COVID-19 in HIV: a Review of Published Case Reports

Patients with COVID-19 present with a myriad of comorbidities. An immunocompromised state like HIV in patients with COVID-19 can be life-threatening. We searched PubMed/Medline, Scopus, and Web of Science for case reports and case series about COVID-19 in HIV patients. We finally reviewed 20 case reports including cases of 43 patients with HIV and COVID-19. The mean age of 43 adult patients was 51.56 ± 27.56 years (range 24–76 years). Of these, 30 were male (69.77%), 11 were female (25.58%), and 2 were transgender (4.65%). A total of 25 patients (58.14%) were above 50 years of age. The most common cardiovascular comorbidities were hypertension and hyperlipidemia (48.8%), diabetes (20.93%), and morbid obesity (11.63%). Out of 43 HIV patients with COVID-19, 6 resulted in death (13.95%). All the patients who died were elderly above 50 years and required mechanical ventilation. HIV patients infected with COVID-19 had a high mortality rate. A high burden of pre-existing comorbidities and an advanced age in these patients make them prone to disease progression and worse outcomes.


Introduction
Coronavirus disease , caused by the novel SARS-CoV-2 virus, was declared a global pandemic by the World Health Organization on 11 March 2020. Earlier it has caused diseases like Middle East respiratory syndrome (MERS) in Saudi Arabia in 2012 and severe acute respiratory syndromes (SARS) in China in 2002. The single-stranded RNA genome virus has overwhelmed the healthcare system all across the world. People living with human immunodeficiency virus (HIV), advanced age (> 60 years), hypertension (HTN), and diabetes mellitus (DM) are at an increased risk of mortality and morbidity. HIV (human immunodeficiency virus) pandemic coexisting with another pandemic like COVID-19 is called syndemic. This group of HIV-positive individuals, who are unable to practice socialdistancing, have limited access to healthcare, and are prone to drug abuse, will be severely affected. The antiretroviral therapy (ART) has helped in prolonging the lifespan of HIV-positive patients, but the concurrent occurrence of COVID-19 and HIV is presenting unique challenges to the management of these patients. Difficulty in the timely refill of ART medications, a restricted visit to doctors, increased stressors like loneliness, loss of jobs, and fear of homelessness could culminate in substance abuse, a rise in acquired immunodeficiency syndrome (AIDS)-related diseases, and psychiatric problems [1]. The condition could be worse in areas with the already overburdened healthcare system and diversion of public health resources to combat COVID-19. It can make this vulnerable population face unprecedented challenges to maintain their continuity of care [2]. With no cure at hand, practicing social distancing is playing a major role in minimizing the spread of the coronavirus This article is part of the Topical Collection on  infection but can result in decreased adherence to ART therapy and the health outcomes of these patients will take a downhill course [3]. Therefore, we aim to systematically review all published cases of HIV patients with COVID-19 and related clinical correlates and outcomes.

