Comorbidities: HIV infection

HIV infection

HIV infection is of particular interest in the current crisis. First, many patients take antiretroviral therapies that are thought to have some effect against SARS-CoV-2. Second, HIV serves as a model of cellular immune deficiency. Third, and by far the most important point, the collateral damage caused by COVID-19 in the HIV population may be much higher than that of COVID-19 itself.

Preliminary data suggest no elevated incidence of COVID-19. In 5,700 patients from New York, only 43 (0.8%) were found to be HIV-positive (Richardson 2020). In Barcelona, the standardized incidence rate was lower in persons living with HIV (PLWH) than in the general population (Inciarte 2020). Given the fact that HIV+ patients may be at higher risk for other infectious diseases such as STDs, these percentages were so low that some experts have already speculated on potential “protective” factors (i.e., antiviral therapies or immune activation). Moreover, a defective cellular immunity could paradoxically be protective for severe cytokine dysregulation, preventing the cytokine storm seen in severe COVID-19 cases.


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Appropriately powered and designed studies that are needed to draw conclusions on the effect of COVID-19 are still lacking. However, our own retrospective analysis of 33 confirmed SARS-CoV-2 infections between March 11 and April 17 in 12 participating German HIV centers revealed no excess morbidity or mortality (Haerter 2020). The clinical case definition was mild in 25/33 cases (76%), severe in 2/33 cases (6%), and critical in 6/33 cases (18%). At the last follow up, 29/32 of patients with documented outcome (90%) had recovered. Three out of 32 patients had died. One patient was 82 years old, one had a CD4 T cell count of 69/µl and one suffered from several comorbidities. A similar observation was made in Milan, Italy, where 45/47 patients with HIV and COVID-19 (only 28 with confirmed SARS-CoV-2 infection) recovered (Gervasoni 2020). In another single center study from Madrid on 51 HIV patients with COVID-19 (35 confirmed cases), six patients were critically ill and two died (Vizcarra 2020). In these studies, as in our cohort, severe immune deficiency was rare. During recent months, there has been growing evidence that HIV+ patients with uncontrolled viremia and/or low CD4 cells are at higher risk for severe disease. In a large population study from South Africa, HIV was independently associated with increased COVID-19 mortality, showing an adjusted hazard ratio for mortality of 2.14 for HIV (95% CI 1.70-2.70) (Boulle 2020). Among 286 HIV-infected patients who were included by US healthcare providers, mortality rates were higher in patients with low CD4 counts (< 200 cells/mm³) (Dandachi 2020).

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There is still an ongoing debate about potential effects of antiretroviral therapies against SARS-CoV-2. For lopinavir/r (and darunavir/r), there is now strong evidence that they don’t work (see Treatment chapter, page 329). An ART regimen should not be changed to include a PI to prevent or treat COVID-19 (EACS 2020, US 2020). Tenofovir alafenamide (TAF) has some chemical similarities to remdesivir and has been shown to bind to SARS-CoV-2 RNA polymerase (RdRp) with high binding energies, and has been suggested as a potential treatment for COVID-19 (Elfiky 2020). In Spain, a large randomized Phase III placebo-controlled study (EPICOS, NCT04334928) compares the use of tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC), hydroxychloroquine or the combination of both versus placebo as prophylaxis for COVID-19 in healthcare workers. Our observation that the majority (22/33) of HIV+ patients with COVID-19 were treated with tenofovir, including those developing severe or critical disease, indicate no or only minimal clinical effect against SARS-CoV-2 (Härter 2020). In the cohorts from Milan and Madrid, there was no evidence that any specific antiretroviral drug (such as tenofovir or PIs) affected COVID-19 susceptibility or severity (Gervasoni 2020, Vizcarra 2020). Most patients, however, have received TAF and not TDF for which preliminary data from Spain suggest a beneficial effect. Of 77,590 HIV+ persons receiving ART in Spain, 236 were diagnosed with COVID-19, 151 were hospitalized, 15 were admitted to the ICU, and 20 died (Del Amo 2020). The risk for COVID-19 hospitalization was higher among patients receiving TAF/FTC and ABC/3TC, compared to those receiving TDF/FTC. However, residual confounding by co-morbid conditions cannot be completely excluded. In a small group from France, attack rates were not lower with TDF/FTC in PrEP users (Charre 2020).


