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Clinical Features, HIV Management, and Outcomes of Patients Coinfected with HIV and SARS-CoV-2

17 Nov 2020 5:29 PM | Anonymous

By: Abbey Jin, PharmD Candidate 2021, St. Louis College of Pharmacy at University of Health Sciences and Pharmacy in St. Louis

Mentor: Alexandria Wilson, Pharm.D., BCPS (AQ-ID); Associate Professor, St. Louis College of Pharmacy at University of Health Sciences and Pharmacy in St. Louis; Clinical Pharmacy Specialist, Infectious Diseases, Washington University Infectious Disease Clinic

Introduction

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has spread rapidly across the world since the first known cases arose out of Wuhan, China in late 2019.1 Coronavirus disease 2019 (COVID-19) was declared a pandemic on March 11th, 2020.2,3 As of the writing of this paper, there have been over 43 million confirmed cases of COVID-19 worldwide, with over 1 million deaths.4 Patients with underlying health conditions may have different outcomes than patients without comorbidities.5,6 In particular, people living with Human Immunodeficiency Virus (PLHIV) have been labelled as a COVID-19 high-risk group due to immunosuppression.7 In a report from Kanwugu et al., published on July 21st 2020, there have been 378 reported cases of COVID-19 among PLHIV worldwide.8 This review will summarize the clinical characteristics, HIV management, and outcomes of PLHIV who are infected with SARS-CoV-2.

Epidemiology of COVID-19 in PLHIV

The first published case of HIV and SARS-CoV-2 coinfection was reported in Wuhan, China in early 2020.8 Mirazaei et al. published a systematic review of 252 cases of HIV and SARS-CoV-2 infections in July 2020.2 The majority of those cases were male (80.9%) with a mean age of 52.7 years on antiretroviral therapy (ART) (98%).2 Many patients also had other chronic health conditions known to increase the risk of COVID-19, such as hypothyroidism, asthma, hyperlipidemia, hypertension, obesity, diabetes, and lung disease. 2,5 Slightly over 20% of the patients in the systematic review were smokers. 2

Clinical Features and Courses of COVID-19 in PLHIV

Upon admission, coinfected patients presented with similar signs and symptoms of COVID-19 to HIV- uninfected patients. Many coinfected patients had upper or lower respiratory infections, fever, cough, headache, dyspnea, malaise, sore throat, arthralgia, gastrointestinal upset, myalgia, lymphopenia, and lung changes, i.e. opacities upon X-ray imaging.2,5,9,10

The following table compares the results of Mirazaei et al.’s systematic review of COVID-19 in PLHIV (percentages calculated from available data) to the largest COVID-19 cohort available as of November 3rd, 2020 (>44,000 patients) and United States (US) COVID-19 case surveillance data of hospitalization and intensive care unit (ICU) admission rates from January 22, 2020 to May 30, 2020. 2,11-13


This data suggests that PLHIV who develop COVID-19 have more severe and critical illnesses, hospitalizations, and ICU admissions than HIV negative patients. A majority (86.9% of 176) of patients had high CD4 counts of at least 200 cells/mm.3 Similarly, a HIV-1 RNA of no more than 1000 copies/mL was seen in a majority (99.1% of 233) of patients with viral load data.2 There have also been some reports of PLHIV presenting with Pneumocystis jirovecii pneumonia and COVID-19.14

Findings from Specific Cohorts

There have been conflicting outcomes concerning the survival rates of PLHIV with COVID-19 compared to the general COVID-19 population. For instance, in the United Kingdom, a cohort of patients from the OpenSAFELY platform reported 14,882 COVID-19 deaths with 25 cases among PLHIV. The study included a total of 17.3 million patients with 27,480 cases among PLHIV who were three times more likely to have a COVID-19-related death compared to HIV negative patients (Hazard Ratio (HR) 2.90, 95% Confidence Interval (CI) 1.96-4.30). The association was even greater in patients of African ethnicity (HR 3.80, 2.15-6.74, vs. HR 1.64, 0.92-2.90, p-interaction=0.045).15 Similarly, in a study from Western Cape, South Africa with a patient repository of 3,460,932, 16% were PLHIV. Of this 16%, 3,978 PLHIV were diagnosed with COVID-19, and 115 PLHIV with COVID-19 died. It was shown that HIV was associated with COVID-19 mortality. The risk was similar across different levels of immunosuppression and viral loads. Standardized mortality ratio for COVID-19-related deaths in PLHIV was 2.39 (95% CI 1.96-2.86).16 Another multicenter cohort study with 286 patients found that PLHIV and COVID-19 with CD4 count below 200 cells/mm3 had a higher risk for death, ICU admission, mechanical ventilation or hospitalization, regardless of viral suppression.17

