ASHM COVID-19 Taskforce interim recommendations regarding COVID-19 and adults living with HIV. Prepared by members of the Taskforce’s HIV, Virology, CALD and Migrant Populations and Practice Management Cluster Groups and the Taskforce Chair, April 2020

Document last updated: April 9th 2020

Disclaimer: This ASHM document is designed to provide available, relevant information to clinicians and other healthcare providers to optimise the health and wellbeing of people living with HIV (PLWHIV) during the COVID-19 pandemic. The recommendations provided are the opinions of the authors and are not intended to provide a standard of care, or practice. This document does not reflect a systematic review of the evidence, but will be revised to include relevant future systematic review findings of the National COVID-19 Clinical Evidence Taskforce(1) and other relevant information. 

Optimise the health of older PLWHIV and/or those with comorbidities
In the general community, people over 60 years of age and people with co-morbidities including hypertension, cardiovascular disease, lung disease, cancer, diabetes and chronic liver disease are at greater risk of poorer outcomes with COVID-19 illness(2-6). The Australian Government Department of Health has advised that Aboriginal and Torres Strait Islander people 50 years and older, with one or more chronic medical conditions, may be at greater risk of serious COVID-19 illness. Hence PLWHIV who are older and/or have co-morbidities are also likely to be at greater risk of having poorer outcomes with the COVID-19 illness. 

Measures to optimise these patients’ health should include supporting smoking cessation, optimising diabetic and blood pressure control. We currently recommend not ceasing or switching away from ACE inhibitors or angiotensin receptor blocker medications: there is not enough evidence that these agents increase the risk of worse outcomes of COVID-19 illness(7) and ceasing or switching these agents may cause harm to otherwise stable patients.  Other key measures include encouraging appropriate exercise, maintaining regular appointments via Telehealth or face-to- face if required, streamlining dispensing of scripts and blood slips, supplying supporting documents for financial assistance and actively referring and encouraging patients to attend Telehealth appointments with medical and allied health specialists. Clinicians should encourage patients to consider Advance Care Planning, as discussed in a recent paper on the clinical presentation and management of COVID-19(8).

Streamline the care of well PLWHIV 
For patients who are well and have been stably virologically suppressed for at least 12 months, scheduling fewer regular appointments, ideally via Telehealth, and deferring HIV viral load and CD4+ cell tests and other routine bloods for up to 6-12 months are reasonable measures. Scripts can be posted to patients, or pharmacies. Blood slips can be posted to patients.  This approach will help well PLWHIV adhere to social distancing measures and minimise their contact with people who are acutely unwell. 

Support health maintenance in all PLHIV
•    All HIV positive patients should be offered the influenza vaccine and also the pneumococcal vaccine as indicated, albeit its supply is currently low worldwide
•    All HIV positive patients, including young and well patients should be supported to cease smoking, exercise appropriately, optimise their sleep and adhere to the current National Health and Medical Research Council draft recommendations on alcohol intake(9), or amounts relevant to underlying health conditions. 

Be aware that health and wellbeing issues may worsen, or emerge during the COVID-19 pandemic for PLWHIV
•    Mental health issues may become more common, or more severe during the COVID-19 pandemic
•    Financial insecurity may impede PLWHIV meeting their HIV healthcare needs and may lead to housing insecurity
•    Domestic violence rates have escalated globally since SARS-CoV-2 emerged
Clinicians are encouraged to use regular appointments to routinely evaluate these issues in all PLWHIV and refer to specialists, community nurses, social workers, peer support, community organisations and other appropriate services, as needed. Clinicians should encourage patients to seek help between appointments if these issues arise.

Be aware of current concerns of PLWHIV about the COVID-19 pandemic
•    PLWHIV have concerns that pharmacy dispensing limits and reports of low stores of medication indicate an impending supply shortage of antiretroviral medications. Clinicians should tell patients that pharmaceutical companies have provided assurance that there is and will be adequate ongoing supply of antiretroviral medications
•    Some culturally and linguistically diverse populations (CALD) report concerns regarding the term’ term ‘social distancing’ and prefer the term ‘physical distancing’
•    CALD populations report concerns about being hospitalised with COVID-19 and having reduced opportunities to use appropriate medical translation services. Clinicians should undertake to optimise appropriate translation services at all opportunities
•    Achieving social distancing and self-quarantine may be impossible in in overcrowded houses, prisons, detention centres and in homeless settings. Clinicians should advocate for their PLWHIV patients experiencing these conditions to receive urgent support to optimise their protection against SARS-CoV-2 infection
•    PLWHIV who are prevented from returning to their home countries are concerned about being able to afford antiretroviral treatment in Australia. Clinicians should contact HIV peak organisations and HIV speciality pharmacists to canvass any currents arrangements and plans to support these patients
•    Medicare Ineligible PLWHIV who reside in Australia and who require medical care including hospitalisation as a result of SARS-CoV-2 infection are concerned about incurring high medical costs in some jurisdictions

Role of HIV antiretrovirals in COVID-19 prevention and treatment
There are no data available that demonstrate that HIV antiretroviral medications can prevent infection with SARS-CoV-2.  One study reported no benefit in time to clinical improvement, or hospital discharge in patients hospitalised with severe COVID-19 who received lopinavir and ritonavir plus standard care versus standard care alone(10). Studies utilising HIV medications for the prevention and treatment of COVID-19 are planned.