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The most serious concern regarding HIV, however, is the collateral damage induced by COVID-19. In Western countries, there exist few reports of HIV+ patients having problems in gaining access to their HIV medications or having trouble taking them due to COVID-19 or the plans to manage it (Sanchez 2020). In contrast, disruption to delivery of health care in sub-Saharan African settings could well lead to adverse consequences beyond those from COVID-19 itself. Lockdown, transport restrictions and fear of coronavirus infection have already led to a dramatic drop in HIV and TB patients collecting medication in several African countries (Adepoju 2020). Using five different existing mathematical models of HIV epidemiology and intervention programmes in sub-Saharan Africa, investigations have already estimated the impact of different disruptions to HIV prevention and treatment services. Predicted average relative excess in HIV-related deaths and new HIV infections (caused by unsuppressed HIV RNA during treatment interruptions) per year over 2020-2024 in countries in sub-Saharan Africa that would result from 3 months of disruption of HIV-specific services, were 1.20-1.27 for death and 1.02-1.33 for new infections, respectively. A 6-month interruption of ART would result in over 500,000 excess HIV deaths in sub-Saharan Africa (range of estimates 471,000 – 673,000). Disrupted services could also reverse gains made in preventing mother-to-child transmission. According to WHO, there is a clear need for urgent efforts to ensure HIV service continuity and preventing treatment interruptions due to COVID-19 restrictions in sub-Saharan Africa.

References

Adepoju P. Tuberculosis and HIV responses threatened by COVID-19. Lancet HIV. 2020 May;7(5):e319-e320. PubMed: https://pubmed.gov/32277870. Full-text: https://doi.org/10.1016/S2352-3018(20)30109-0

Boulle A, Davies MA, Hussey H, et al. Risk factors for COVID-19 death in a population cohort study from the Western Cape Province, South Africa. Clin Infect Dis. 2020 Aug 29:ciaa1198. PubMed: https://pubmed.gov/32860699. Full-text: https://doi.org/10.1093/cid/ciaa1198

Charre C, Icard V, Pradat P, et al. Coronavirus disease 2019 attack rate in HIV-infected patients and in preexposure prophylaxis users. AIDS. 2020 Oct 1;34(12):1765-1770. PubMed: https://pubmed.gov/32889852. Full-text: https://doi.org/10.1097/QAD.0000000000002639

Dandachi D, Geiger G, Montgomery MW, et al. Characteristics, Comorbidities, and Outcomes in a Multicenter Registry of Patients with HIV and Coronavirus Disease-19. Clin Inf Dis 2020 Sep 9. Full-text: https://doi.org/10.1093/cid/ciaa1339

Del Amo J, Polo R, Moreno S, et al. Incidence and Severity of COVID-19 in HIV-Positive Persons Receiving Antiretroviral Therapy – A Cohort Study. Annals Int Med 2020, June 26. Full-text: https://doi.org/10.7326/M20-3689

EACS & BHIVA. Statement on risk of COVID-19 for people living with HIV (PLWH). https://www.eacsociety.org/home/covid-19-and-hiv.html

Elfiky AA. Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir against SARS-CoV-2 RNA dependent RNA polymerase (RdRp): A molecular docking study. Life Sci. 2020 Mar 25;253:117592. PubMed: https://pubmed.gov/32222463. Full-text: https://doi.org/10.1016/j.lfs.2020.117592

Gervasoni C, Meraviglia P, Riva A, et al. Clinical features and outcomes of HIV patients with coronavirus disease 2019. Clin Infect Dis. 2020 May 14:ciaa579. PubMed: https://pubmed.gov/32407467. Full-text: https://doi.org/10.1093/cid/ciaa579

Härter G, Spinner CD, Roider J, at al. COVID-19 in people living with human immunodeficiency virus: a case series of 33 patients. Infection 2020, May 11. https://doi.org/10.1007/s15010-020-01438-z. Full-text: https://link.springer.com/article/10.1007/s15010-020-01438-z

Inciarte A, Gonzalez-Cordon A, Rojas J, et al. Clinical characteristics, risk factors, and incidence of symptomatic COVID-19 in adults living with HIV: a single-center, prospective observational study. AIDS. 2020 Aug 7. PubMed: https://pubmed.gov/32773471. Full-text: https://doi.org/10.1097/QAD.0000000000002643

Jewell B, Mudimu E, Stover J, et al. Potential effects of disruption to HIV programmes in sub-Saharan Africa caused by COVID-19: results from multiple models. Pre-print, https://doi.org/10.6084/m9.figshare.12279914.v1 + https://doi.org/10.6084/m9.figshare.12279932.v1

Richardson S, Hirsch JS, Narasimhan M, et al. Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. JAMA. 2020 Apr 22:e206775. PubMed: https://pubmed.gov/32320003. Full-text: https://doi.org/10.1001/jama.2020.6775

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 Apr 29:1-9. PubMed: https://pubmed.gov/32350773. Full-text: https://doi.org/10.1007/s10461-020-02894-2

U.S. Department of Health and Human Services. Interim Guidance for COVID-19 and Persons with HIV. https://aidsinfo.nih.gov/guidelines/html/8/covid-19-and-persons-with-hiv–interim-guidance-/554/interim-guidance-for-covid-19-and-persons-with-hiv

Vizcarra P, Pérez-Elías MJ, Quereda C, et al. Description of COVID-19 in HIV-infected individuals: a single-centre, prospective cohort. Lancet HIV. 2020 May 28:S2352-3018(20)30164-8. PubMed: https://pubmed.gov/32473657. Full-text: https://doi.org/10.1016/S2352-3018(20)30164-8