Netto LC, Ibrahim KY, Picone CM. et al. Safety and immunogenicity of CoronaVac in people living with HIV: a prospective cohort study. Lancet HIV 2022; 9 (05) e323-e331
  • 151 Sun J, Zheng Q, Madhira V. et al; National COVID Cohort Collaborative (N3C) Consortium. Association between immune dysfunction and COVID-19 breakthrough infection after SARS-CoV-2 vaccination in the US. JAMA Intern Med 2022; 182 (02) 153-162
  • 152 Coburn SB, Humes E, Lang R. et al. COVID-19 infections post-vaccination by HIV status in the United States. 2021 (e-pub ahead of print) DOI: 10.1101/2021.12.02.21267182
  • 153 Lin KY, Wu PY, Liu WD. et al. Effectiveness of COVID-19 vaccination among people living with HIV during a COVID-19 outbreak. J Microbiol Immunol Infect 2022; 55 (03) 535-539
  • 154 Buchbinder SP, Mehrotra DV, Duerr A. et al; Step Study Protocol Team. Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the step study): a double-blind, randomised, placebo-controlled, test-of-concept trial. Lancet 2008; 372 (9653): 1881-1893
  • 155 McElrath MJ, De Rosa SC, Moodie Z. et al; Step Study Protocol Team. HIV-1 vaccine-induced immunity in the test-of-concept step study: a case-cohort analysis. Lancet 2008; 372 (9653): 1894-1905
  • 156 Gray GE, Allen M, Moodie Z. et al; HVTN 503/Phambili study team. Safety and efficacy of the HVTN 503/Phambili study of a clade-B-based HIV-1 vaccine in South Africa: a double-blind, randomised, placebo-controlled test-of-concept phase 2b study. Lancet Infect Dis 2011; 11 (07) 507-515
  • 157 Frahm N, DeCamp AC, Friedrich DP. et al. Human adenovirus-specific T cells modulate HIV-specific T cell responses to an Ad5-vectored HIV-1 vaccine. J Clin Invest 2012; 122 (01) 359-367
  • 158 Perreau M, Pantaleo G, Kremer EJ. Activation of a dendritic cell-T cell axis by Ad5 immune complexes creates an improved environment for replication of HIV in T cells. J Exp Med 2008; 205 (12) 2717-2725
  • 159 Auclair S, Liu F, Niu Q. et al. Distinct susceptibility of HIV vaccine vector-induced CD4 T cells to HIV infection. PLoS Pathog 2018; 14 (02) e1006888
  • 160 Buchbinder SP, McElrath MJ, Dieffenbach C, Corey L. Use of adenovirus type-5 vectored vaccines: a cautionary tale. Lancet 2020; 396 (10260): e68-e69
  • 161 Logunov DY, Livermore DM, Ornelles DA. et al. COVID-19 vaccination and HIV-1 acquisition. Lancet 2022; 399 (10333): e34-e35
  • 162 Winning A, Nikolskaya P. South Africa regulator not authorising Russian COVID-19 vaccine for now. Reuters. Accessed March 22, 2022 at: https://www.reuters.com/world/africa/south-africa-regulator-not-authorising-russian-covid-19-vaccine-now-2021-10-18/
  • 163 Nyaungwa N, Devitt P. Namibia to suspend use of Russian COVID-19 vaccine - ministry. Reuters. Accessed March 22, 2022 at: https://www.reuters.com/world/africa/namibia-suspends-use-russian-covid-vaccine-after-safrica-flags-hiv-concerns-2021-10-23/
  • 164 IDSA. COVID-19 Real time learning network. HIV. Accessed May 30, 2022 at: https://www.idsociety.org/covid-19-real-time-learning-network/special-populations/hiv/
  • 165 Corsini Campioli C, Cano Cevallos E, Assi M, Patel R, Binnicker MJ, O'Horo JC. Clinical predictors and timing of cessation of viral RNA shedding in patients with COVID-19. J Clin Virol 2020; 130: 104577 d
  • 166 Yousaf M, Hameed M, Alsoub H, Khatib M, Jamal W, Ahmad M. COVID-19: prolonged viral shedding in an HIV patient with literature review of risk factors for prolonged viral shedding and its implications for isolation strategies. Clin Case Rep 2021; 9 (03) 1397-1401
  • 167 Tan AT, Linster M, Tan CW. et al. Early induction of functional SARS-CoV-2-specific T cells associates with rapid viral clearance and mild disease in COVID-19 patients. Cell Rep 2021; 34 (06) 108728
  • 168 Maponga TG, Jeffries M, Tegally H. et al. Persistent SARS-CoV-2 infection with accumulation of mutations in a patient with poorly controlled HIV infection. 2022; (e-pub ahead of print) DOI: 10.1093/cid/ciac548.