Methods
We searched PubMed/Medline, Web of Science, and Scopus until 1 August 2020 for case reports and case series using the following keywords: COVID-19, SARS-CoV-2, HIV, and human immunodeficiency virus. All published case reports included in the final analysis were in the English language. Our search identified 167 studies in total. After removing the duplicates and selecting case reports or case series with individual patient-level data, we found 23 articles. Due to a lack of data, we further excluded 3 articles and finally include 20 articles [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]. Continuous variables were presented as means ± standard deviations and categorical data as absolute values and percentages. All data extraction and descriptive analysis were performed using Microsoft Excel.
When looking at the contact history of the 43 patients, 34 patients (79.07%) had no contact history reported. Out of the 9 patients who did have a contact history, 2 denied any sick contacts, 1 had a friend with flu symptoms, 1 had an indirect exposure to a COVID-19-positive patient, 1 of the patients was a pharmacist exposed to COVID-19, another was a sex worker, 1 had dinner 5 days prior with a COVID-19-positive person, another took a trip to Florida, and lastly 1 of the exposed patients was a healthcare worker. There was only one case that reported the meantime from exposure to infection of 12 days. CD4 counts were reported in 32 patients of which, 17 (53.13%) had a CD4 count lower than the normal range (< 500 cells/mm 3 ). Nine (20.93%) of the patients had undetectable HIV-RNA (copies/ml) or viral load. Of 30 cases reporting SPO 2 data, 13 (45.1%) had oxygen saturation less than 95% at the time of admission.
Out of 43 HIV patients with COVID-19, 6 (13.95%) patients died during hospitalization, while the remaining 37 (86.05%) recovered ( Table 2). The mean age of the patients that resulted in death was 63.5 ± 12.5 (range 52-76). Of the 6 that died, 5 had bilateral ground-glass opacities on computed tomography scan/chest x-ray, had low oxygen saturation, required mechanical ventilation, and their hospitalization ranged from 1 to 14 days. Of the 37 recovered, 8 patients were on hydroxychloroquine (HCQ) and 1 patient was on chloroquine (CQ). All the patients were on different antiretroviral therapy regimens.

Discussion
The key findings of the current review suggest that HIV patients with COVID-19 infection have a high burden of cardiovascular comorbidities. Furthermore, most of the patients were elderly and male. The most common presenting symptoms were fever, cough, and shortness of breath as reported in COVID-19 patients. Besides, the majority of HIV patients with COVID-19 infection were on ART therapy. The patients who did not recover were mostly elderly (> 50 years) and had cardiovascular comorbidities including HTN, DM, or both. A study by Shahid et al. stated that the older COVID-19 patients with comorbidities such as DM have an increased risk of mortality [24]. Of 6 patients who died, 5 received HCQ with some having a combination of HCQ and/or azithromycin (AZM) and/or 3rd-generation cephalosporins. Of the 37 recovered patients, 11 were on ritonavir (RTV), and 8 of which were on lopinavir (LPV) as well. A study by Yu and colleagues found that influenza-coinfected patients taking lopinavir/ritonavir(LPV/r) treatment had faster pneumonia recovery than those who did not [25]. A therapeutic protective role of anti-HIV agents against COVID-19 infections has been reported [15]. Besides this, high mortality (13.95%) was reported in these patients. Of those that recovered, 17 (39.53%) were reported to be taking a combination of tenofovir (TDF) and emtricitabine (FTC) and 3 (6.98%) patients were taking TDF with other combinations of drugs. A study by Amo et al. suggested that HIV-positive patients on treatment with TDF and FTC proved to have a lower risk of COVID-19-related hospitalization [26]. Only 1 out of the 6 patients that did not recover was receiving tenofovir (TDF) and emtricitabine (FTC) as a combination. ART therapy seems to play a crucial role in protecting HIV patients from COVID-19-related hospitalization. However, key challenges have been reported by this high-risk population in timely accessing preand post-exposure prophylaxis during this pandemic [27]. Policymakers in different countries have proposed and implemented a support framework at a different level to support HIV patients during the COVID-19 pandemic [27,28].

Limitations
Limitations associated with this article should be taken into due consideration while drawing any inference. This review only included the case reports or case series with individual patient-level data so the finding could not be generalized. Furthermore, owing to the small sample size, it is not possible to compare the findings between the deceased and survived groups. Besides, data on CD4 count and viral load were missing in a lot of patients which would make it difficult for any subgroup comparison.

Conclusion
In our review, we found that HIV patients with COVID-19 had a high burden of HTN and/or DM and were over the age of 50. The patients who recovered were on a combination of specific ART therapy which was backed up by research in having a protective role against COVID-19 which could have played a role in their recovery. This review gives a glimpse to look deeper into other treatment options such as anti-viral agents like TDF and LPV/r given that the patients over the age of 50 years with HTN and/or DM that did end up recovering were on one or another of these medications.

Compliance with Ethical Standards
Conflict of Interest The authors declare that they have no conflict of interest.
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