AIDS AND COVID-19 ARE TWO PANDEMICS THAT AFFECT THE MOST VULNERABLE INDIVIDUALS: COVID-19 PATIENTS WITH HIV INFECTION HAVE A HIGHER RISK OF DEATH

Gaudelli F, Isufaj E, Qorri E. AIDS and COVID-19 are two pandemics that affect the most vulnerable individuals: COVID-19 patients with HIV infection have a higher risk of death. International Journal of Infection. 2023;7(2):56-60.

F. Gaudelli^1*, E. Isufaj² and E. Qorri²

¹ Department of Clinical and Experimental Medicine, University of Foggia, Italy;
² Dental School, Albanian University, Tirana, Albania.

*Correspondence to:
Dr. Federico Gaudelli,
Department of Clinical and Experimental Medicine,
University of Foggia,
Foggia, Italy.
e-mail: federico_gaudelli.563780@unifg.it

Received: 19 May, 2023 Accepted: 31 August, 2023

ISSN 1972-6945 [online] Copyright 2023 © by Biolife-publisher This publication and/or article is for individual use only and may not be further reproduced without written permission from the copyright holder. Unauthorized reproduction may result in financial and other penalties. Disclosure: all authors report no conflicts of interest relevant to this article.

ABSTRACT

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is responsible for COVID-19, a disease that has afflicted the global population. The human immunodeficiency virus (HIV) causes acquired immunodeficiency syndrome (AIDS), which has resulted in a global public health crisis with hundreds of millions of deaths. With the emergence of COVID-19 during the year 2019, these two pandemics overlapped, putting HIV-infected patients at a greater risk of severe COVID-19 and potential death. Several studies have been published examing the interactions between HIV and SARS-CoV-2, although some of them contradicted each other; the most common message was that HIV-positive patients who had COVID-19 became more severe than patients with COVID-19 alone, and have an increased risk of mortality from COVID-19. The two conditions had an effect that was not only additive, but sometimes synergistic. COVID-19 is more severe and more deadly in patients with HIV, regardless of HIV RNA level or CD4 cell count. This effect was also seen in people treated with antiretroviral therapy (ART). Additionally, a low CD4 lymphocyte count in HIV-infected patients is an important risk factor for the development of severe COVID-19. The COVID-19 vaccine has been important to prevent the deterioration and death of HIV patients.

KEYWORDS: AIDS, HIV, COVID-19, SARS-CoV-2, pandemic  

INTRODUCTION

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for COVID-19 disease which began with an outbreak in Wuhan, China in December of 2019. The disease rapidly spread around the world and resulted in the COVID-19 pandemic.

In the early stages of the pandemic, COVID-19 restrictions varied across different populations. To control the spread of SARS-CoV-2, many countries implemented measures like contact restrictions and self-isolation, leading to significant psychological distress, with a number of studies having demonstrated how the pandemic severely affected mental health and sleep quality (1). Wuhan, China, enforced a lockdown on January 23rd, 2020, followed by 30 provinces activating a first-level response (2).  These measures altered education, work, and lifestyle, with significant repercussions affecting university students, sleep habits, and mental comorbidity.

Human immunodeficiency virus (HIV) attacks the body’s immune system, specifically the CD4 cells (T cells), which help the immune system fight off infections (3). If not treated, HIV can lead to acquired immunodeficiency syndrome (AIDS) (4).

COVID-19 has been a significant public health pandemic which continues, with approximately 500 million confirmed cases in 2022 (5). At the same time, HIV has continued to circulate and infect enormous numbers of individuals, resulting in approximately 718,000 deaths in 2021, and amounting to approximately 40 million deaths to date (6). Table I provides a comparison of SARS-CoV-2 infection and HIV infection, discussing the routes of transmission, symptoms, diagnosis techniques, and modes of treatment for each infection (Table I).

Table I. Comparison of SARS-CoV-2 infection and HIV infection.

The two pandemics overlapped with the outbreak of COVID-19, and evidence has shown that people living with HIV suffered increased severity of COVID-19 (7,8). COVID-19 also caused a significant disruption in HIV health care access. During the pandemic, hospitalized HIV patients had problems getting treatment due to the high number of COVID-19 patients requesting hospitalization in infectious disease departments. This article discusses the COVID-19 and AIDS pandemics in terms of coinfection.