  • 169 Cele S, Karim F, Lustig G. et al; COMMIT-KZN Team. SARS-CoV-2 prolonged infection during advanced HIV disease evolves extensive immune escape. Cell Host Microbe 2022; 30 (02) 154-162.e5
  • 170 Hoffman SA, Costales C, Sahoo MK. et al. SARS-CoV-2 neutralization resistance mutations in patient with HIV/AIDS, California, USA. Emerg Infect Dis 2021; 27 (10) 2720-2723
  • 171 Karim F, Moosa M, Gosnell B. et al. Persistent SARS-CoV-2 infection and intra-host evolution in association with advanced HIV infection. medRxiv 2021; DOI: 10.1101/2021.06.03.21258228.
  • 172 Riddell AC, Kele B, Harris K. et al. Generation of novel SARS-CoV-2 variants on B.1.1.7 lineage in three patients with advanced HIV disease. Clin Infect Dis 2022; (e-pub ahead of print) DOI: 10.1093/cid/ciac409.
  • 173 da Silva Torres MK, Bichara CDA, de Almeida MNDS. et al. The complexity of SARS-CoV-2 infection and the COVID-19 pandemic. Front Microbiol 2022; 13: 789882
  • 174 Uzunova K, Filipova E, Pavlova V, Vekov T. Insights into antiviral mechanisms of remdesivir, lopinavir/ritonavir and chloroquine/hydroxychloroquine affecting the new SARS-CoV-2. Biomed Pharmacother 2020; 131: 110668
  • 175 Jain R, Mujwar S. Repurposing metocurine as main protease inhibitor to develop novel antiviral therapy for COVID-19. Struct Chem 2020; 31 (06) 2487-2499
  • 176 Liu X, Wang XJ. Potential inhibitors against 2019-nCoV coronavirus M protease from clinically approved medicines. J Genet Genomics 2020; 47 (02) 119-121
  • 177 Zhang XW, Yap YL. Old drugs as lead compounds for a new disease? Binding analysis of SARS coronavirus main proteinase with HIV, psychotic and parasite drugs. Bioorg Med Chem 2004; 12 (10) 2517-2521
  • 178 Rizza SA, Badley AD. HIV protease inhibitors impact on apoptosis. Med Chem 2008; 4 (01) 75-79
  • 179 Sheahan TP, Sims AC, Leist SR. et al. Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nat Commun 2020; 11 (01) 222
  • 180 Choy KT, Wong AY, Kaewpreedee P. et al. Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro. Antiviral Res 2020; 178: 104786
  • 181 Xie X, Muruato AE, Zhang X. et al. A nanoluciferase SARS-CoV-2 for rapid neutralization testing and screening of anti-infective drugs for COVID-19. Nat Commun 2020; 11 (01) 5214
  • 182 Yamamoto N, Yang R, Yoshinaka Y. et al. HIV protease inhibitor nelfinavir inhibits replication of SARS-associated coronavirus. Biochem Biophys Res Commun 2004; 318 (03) 719-725
  • 183 Jo S, Kim S, Yoo J, Kim MS, Shin DH. A study of 3CLpros as promising targets against SARS-CoV and SARS-CoV-2. Microorganisms 2021; 9 (04) 756
  • 184 Chu CM, Cheng VC, Hung IF. et al; HKU/UCH SARS Study Group. Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings. Thorax 2004; 59 (03) 252-256
  • 185 Musarrat F, Chouljenko V, Dahal A. et al. The anti-HIV drug nelfinavir mesylate (Viracept) is a potent inhibitor of cell fusion caused by the SARSCoV-2 spike (S) glycoprotein warranting further evaluation as an antiviral against COVID-19 infections. J Med Virol 2020; 92 (10) 2087-2095
  • 186 Chan JF, Yao Y, Yeung ML. et al. Treatment with lopinavir/ritonavir or interferon-β1b improves outcome of MERS-CoV infection in a nonhuman primate model of common marmoset. J Infect Dis 2015; 212 (12) 1904-1913
  • 187 Park SJ, Yu KM, Kim YI. et al. Antiviral efficacies of FDA-approved drugs against SARS-CoV-2 infection in ferrets. mBio 2020; 11 (03) DOI: 10.1128/mBio.01114-20.