HIV infection and risk of SARS-CoV-2 infection and severe COVID-19 illness
It is currently unknown whether being infected with HIV is itself associated with a relative increase in the risk of acquiring SARS-CoV-2 infection, or a relative increase in the risk of worse outcomes with COVID-19 illness. 

There have been few published reports of COVID-19 illness in HIV positive people(2, 11) and all patients reported on survived. A recent informal report from Spain suggests that HIV positive people are not more likely to become infected with SARS-CoV-2, or to develop more severe COVID-19 illness and indeed may have a lower risk than the general population(12). However one must be cautious in interpreting this report until detailed published findings from countries and cities with a high prevalence of PLWHIV are available.

Some immunosuppressed PLWHIV may be at higher risk of SARS-CoV-2 infection and severe COVID-19 illness
Some PLWHIV have a greater level of HIV-related immunosuppression than others and may be more vulnerable to COVID-19 illness. T cell responses are important for the control of the SARS-CoV-1 and MERS-CoV infections(13). In SARS-CoV-2 infection, both antibody and T cell responses have been shown to be involved in the immune response to the virus(14). 

Some people living with HIV may have relatively poor T cell and B cell immune responses and therefore may have poorer outcomes with SARS-CoV-2 infection. Broadly these are people with current immune dysregulation as a result of not being on effective antiretroviral therapy and people with prior severe immunosuppression who have not been able to fully reconstitute their immune system, despite effective antiretroviral therapy(15, 16) and remain vulnerable to respiratory infections(17).

We currently suggest that the following HIV positive patients may be more vulnerable to poorer outcomes with COVID-19 illness because of immunosuppression
•    Those who are not using antiretroviral therapy, or use it intermittently 
•    Those with a current AIDS illness
•    Those patients who have not reconstituted their CD4+ cell count above 350 cells/µL with virologically suppressive antiretroviral therapy 
•    Those whose nadir CD4+ T cell count was <200/µL 

COVID-19 illness, pregnancy and HIV
Early reports on pregnant women with COVID-19 illnesses reveal no maternal deaths, and report that the clinical features and outcomes of COVID-19 illness are not different from non-pregnant women with COVID-19 illness(18-20). Existing evidence suggests people aged under 50 years and females are less likely to have severe outcomes from COVID-19 infection, but more data are awaited to inform the specific situation of pregnant women.  There has been one report of mother-to-child transmission of the SARS-CoV-2 virus and the neonate developed pneumonia, but recovered fully(19). There are no current data on outcomes of HIV positive pregnant women with COVID-19 illness and their newborns. Clinicians are advised to seek specialist advice to optimise health outcomes for HIV positive women seeking to become pregnant, or who are currently pregnant during the COVID-19 pandemic.

Approach to management of PLWHIV with COVID-19 illness
HIV positive people should receive the same supportive treatment for COVID-19 illness as HIV negative people, noting that some PLWHIV will be immunosuppressed, older and have co-morbidities. It has been hypothesised that non-steroidal medications (NSAIDS) may exacerbate COVID-19 illness, (21) although there is limited evidence to support this. Until more data are available, clinicians might consider using paracetamol for management of symptoms of COVID-19 illness, in preference to use of ibuprofen and other NSAIDS. Specialist medical and pharmaceutical advice should be sought for HIV positive patients hospitalised with COVID-19 illness. HIV positive patients should be included in all appropriate COVID-19 clinical treatment trials.

All PLWHIV are strongly encouraged to adhere to measures that reduce infection with SARS-CoV-2
Note that recommended measures to protect against SARS-CoV-2 infection may vary between jurisdictions, but in all jurisdictions the following measures are critical:
•    Social/physical distancing
•    Regular hand washing
•    Refraining from touching the face 
•    Cough etiquette
•    Social quarantine following contact with person with proven or suspected COVID-19 illness

