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An update on HIV infection in the current crisis
HIV infection is of particular interest in the current crisis. First, many patients take antiretroviral therapies that are thought to have some effects against SARS-CoV-2. Second, HIV serves as a model of cellular immune deficiency. Third and by the far most important point, the collateral damage caused by COVID-19 in the HIV population may be much higher than that of COVID-19 itself.
Inexplicably, information on the HIV population is still scarce. However, 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). Similar findings were reported from Chicago (Ridgeway 2020). In Barcelona where a local protocol included HIV serology for all hospitalized COVID-19 patients, 32/2102 (1.5%) were HIV-infected, among them only one single new HIV diagnosis (Miro 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 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 this study, as in our cohort, severe immune deficiency was rare. The last median CD4 count was 670/µl (range, 69 to 1715) and in 30/32 cases in our cohort, the latest HIV RNA was below 50 copies/mL (Härter 2020). It remains to be seen whether HIV patients with uncontrolled viremia and/or low CD4 cells are at higher risk for severe disease. It is also unclear whether immunity after infection remains impaired. However, there are case reports on delayed antibody response in HIV patients (Zhao 2020).
Another issue making HIV patients an interesting population is a potential effect of antiretroviral therapies against SARS-CoV-2. For lopinavir/r, some reports on beneficial effects in patients with SARS, MERS and COVID-19 exist, but the evidence remains poor. Several studies on lopinavir are still underway (see Treatment chapter). According to both the US DHHS and EACS statement, an ART regimen should not be changed to include a PI to prevent or treat COVID-19 (EACS 2020, US 2020). In our cohort, 4/33 (12%) patients were on darunavir when they developed COVID-19 symptoms. In the Milan Cohort, the rate of patients on a PI was 11% (Gervasoni 2020). Both studies indicate that PIs do not protect from SARS-CoV-2 infection. Beside the PI, we did not find any clear evidence for a protective effect of tenofovir. Tenofovir alafenamide has some chemical similarities to remdesivir and has been shown to bind to SARS-CoV-2 RNA polymerase (RdRp) with binding energies comparable to those of native nucleotides and to a similar extent as remdesivir. Consequently, tenofovir has recently 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/emtricitabine, 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 Milan, 42% were receiving a tenofovir-based regimen (Gervasoni 2020).
The most serious concern regarding HIV, however, is the collateral damage induced by COVID-19. In Western countries, only few HIV+ patients had problems in gaining access to their HIV medications or had 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, Jewell 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 specific HIV 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.
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
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
Miró JM, Ambrosioni J, Blanco JL. COVID-19 in patients with HIV – Authors’ reply. Lancet HIV. 2020 May 14:S2352-3018(20)30140-5. PubMed: https://pubmed.gov/32416770. Full-text: https://doi.org/10.1016/S2352-3018(20)30140-5
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
Ridgway JP, Schmitt J, Friedman E, et al. HIV Care Continuum and COVID-19 Outcomes Among People Living with HIV During the COVID-19 Pandemic, Chicago, IL. AIDS Behav. 2020 May 7:1-3. PubMed: https://pubmed.gov/32382823. Full-text: https://doi.org/10.1007/s10461-020-02905-2
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
Zhao J, Liao X, Wang H, et al. Early virus clearance and delayed antibody response in a case of COVID-19 with a history of co-infection with HIV-1 and HCV. Clin Infect Dis. 2020 Apr 9:ciaa408. PubMed: https://pubmed.gov/32270178. Full-text: https://doi.org/10.1093/cid/ciaa408