  • 188 Abbvie C. Product Monograph Kaletra. Lopinavir/Ritonavir HIV protease inhibitor. Accessed April 4, 2022 at: https://www.abbvie.ca/content/dam/abbvie-dotcom/ca/en/documents/products/KALETRA_PM_EN.pdf
  • 189 Alvarez JC, Moine P, Davido B. et al; Garches COVID-19 Collaborative Group. Population pharmacokinetics of lopinavir/ritonavir in Covid-19 patients. Eur J Clin Pharmacol 2021; 77 (03) 389-397
  • 190 Lepage MA, Rozza N, Kremer R, Grunbaum A. Safety and effectiveness concerns of lopinavir/ritonavir in COVID-19 affected patients: a retrospective series. Clin Toxicol (Phila) 2021; 59 (07) 644-647
  • 191 Gregoire M, Le Turnier P, Gaborit BJ. et al. Lopinavir pharmacokinetics in COVID-19 patients. J Antimicrob Chemother 2020; 75 (09) 2702-2704
  • 192 Chan KS, Lai ST, Chu CM. et al. Treatment of severe acute respiratory syndrome with lopinavir/ritonavir: a multicentre retrospective matched cohort study. Hong Kong Med J 2003; 9 (06) 399-406
  • 193 Arabi YM, Asiri AY, Assiri AM. et al; Saudi Critical Care Trials Group. Interferon Beta-1b and lopinavir-ritonavir for Middle East Respiratory syndrome. N Engl J Med 2020; 383 (17) 1645-1656
  • 194 Qiu T, Liang S, Dabbous M, Wang Y, Han R, Toumi M. Chinese guidelines related to novel coronavirus pneumonia. J Mark Access Health Policy 2020; 8 (01) 1818446
  • 195 Cao B, Wang Y, Wen D. et al. A trial of lopinavir-ritonavir in adults hospitalized with severe Covid-19. N Engl J Med 2020; 382 (19) 1787-1799
  • 196 Carmona-Bayonas A, Jimenez-Fonseca P, Castañón E. A trial of lopinavir-ritonavir in Covid-19. N Engl J Med 2020; 382 (21) e68
  • 197 Hung IF, Lung KC, Tso EY. et al. Triple combination of interferon beta-1b, lopinavir-ritonavir, and ribavirin in the treatment of patients admitted to hospital with COVID-19: an open-label, randomised, phase 2 trial. Lancet 2020; 395 (10238): 1695-1704
  • 198 Kim JW, Kim EJ, Kwon HH. et al. Lopinavir-ritonavir versus hydroxychloroquine for viral clearance and clinical improvement in patients with mild to moderate coronavirus disease 2019. Korean J Intern Med (Korean Assoc Intern Med) 2021; 36 (1, suppl 1): S253-S263
  • 199 Yan D, Liu XY, Zhu YN. et al. Factors associated with prolonged viral shedding and impact of lopinavir/ritonavir treatment in hospitalised non-critically ill patients with SARS-CoV-2 infection. Eur Respir J 2020; 56 (01) 2000799
  • 200 Osborne V, Davies M, Lane S. et al. Lopinavir-ritonavir in the treatment of COVID-19: a dynamic systematic benefit-risk assessment. Drug Saf 2020; 43 (08) 809-821
  • 201 Dorward J, Gbinigie O, Cai T. et al. The protease inhibitor lopinavir, boosted with ritonavir, as treatment for COVID-19: a rapid review. Antivir Ther 2020; 25 (07) 365-376
  • 202 Lecronier M, Beurton A, Burrel S. et al. Comparison of hydroxychloroquine, lopinavir/ritonavir, and standard of care in critically ill patients with SARS-CoV-2 pneumonia: an opportunistic retrospective analysis. Crit Care 2020; 24 (01) 418
  • 203 Amani B, Khanijahani A, Amani B, Hashemi P. Lopinavir/ritonavir for COVID-19: a systematic review and meta-analysis. J Pharm Sci 2021; 24: 246-257
  • 204 RECOVERY Collaborative Group. Lopinavir-ritonavir in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet 2020; 396 (10259): 1345-1352
  • 205 Arabi YM, Gordon AC, Derde LPG. et al; REMAP-CAP Investigators. Lopinavir-ritonavir and hydroxychloroquine for critically ill patients with COVID-19: REMAP-CAP randomized controlled trial. Intensive Care Med 2021; 47 (08) 867-886