References

1.    National COVID-19 Clinical Evidence Taskforce https://covid19evidence.net.au/.
2.    Wang, D., B. Hu, C. Hu, F. Zhu, X. Liu, J. Zhang, B. Wang, H. Xiang, Z. Cheng, Y. Xiong, Y. Zhao, Y. Li, X. Wang, and Z. Peng. 2020. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA.
3.    Wu, Z., and J. M. McGoogan. 2020. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72314 Cases From the Chinese Center for Disease Control and Prevention. JAMA.
4.    Zhou, F., T. Yu, R. Du, G. Fan, Y. Liu, Z. Liu, J. Xiang, Y. Wang, B. Song, X. Gu, L. Guan, Y. Wei, H. Li, X. Wu, J. Xu, S. Tu, Y. Zhang, H. Chen, and B. Cao. 2020. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 395: 1054-1062.
5.    Severe Outcomes Among Patients with Coronavirus Disease 2019 (COVID-19) United States, February 12–March 16, 2020. MMWR Morb Mortal Wkly Rep. .
6.    Porcheddu, R., C. Serra, D. Kelvin, N. Kelvin, and S. Rubino. 2020. Similarity in Case Fatality Rates (CFR) of COVID-19/SARS-COV-2 in Italy and China. J Infect Dev Ctries 14: 125-128.
7.    Vaduganathan, M., O. Vardeny, T. Michel, J. J. V. McMurray, M. A. Pfeffer, and S. D. Solomon. 2020. Renin-Angiotensin-Aldosterone System Inhibitors in Patients with Covid-19. N Engl J Med.
8.    Thevarajan, I., K. L. Buising, and B. Cowie. 2020. Clinical presentation and management of COVID-19  https://www.mja.com.au/journal/2020/clinical-presentation-and-management-covid-19.
9.    Australian guidelines to reduce health risks from drinking alcohol https://www.nhmrc.gov.au/health-advice/alcohol.
10.    Cao, B., Y. Wang, D. Wen, W. Liu, J. Wang, G. Fan, L. Ruan, B. Song, Y. Cai, M. Wei, X. Li, J. Xia, N. Chen, J. Xiang, T. Yu, T. Bai, X. Xie, L. Zhang, C. Li, Y. Yuan, H. Chen, H. Li, H. Huang, S. Tu, F. Gong, Y. Liu, Y. Wei, C. Dong, F. Zhou, X. Gu, J. Xu, Z. Liu, Y. Zhang, H. Li, L. Shang, K. Wang, K. Li, X. Zhou, X. Dong, Z. Qu, S. Lu, X. Hu, S. Ruan, S. Luo, J. Wu, L. Peng, F. Cheng, L. Pan, J. Zou, C. Jia, J. Wang, X. Liu, S. Wang, X. Wu, Q. Ge, J. He, H. Zhan, F. Qiu, L. Guo, C. Huang, T. Jaki, F. G. Hayden, P. W. Horby, D. Zhang, and C. Wang. 2020. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med.
11.    Zhu, F., Y. Cao, S. Xu, and M. Zhou. 2020. Co-infection of SARS-CoV-2 and HIV in a patient in Wuhan city, China. J Med Virol.
12.    HIV and SARS-CoV-2: What Are the Risks? https://www.clinicaloptions.com/hiv/conference-coverage/retroviruses-2020/european-perspectives/ct5/page-1.
13.    Channappanavar, R., J. Zhao, and S. Perlman. 2014. T cell-mediated immune response to respiratory coronaviruses. Immunol Res 59: 118-128.
14.    Thevarajan, I., T. H. O. Nguyen, M. Koutsakos, J. Druce, L. Caley, C. E. van de Sandt, X. Jia, S. Nicholson, M. Catton, B. Cowie, S. Y. C. Tong, S. R. Lewin, and K. Kedzierska. 2020. Breadth of concomitant immune responses underpinning viral clearance and patient recovery in a non-severe case of COVID-19. In Nature Medicine.
15.    Kelley, C. F., C. M. Kitchen, P. W. Hunt, B. Rodriguez, F. M. Hecht, M. Kitahata, H. M. Crane, J. Willig, M. Mugavero, M. Saag, J. N. Martin, and S. G. Deeks. 2009. Incomplete peripheral CD4+ cell count restoration in HIV-infected patients receiving long-term antiretroviral treatment. Clin Infect Dis 48: 787-794.
16.    Lange, C. G., M. M. Lederman, K. Medvik, R. Asaad, M. Wild, R. Kalayjian, and H. Valdez. 2003. Nadir CD4+ T-cell count and numbers of CD28+ CD4+ T-cells predict functional responses to immunizations in chronic HIV-1 infection. AIDS 17: 2015-2023.
17.    Sogaard, O. S., N. Lohse, J. Gerstoft, G. Kronborg, L. Ostergaard, C. Pedersen, G. Pedersen, H. T. Sorensen, and N. Obel. 2008. Hospitalization for pneumonia among individuals with and without HIV infection, 1995-2007: a Danish population-based, nationwide cohort study. Clin Infect Dis 47: 1345-1353.
18.    Schwartz, D. A. 2020. An Analysis of 38 Pregnant Women with COVID-19, Their Newborn Infants, and Maternal-Fetal Transmission of SARS-CoV-2: Maternal Coronavirus Infections and Pregnancy Outcomes. Arch Pathol Lab Med.
19.    Yu, N., W. Li, Q. Kang, Z. Xiong, S. Wang, X. Lin, Y. Liu, J. Xiao, H. Liu, D. Deng, S. Chen, W. Zeng, L. Feng, and J. Wu. 2020. Clinical features and obstetric and neonatal outcomes of pregnant patients with COVID-19 in Wuhan, China: a retrospective, single-centre, descriptive study. Lancet Infect Dis.
20.    Chen, H., J. Guo, C. Wang, F. Luo, X. Yu, W. Zhang, J. Li, D. Zhao, D. Xu, Q. Gong, J. Liao, H. Yang, W. Hou, and Y. Zhang. 2020. Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. Lancet 395: 809-815.
21.    Day, M. 2020. Covid-19: ibuprofen should not be used for managing symptoms, say doctors and scientists. BMJ 368: m1086.