DISCUSSION

Studies have investigated patients with HIV and COVID-19 in order to establish the exact association between HIV infection and increased rates and severity of COVID-19 disease (9,10).  Some studies highlighted conflicting results, demonstrating that HIV infection and COVID-19 mortality were not associated, and there was a similar risk independent of HIV RNA level or CD4 cell count (11,12). However, there is substantial evidence that patients living with HIV are at higher risk for severe illness or mortality from COVID-19 compared to individuals without HIV (13,14).

Both HIV and SARS-CoV-2 affect the immune system, but in different ways. HIV directly targets the immune cells, while SARS-CoV-2 can cause an overreaction of the immune system leading to severe inflammation. Furthermore, people with HIV, especially those with untreated or advanced HIV, may be at higher risk for severe COVID-19. In addition, HIV-infected patients tend to worsen more easily and have increased comorbidity than non-infected individuals.

Managing HIV with antiretroviral therapy (ART) can improve the immune response and potentially reduce the severity of COVID-19, however other studies have shown increased severity and mortality of COVID-19-infected HIV patients, even when treated with ART.

HIV infection is associated with an approximately 40% increase in mortality in infected patients with COVID-19 in hospital (15,16). Recent studies show that a low CD4 lymphocyte count in relation to viremia caused by HIV is an important risk factor for the development of serious and fatal COVID-19 (17).  In studies of HIV-infected individuals, COVID-19 mortality is associated with low CD4 lymphocyte counts (18). Therefore, there is a significant association between high HIV RNA and a lower number of CD4 cells (when they are less than 200/mm³), and mortality from COVID-19.  Patients with low CD4 counts due to HIV viremia are at increased risk of severe outcomes and possible death compared to those without HIV infection, with a CD4 count below 200/mm³ increasing the risk of hospitalization (19).

The immunodeficiency that afflicts patients with HIV represents a further risk factor for COVID-19 severity (20). This is true also for individuals who have received an organ transplant and are therefore treated with immunosuppressants (21).

Patients with HIV infection are affected by a chronic inflammatory state, even following treatment with anti-viral drugs (22).  Chronic inflammation can mediate other pathologies such as tumors and cardiovascular diseases. Patients with elevated inflammatory markers have an increased risk of COVID-19 severity, although further studies are still needed to unravel the mechanisms of aetiology and pathogenesis (23).

The COVID-19 pandemic, especially at the beginning of its appearance, created many problems for hospital facilities and healthcare workers, with difficulties in accessing hospital departments, including departments other than infectious disease (24). Some departments were closed, while others stopped their activity. During the COVID-19 pandemic, people with HIV who were previously routinely cared for were suspended in several hospitals with the discontinuation of ART therapy.  Furthermore, it was difficult for patients with HIV to obtain therapeutic prescriptions or reach healthcare facilities. The interruption or temporal delay in treatment against HIV infection has certainly led to an increase in mortality, as anti-HIV therapy must be done promptly and once started, should not be interrupted (25).

The most important tool utilized to combat COVID-19 was the vaccine, which helped significantly to prevent the deterioration and death of HIV patients (26). The anti-COVID-19 vaccination response in HIV patients with normal CD4 T cell counts was satisfactory, and patients developed a good number of anti-SARS-CoV-2 antibodies, results which are similar to those of healthy subjects (27). In HIV patients who had a low CD4 count (less than 250 cells/mm3), there was a low response to vaccination and a low anti-SARS-CoV-2 count (28). However, COVID-19 vaccination is always recommended, even for those with low CD4 cell counts.

Patients with COVID-19 who develop infectious and inflammatory symptoms should receive appropriate therapy. If HIV patients have a low antibody response, they would face increased risks of SARS-CoV-2 infection after vaccination (29). In addition, the risk of contracting the infection is approximately 30% higher in patients with HIV compared to those without HIV. Patients with a CD4 cell count greater than 500/mm3 show a low incidence of infectious damage. The doses of the mRNA vaccine for COVID-19 patients with HIV are not different from those of subjects without HIV. The anti-COVID-19 treatments recommended by the National Institute of Health and Infection Diseases Society of America include Nirmatreivir/Ritonavir, Renedesivivir, and Molnupiravir (30). ART patients are usually treated with Ritonavir and can receive the therapeutic drug Nirmatrelvir-Ritonavir without stopping ART therapy.

Patients with COVID-19 who are hospitalized must be treated with dexamethasone (6 mg/day) and often receive mechanical ventilation in order to reduce lung inflammation and aid breathing, and in addition, they may receive oxygen therapy to lower the risk of death (31). COVID-19 patients infected with HIV should receive the same therapy as patients with COVID-19 alone.