  • 206 Pan H, Peto R, Henao-Restrepo AM. et al; WHO Solidarity Trial Consortium. Repurposed antiviral drugs for Covid-19—interim WHO solidarity trial results. N Engl J Med 2021; 384 (06) 497-511
  • 207 Reis G, Moreira Silva EADS, Medeiros Silva DC. et al; TOGETHER Investigators. Effect of early treatment with hydroxychloroquine or lopinavir and ritonavir on risk of hospitalization among patients with COVID-19: the TOGETHER randomized clinical trial. JAMA Netw Open 2021; 4 (04) e216468
  • 208 Tan DHS, Chan AK, Jüni P. et al. Post-exposure prophylaxis against SARS-CoV-2 in close contacts of confirmed COVID-19 cases (CORIPREV): study protocol for a cluster-randomized trial. Trials 2021; 22 (01) 224
  • 209 Smit M, Marinosci A, Nicoletti GJ. et al. Efficacy of pragmatic same-day ring prophylaxis for adult individuals exposed to SARS-CoV-2 in Switzerland (COPEP): protocol of an open-label cluster randomised trial. BMJ Open 2020; 10 (11) e040110
  • 210 Ju J, Li X, Kumar S. et al. Nucleotide analogues as inhibitors of SARS-CoV Polymerase. Pharmacol Res Perspect 2020; 8 (06) e00674
  • 211 Elfiky AA. SARS-CoV-2 RNA dependent RNA polymerase (RdRp) targeting: an in silico perspective. J Biomol Struct Dyn 2021; 39 (09) 3204-3212
  • 212 Clososki GC, Soldi R, da Silva RM, Guaratini T, Lopes JN, Pereira P. Tenofovir Disoproxil Fumarate: New Chemical Developments and Encouraging in vitro Biological Results for SARS-CoV-2. J Brazil Chem Soc 2022; 31: 1552-1556
  • 213 Veras FP, Pontelli MC, Silva CM. et al. SARS-CoV-2-triggered neutrophil extracellular traps mediate COVID-19 pathology. J Exp Med 2020; 217 (12) e20201129
  • 214 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 (12) 3381-3386
  • 215 Biron CA, Gazzinelli RT. Effects of IL-12 on immune responses to microbial infections: a key mediator in regulating disease outcome. Curr Opin Immunol 1995; 7 (04) 485-496
  • 216 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 (04) 265-275
  • 217 Castillo-Mancilla JR, Meditz A, Wilson C. et al. Reduced immune activation during tenofovir-emtricitabine therapy in HIV-negative individuals. J Acquir Immune Defic Syndr 2015; 68 (05) 495-501
  • 218 Parienti JJ, Prazuck T, Peyro-Saint-Paul L. et al. Effect of tenofovir disoproxil fumarate and emtricitabine on nasopharyngeal SARS-CoV-2 viral load burden amongst outpatients with COVID-19: a pilot, randomized, open-label phase 2 trial. EClinicalMedicine 2021; 38: 100993
  • 219 Di Mascio M, Srinivasula S, Bhattacharjee A. et al. Antiretroviral tissue kinetics: in vivo imaging using positron emission tomography. Antimicrob Agents Chemother 2009; 53 (10) 4086-4095
  • 220 Twigg HL, Schnizlein-Bick CT, Weiden M. et al. Measurement of antiretroviral drugs in the lungs of HIV-infected patients. HIV Ther 2010; 4 (02) 247-251
  • 221 Lee WA, He GX, Eisenberg E. et al. Selective intracellular activation of a novel prodrug of the human immunodeficiency virus reverse transcriptase inhibitor tenofovir leads to preferential distribution and accumulation in lymphatic tissue. Antimicrob Agents Chemother 2005; 49 (05) 1898-1906
  • 222 Varga Z, Flammer AJ, Steiger P. et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet 2020; 395 (10234): 1417-1418
  • 223 Ayerdi O, Puerta T, Clavo P. et al; 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 (11) ofaa455
