HIV infection

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primary care network: a cross-sectional study. Lancet Infect Dis. 2020 Sep;20(9):10341042. PubMed: https://pubmed.gov/32422204. Full-text: https://doi.org/10.1016/S14733099(20)30371-6 Lippi G, Henry BM. Active smoking is not associated with severity of coronavirus disease 2019 (COVID-19). Eur J Intern Med. 2020 Mar 16. PubMed: https://pubmed.gov/32192856.

Full-text: https://doi.org/10.1016/j.ejim.2020.03.014 Smith JC, Sausville EL, Girish V, et al. Cigarette Smoke Exposure and Inflammatory Signaling

Increase the Expression of the SARS-CoV-2 Receptor ACE2 in the Respiratory Tract.

Dev Cell. 2020 Jun 8;53(5):514-529.e3. PubMed: https://pubmed.gov/32425701. Full-text: https://doi.org/10.1016/j.devcel.2020.05.012

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 5700 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. Appropriately powered and designed studies are still needed to draw conclusions on the effect of COVID-19. In our own retrospective analysis of 33 confirmed SARS-CoV-2 infections between March 11 and April 17 in 12 participating German HIV centers, no excess morbidity or mortality was revealed (Haerter 2020). However, a multicenter cohort study which evaluated risk factors for morbidity and mortality of COVID‐19 in PLWH infected with SARS‐CoV‐2 in three countries, patients with severe COVID‐19 had a lower current CD4 T cell count and a lower CD4 T cell nadir, compared with patients with mild‐to‐moderate COVID‐19 (Hoffmann 2020). In a multivariate analysis, the only factor associated with risk for severe COVID‐19 was a current CD4+ T cell count of < 350/µl (adjusted odds ratio 2,85, 95% CI: 1,26‐6,44, p = 0,01). The only factor associ-ated with mortality was a low CD4 T cell nadir. In a large population study from South Africa, HIV was independently associated with increased COVID-19 mortality,

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showing an adjusted hazard ratio for mortality of 2,14 for HIV (95% CI: 1,702,70) (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). In a large study from the UK (Bhaskaran 2020), PLWH had higher risk of COVID-19 death than those without HIV after adjusting for age and sex: hazard ratio (HR) 2,90 (95% CI: 1,96–4,30; p < 0,0001). 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 385). An ART regimen should not be changed to include a PI to prevent or treat COVID19 (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. In combined cohorts from Milan, Madrid and Germany, there was no evidence that any specific antiretroviral drug (such as tenofovir or PIs) affected COVID-19 susceptibility or severity (Hoffmann 2020). Most patients, however, 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). 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 pro-

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grams 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 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 registra-

tions within the OpenSAFELY platform. Lancet HIV 2020, published 11 December. Fulltext: https://doi.org/10.1016/S2352-3018(20)30305-2 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, Co-morbidities, and Outcomes in a Multicenter Registry of Patients with HIV and Coronavirus Disease-19. Clin Infect

Dis. 2020 Sep 9:ciaa1339. PubMed: https://pubmed.gov/32905581. 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. Ann Intern Med. 2020 Oct 6;173(7):536-541. PubMed: https://pubmed.gov/32589451. 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 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 Oct;48(5):681-686. PubMed: https://pubmed.gov/32394344. Full-text: https://doi.org/10.1007/s15010-020-01438-z