CONCLUSIONS

In conclusion, it can be stated that the COVID-19 pandemic has had a strong impact on patients with HIV infection. COVID-19 patients with HIV infection have been seen to have a higher risk of death than patients with COVID-19 alone, an effect due to the immune deficiency generated by HIV, particularly by acting on CD4 cells. There is a link between HIV infection and the increased severity and mortality of COVID-19 patients, which occurs especially in patients with high HIV viremia and a low number of CD4 lymphocytes.

Conflict of interest

The authors declare that they have no conflict of interest.

REFERENCES

1. Meherali S, Punjani N, Louie-Poon S, et al. Mental Health of Children and Adolescents Amidst COVID-19 and Past Pandemics: A Rapid Systematic Review. International Journal of Environmental Research and Public Health. 2021;18(7):3432. doi:https://doi.org/10.3390/ijerph18073432
2. Arima Y, Kutsuna S, Shimada T, et al. Severe Acute Respiratory Syndrome Coronavirus 2 Infection among Returnees to Japan from Wuhan, China, 2020. Emerging infectious diseases. 2020;26(7):1596-1600. doi:https://doi.org/10.3201/eid2607.200994
3. McElrath MJ, Haynes BF. Induction of Immunity to Human Immunodeficiency Virus Type-1 by Vaccination. Immunity. 2010;33(4):542-554. doi:https://doi.org/10.1016/j.immuni.2010.09.011
4. Parashar S, Collins AB, Montaner JSG, Hogg RS, Milloy MJ. Reducing rates of preventable HIV/AIDS-associated mortality among people living with HIV who inject drugs. Current Opinion in HIV and AIDS. 2016;11(5):507-513. doi:https://doi.org/10.1097/coh.0000000000000297
5. Majumder J, Minko T. Recent Developments on Therapeutic and Diagnostic Approaches for COVID-19. The AAPS Journal. 2021;23(1). doi:https://doi.org/10.1208/s12248-020-00532-2
6. Yüce M, Filiztekin E, Özkaya KG. COVID-19 diagnosis —A review of current methods. Biosensors and Bioelectronics. 2021;172(172):112752. doi:https://doi.org/10.1016/j.bios.2020.112752
7. Ayala G, Arreola S, Howell S, Hoffmann TJ, Santos GM. Enablers and Barriers to HIV Services for Gay and Bisexual Men in the COVID-19 Era: Fusing Data Sets from Two Global Online Surveys Via File Concatenation With Adjusted Weights. JMIR Public Health and Surveillance. 2022;8(6):e33538. doi:https://doi.org/10.2196/33538
8. Patil A, Goldust M, Wollina U. Herpes zoster: A Review of Clinical Manifestations and Management. Viruses. 2022;14(2):192. doi:https://doi.org/10.3390/v14020192
9. Dheda K, Perumal T, Moultrie H, et al. The intersecting pandemics of tuberculosis and COVID-19: population-level and patient-level impact, clinical presentation, and corrective interventions. The Lancet Respiratory Medicine. 2022;10(6). doi:https://doi.org/10.1016/s2213-2600(22)00092-3
10. Jones R, Nelson M, Bracchi M, Asboe D, Boffito M. COVID-19 in patients with HIV. The Lancet HIV. 2020;7(6):e383. doi:https://doi.org/10.1016/s2352-3018(20)30139-9
11. SeyedAlinaghi S, Karimi A, Barzegary A, et al. COVID-19 mortality in patients with immunodeficiency and its predictors: a systematic review. European Journal of Medical Research. 2022;27:195. doi:https://doi.org/10.1186/s40001-022-00824-7
12. Li L, Zhang W, Hu Y, et al. Effect of Convalescent Plasma Therapy on Time to Clinical Improvement in Patients With Severe and Life-threatening COVID-19. JAMA. 2020;324(5):460-470. doi:https://doi.org/10.1001/jama.2020.10044
13. Gesesew HA, Koye DN, Fetene DM, et al. Risk factors for COVID-19 infection, disease severity and related deaths in Africa: a systematic review. BMJ Open. 2021;11(2):e044618. doi:https://doi.org/10.1136/bmjopen-2020-044618
14. Ruterbusch M, Pruner KB, Shehata L, Pepper M. In Vivo CD4+ T Cell Differentiation and Function: Revisiting the Th1/Th2 Paradigm. Annual Review of Immunology. 2020;38(1):705-725. doi:https://doi.org/10.1146/annurev-immunol-103019-085803