  • 224 Berenguer J, Díez C, Martín-Vicente M. et al. Prevalence and factors associated with SARS-CoV-2 seropositivity in the Spanish HIV Research Network Cohort. Clin Microbiol Infect 2021; 27 (11) 1678-1684
  • 225 Kang SH, Cho DH, Choi J, Baik SK, Gwon JG, Kim MY. Association between chronic hepatitis B infection and COVID-19 outcomes: a Korean nationwide cohort study. PLoS One 2021; 16 (10) e0258229
  • 226 Gaitán-Duarte HG, Álvarez-Moreno C, Rincón-Rodríguez CJ. et al. Effectiveness of rosuvastatin plus colchicine, emtricitabine/tenofovir and combinations thereof in hospitalized patients with COVID-19: a pragmatic, open-label randomized trial. EClinicalMedicine 2022; 43: 101242
  • 227 Goswami N, Fredriksen PM, Lundin KEA. et al. COVID-19 and its effects on endothelium in HIV-positive patients in sub-Saharan Africa: cardiometabolic risk, thrombosis and vascular function (ENDOCOVID STUDY). BMC Infect Dis 2021; 21 (01) 719
  • 228 Universidade Federal do Ceara. Clinical experimentation with tenofovir disoproxyl fumarate and emtricitabine for COVID-19 (ARTAN-C19). Accessed 28 June, 2022 at: https://clinicaltrials.gov/ct2/show/NCT04712357
  • 229 Instituto de Investigacion Hospital Univdersitario La Paz. Clinical trial to evaluate the efficacy of different treatments in patients with COVID-19. Accessed 28 July, 2022 at: https://clinicaltrials.gov/ct2/show/NCT04890626
  • 230 DeJong C, Spinelli MA, Okochi H, Gandhi M. Tenofovir-based PrEP for COVID-19: an untapped opportunity?. AIDS 2021; 35 (09) 1509-1511
  • 231 Nalbandian A, Sehgal K, Gupta A. et al. Post-acute COVID-19 syndrome. Nat Med 2021; 27 (04) 601-615
  • 232 Pujari S, Gaikwad S, Chitalikar A, Dabhade D, Joshi K, Bele V. Long-coronavirus disease among people living with HIV in western India: an observational study. Immun Inflamm Dis 2021; 9 (03) 1037-1043
  • 233 Mazzitelli M, Trunfio M, Sasset L. et al. Factors associated with severe COVID-19 and post-acute COVID-19 syndrome in a cohort of people living with HIV on antiretroviral treatment and with undetectable HIV RNA. Viruses 2022; 14 (03) 493
  • 234 Zulu JE, Banda D, Hines JZ. et al. Two-month follow-up of persons with SARS-CoV-2 infection-Zambia, September 2020: a cohort study. Pan Afr Med J 2022; 41: 26
  • 235 Peluso MJ, Spinelli MA, Deveau T-M. et al. Post-acute sequelae and adaptive immune responses in people living with HIV recovering from SARS-COV-2 Infection. 2022; 36 (12) F7-F16
  • 236 Jewell BL, Mudimu E, Stover J. et al; HIV Modelling Consortium. Potential effects of disruption to HIV programmes in sub-Saharan Africa caused by COVID-19: results from multiple mathematical models. Lancet HIV 2020; 7 (09) e629-e640
  • 237 Jiang H, Zhou Y, Tang W. Maintaining HIV care during the COVID-19 pandemic. Lancet HIV 2020; 7 (05) e308-e309
  • 238 World Health Organization. WHO: access to HIV medicines severely impacted by COVID-19 as AIDS response stalls. Accessed July 17, 2022 at: https://www.who.int/news/item/06-07-2020-who-access-to-hiv-medicines-severely-impacted-by-covid-19-as-aids-response-stalls
  • 239 Adugna A, Azanaw J, Sharew Melaku M. The effect of COVID-19 on routine HIV care services from health facilities in Northwest Ethiopia. HIV AIDS (Auckl) 2021; 13: 1159-1168
  • 240 Nyashanu M, Chireshe R, Mushawa F, Ekpenyong MS. Exploring the challenges of women taking antiretroviral treatment during the COVID-19 pandemic lockdown in peri-urban Harare, Zimbabwe. Int J Gynaecol Obstet 2021; 154 (02) 220-226