However, a large scale study of 7,576 patients conducted by the US Veterans Aging Cohort Study, showed no difference in mortality (adjusted HR (aHR) 1.08, 95% CI 0.66-1.75), hospital admission (aHR 1.09, 95% CI 0.85-1.41), intubation (aHR 0.89, 95% CI 0.49-1.59), or ICU admission (aHR 1.08, 95% CI 0.72-1.62) between PLHIV and HIV negative patients with COVID-19. This study matched PLHIV and HIV negative patients to account for potential confounders.18 Another study in New York with a cohort of 100 PLHV and 4,513 HIV negative patients also supported no difference in mortality rates.19 All of these studies were not included in Mirazaei et al.’s systematic review which reported deaths in 14.3% of 252 coinfected patients.2

HIV Management in COVID-19

For PLHIV, the National Institutes of Health (NIH) guidelines for COVID-19 treatment recommend patients continue taking their ART unchanged, including investigational agents, and medications for opportunistic infections (OI) prophylaxis.14

The Guidelines recommend against changing ART regimens to treat or prevent COVID-19.20 However, clinicians are advised to consult with a HIV specialist if the ART needs to be adjusted or if the patient is on a feeding tube. For PLHIV not on ART, it is currently unknown when is best to start taking the ART. Overall, clinical recommendations for management of coinfected patients do not differ from the general population.14

Cohorts that assessed specific ARTs patients were taking at the time of COVID-19 included combination nucleoside reverse transcriptase inhibitors with an integrase inhibitor, nucleos(t)ide reverse transcriptase inhibitors (NRTIs) with protease inhibitors (PIs), or combination therapy with nonnucleoside reverse transcriptase inhibitors (NNRTIs).5,21

There have also been studies of outcomes in coinfected populations on ARTs. A cohort study of 77,590 PLHIV in which 236 were diagnosed with COVID-19, in Spain looked at outcomes of PLHIV receiving tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC), tenofovir alafenamide (TAF)/FTC, abacavir (ABC)/lamivudine (3TC) and other ARTs (3TC in two-drug therapies or NNRTI with PI monotherapy). The results of the study are summarized in the table below. 21


The results of this study suggest a benefit in COVID-19-related outcomes of PLHIV on TDF/FTC compared to other ARTs. The study also suggested ARTs have a protective effect in PLHIV, lessening the risk for serious COVID-19 cases.21 There have been other studies looking at ARTs, like lopinavir/ritonavir and darunavir/cobicistat, for treatment of COVID-19, but have shown no clinical benefit compared to the standard of care or need further investigation, respectively.22,23

Conclusion

Current cases of infection with SARS-CoV-2 in PLHIV present with similar clinical features to HIV uninfected people. Different studies have suggested varied outcomes in PLHIV.15-19 Current COVID-19 treatment guidelines offer the same management recommendations for PLHIV and HIV-patients.14 In PLHIV, there are guidelines for HIV management, which state ARTs should not be changed. In one cohort, the combination of ARTs TDF/FTC showed some benefit compared to other ARTs in COVID-19-related outcomes of PLHIV, but more data is needed.21 Differences in the outcomes observed in the cohorts may be attributed to the retrospective nature of some studies, the differing designs, size of cohort, etc. Due to the novelty of COVID-19, there are still many unanswered questions, including whether CD4 count or viral load in PLHIV are associated with severity of COVID-19, and the impact of different ARTs.2 To make accurate conclusions, there needs to be more data on COVID-19 in PLHIV.

References:

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  2. Mirzaei H, McFarland W, Karamouzian M, Sharifi H. COVID-19 Among People Living with HIV: A Systematic Review [published online ahead of print, 2020 Jul 30]. AIDS Behav. 2020;1-8. doi:10.1007/s10461-020-02983-2.
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  6. Guan WJ, Ni ZY, Hu Y, et al. Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med. 2020;382(18):1708-1720. doi:10.1056/NEJMoa2002032
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  13. Stokes EK, Zambrano LD, Anderson KN, et al. Coronavirus Disease 2019 Case Surveillance — United States, January 22–May 30, 2020. MMWR. 2020 Jun 19;69:759–765. doi:10.15585/mmwr.mm6924e2,
  14. HIV | COVID-19 Treatment Guidelines. COVID-19 Treatment Guidelines. https://www.covid19treatmentguidelines.nih.gov/special-populations/hiv/. Published 2020. Accessed November 6, 2020.
  15. Bhaskaran K, Rentsch CT, MacKenna B, et al. HIV infection and COVID-19 death: population-based cohort analysis of UK primary care data and linked national death registrations within the OpenSAFELY platform. medRxiv. Published online January 1, 2020:2020.08.07.20169490. doi:10.1101/2020.08.07.20169490
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