15. Feigin VL, Stark BA, Johnson CO, et al. Global, regional, and National Burden of Stroke and Its Risk factors, 1990–2019: a Systematic Analysis for the Global Burden of Disease Study 2019. The Lancet Neurology. 2021;20(10):795-820. doi:https://doi.org/10.1016/s1474-4422(21)00252-0
16. Dzinamarira T, Murewanhema G, Chitungo I, et al. Risk of mortality in HIV-infected COVID-19 patients: A systematic review and meta-analysis. Journal of Infection and Public Health. 2022;15(6):654-661. doi:https://doi.org/10.1016/j.jiph.2022.05.006
17. Guo W, Ming F, Dong Y, et al. Driving force of COVID-19 among people living with HIV in Wuhan, China. AIDS Care. 2022;34(11):1364-1371. doi:https://doi.org/10.1080/09540121.2022.2052259
18. Monteiro MA, Prates GS, de Lima Nascimento NA, et al. SARS-CoV-2/COVID-19: Clinical Course Among Subjects HIV-1-Infected in Sao Paulo. Current HIV Research. 2022;20(6):457-462. doi:https://doi.org/10.2174/1570162×20666220624100248
19. Dandachi D, Geiger G, Montgomery MW, et al. Characteristics, Comorbidities, and Outcomes in a Multicenter Registry of Patients With Human Immunodeficiency Virus and Coronavirus Disease 2019. Clinical Infectious Diseases. 2020;73(7):e1964-e1972. doi:https://doi.org/10.1093/cid/ciaa1339
20. Alzate Angel JC, Martínez-Buitrago E, Posada-Vergara MP. COVID-19 and HIV. Colombia Medica. 2020;51(2):e4327. doi:https://doi.org/10.25100/cm.v51i2.4327
21. Jakharia N, Subramanian A, Shapiro AE. COVID-19 in the Immunocompromised Host, including People with HIV. Infectious Disease Clinics of North America. 2022;36(2):397-421. doi:https://doi.org/10.1016/j.idc.2022.01.006
22. Deeks SG, Lewin SR, Havlir DV. The end of AIDS: HIV infection as a chronic disease. The Lancet. 2013;382(9903):1525-1533. doi:https://doi.org/10.1016/s0140-6736(13)61809-7
23. Yang Y, Iwasaki A. Impact of Chronic HIV Infection on SARS-CoV-2 Infection, COVID-19 Disease and Vaccines. Current HIV/AIDS Reports. 2021;19(1):5-16. doi:https://doi.org/10.1007/s11904-021-00590-x
24. Pormasoumi H, Rostami D, Jamebozorgi K, Mirshekarpour H, Heshmatnia J. COVID-19 management in Iran and international sanctions. European Journal of Translational Myology. 2022;32(4):10777. doi:https://doi.org/10.4081/ejtm.2022.10777
25. Gils T, Bossard C, Verdonck K, et al. Stockouts of HIV commodities in public health facilities in Kinshasa: Barriers to end HIV. Bochenek T, ed. PLOS ONE. 2018;13(1):e0191294. doi:https://doi.org/10.1371/journal.pone.0191294
26. Hanif F, Satiti S, Subagya S, et al. Progressive Worsening of Neurological Manifestations in HIV-Associated Opportunistic Central Nervous System (CNS) Infection Patients After COVID-19 Vaccinations: A Possible Co-Incidence Causality. American Journal of Case Reports. 2022;23. doi:https://doi.org/10.12659/ajcr.936257
27. Tauzin A, Gong SY, Beaudoin-Bussières G, et al. Strong humoral immune responses against SARS-CoV-2 Spike after BNT162b2 mRNA vaccination with a 16-week interval between doses. Cell Host & Microbe. 2022;30(1):97-109.e5. doi:https://doi.org/10.1016/j.chom.2021.12.004
28. Wu S, Zou S, Ming F, et al. Humoral immune response to inactivated COVID-19 vaccination at the 3rd month among people living with HIV. BMC Infectious Diseases. 2023;23(1). doi:https://doi.org/10.1186/s12879-023-07982-x
29. Lee ARYB, Wong SY, Chai LYA, et al. Efficacy of covid-19 vaccines in immunocompromised patients: systematic review and meta-analysis. BMJ. 2022;376:e068632. doi:https://doi.org/10.1136/bmj-2021-068632
30. Mohapatra S, Ananda P, Tripathy S. Pharmacological consideration of COVID-19 infection and vaccines in pregnancy. Journal of the Chinese Medical Association. 2022;85(5):537-542. doi:https://doi.org/10.1097/jcma.0000000000000712
31. Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, Prescott HC. Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review. JAMA. 2020;324(8):782-793. doi:https://doi.org/10.1001/jama.2020.12839