  • 241 Sanchez TH, Zlotorzynska M, Rai M, Baral SD. Characterizing the impact of COVID-19 on men who have sex with men across the United States in April, 2020. AIDS Behav 2020; 24 (07) 2024-2032
  • 242 Davey DLJ, Bekker LG, Mashele N, Gorbach P, Coates TJ, Myer L. PrEP retention and prescriptions for pregnant women during COVID-19 lockdown in South Africa. Lancet HIV 2020; 7 (11) e735
  • 243 Hong C, Horvath KJ, Stephenson R. et al. PrEP use and persistence among young sexual minority men 17-24 years old during the COVID-19 pandemic. AIDS Behav 2022; 26 (03) 631-638
  • 244 van Staden Q, Laurenzi CA, Toska E. Two years after lockdown: reviewing the effects of COVID-19 on health services and support for adolescents living with HIV in South Africa. J Int AIDS Soc 2022; 25 (04) e25904
  • 245 Rewari BB, Mangadan-Konath N, Sharma M. Impact of COVID-19 on the global supply chain of antiretroviral drugs: a rapid survey of Indian manufacturers. WHO South-East Asia J Public Health 2020; 9 (02) 126-133
  • 246 Dada DA, Aku E, David KB. COVID-19 pandemic and antiretrovirals (ARV) availability in Nigeria: recommendations to prevent shortages. Pan Afr Med J 2020; 35 (Suppl. 02) 149
  • 247 Benade M, Long L, Rosen S, Meyer-Rath G, Tucker JM, Miot J. Reduction in initiations of HIV treatment in South Africa during the COVID pandemic. BMC Health Serv Res 2022; 22 (01) 428
  • 248 Dorward J, Khubone T, Gate K. et al. The impact of the COVID-19 lockdown on HIV care in 65 South African primary care clinics: an interrupted time series analysis. Lancet HIV 2021; 8 (03) e158-e165
  • 249 World Health Organization Maintaining essential health services: operational guidance for the COVID-19 context, interim guidance, 1 June 2020. Accessed June 17, 2022 at: https://www.who.int/publications/i/item/WHO-2019-nCoV-essential_health_services-2020.2
  • 250 UNAIDS. Preventing HIV infections at the time of a new pandemic. Internet. Accessed June 16, 2022 at: https://www.unaids.org/en/resources/documents/2021/20210701_HIVPrevention_new_pandemic
  • 251 Linda N. South Africa hope its battle with HIV and TB helped prepare it for COVID-19. Science Insider. Internet. 7 April 2020. doi: 10.1126/science.abc1253 June 16, 2022. Accessed June 16, 2020 at: https://www.science.org/content/article/south-africa-hopes-its-battle-hiv-and-tb-helped-prepare-it-covid-19
  • 252 UNAIDS. UNAIDS and China working together during the COVID-19 outbreak to ensure that people living with HIV continue to get treatment. Accessed June 15, 2022 at: https://www.unaids.org/en/resources/presscentre/pressreleaseandstatementarchive/2020/february/20200218_china_covid19
  • 253 Abraham SA, Berchie GO, Doe PF, Agyare E, Addo SA, Obiri-Yeboah D. Effects of COVID-19 pandemic on ART Service delivery: perspectives of healthcare workers in a Teaching Hospital in Ghana. BMC Health Serv Res 2021; 21 (01) 1295
  • 254 Hoke T, Bateganya M, Toyo O. et al. How home delivery of antiretroviral drugs ensured uninterrupted HIV treatment during COVID-19: experiences from Indonesia, Laos, Nepal, and Nigeria. Glob Health Sci Pract 2021; 9 (04) 978-989
  • 255 Weerasuria M, Ko C, Ehm A. et al. The impact of the COVID-19 pandemic on people living with HIV in Victoria, Australia. AIDS Res Hum Retroviruses 2021; 37 (04) 322-328