As COVID-19 rapidly spread, the global HIV community grew increasingly concerned about the potential impact of COVID-19 on the 37.9 million people living with HIV, or PLHIV, globally. Would HIV infection be a risk factor for COVID-19 infection or mortality?
Fortunately, most data suggests that PLHIV who are virally suppressed on antiretroviral therapy, known as ART, and have a strong immune system, as measured by CD4 count, are similar to the general population regarding their risk of acquiring COVID-19 or having severe COVID-19 disease although a recent report from South Africa has suggested a higher risk of death in PLHIV, regardless of ART status.
It is still unclear whether advanced HIV disease, or AHD, diagnosed when someone has a CD4 cell count of <200 cells/µl, is associated with increased risk of COVID-19 infection and mortality when compared to the general population. Studies of hospitalized patients with COVID-19 found that lower lymphocyte counts — including subsets such as CD4 — caused by SARS-CoV-2, the virus that causes COVID-19, were associated with severe disease and increased mortality. However, this does not necessarily equate to increased risk for those with lower CD4 counts prior to COVID-19 infection.
There is overall growing awareness that even if PLHIV are not at increased direct risk from COVID-19 itself, the wide-ranging impact on the health care system associated with the COVID-19 response has the potential to have a detrimental impact on hard-won gains in the HIV response, especially the dramatic decrease in new HIV infections and AIDS-related deaths that have resulted from expansion of HIV testing, treatment, and prevention programs.
Indirect negative impact of COVID-19 on PLHIV
COVID-19 has led to service delivery disruptions across the globe due to a variety of factors, including avoidance of health care facilities because of fear of infection, inability to access clinics due to restrictions on movement and travel, and inability to afford transport or items such as masks needed for facility visits due to income loss. In addition, key services such as HIV testing, prevention activities, and adherence counseling have been curtailed due to social distancing requirements and diversion of resources to COVID-19 control.
These disruptions in services could have serious repercussions for the HIV response, especially in sub-Saharan Africa. A recent report released by the World Health Organization and UNAIDS estimated that up to 500,000 excess deaths from HIV-related illnesses could result from a prolonged interruption of ART.
The main contributor to these excess deaths is the rapid decrease in CD4 cell counts that occurs after ART is stopped. Although it may take years of ART to achieve immune recovery, those gains are lost quickly, with studies showing a median loss of 187 CD4 cells/µl after just 2 months off ART. One-quarter of people will lose >300 cells/µl in that time.
Advanced HIV disease — a critical vulnerability
Patients already diagnosed with AHD are a particularly high-risk group for COVID-related service delivery disruptions for reasons that include the following:
• By definition, AHD patients have a lower CD4, so they have less “buffer” for declines in CD4. Even a small decrease in CD4 related to ART interruption or undetected increase in viral load could result in severe immunosuppression, placing these patients at increased risk for opportunistic infections, wasting syndromes, and other life-threatening conditions.
• In addition to ART, people living with AHD may require medications such as cotrimoxazole and pre-emptive fluconazole therapy; interruptions in supply of these drugs increases risk for new or rebounding infections.
• Decreased access to facilities limits opportunities for patients with AHD to receive critical diagnostic procedures such as cryptococcal antigen screening and TB screening and testing, increasing potential for undetected infections.
• Overlap in the clinical presentation of COVID-19 and diseases associated with AHD (for example, tuberculosis and Pneumocystis pneumonia) can make diagnosis more difficult and lead to poorer outcomes due to misdiagnosis.
COVID-related disruptions may lead to increased numbers of patients with AHD
• Currently, about one-third of all newly diagnosed PLHIV have AHD at presentation, and over 50% of those who are returning to care after an ART interruption have AHD. There is a strong possibility that COVID-related disruptions could make these numbers even higher. A key observation is that HIV testing services have decreased dramatically in most settings, delaying new HIV diagnoses, making it more likely that a patient will develop AHD.
• Opportunities for CD4 testing and identification of PLHIV with AHD have been reduced due to decreased health care facility visits, putting PLHIV at serious risk due to missed diagnostics.
• Viral load monitoring has been adversely affected. Patients are avoiding facility visits, and even in cases where viral load samples have been collected, prolonged turnaround times may occur due to diversions of laboratory resources for COVID testing. These factors increase the risk that patients with treatment failure will go undetected and CD4 declines will result.
• Despite the incredible efforts of HIV programs to ensure continuous ART supply using multimonth dispensing and community-based deliveries, it is inevitable that some patients will experience ART interruption and/or be lost to follow up. Efforts to trace these patients and bring them back to care will be delayed by lockdown and social distancing.
Minimizing the effects of COVID-19 on AHD and HIV-related mortality
Because of the increased vulnerability of people with AHD and the potential for increased numbers of patients with AHD, it is critical that actions are taken to minimize the effects of COVID-19 on HIV-related mortality. The following five key steps can avoid preventable deaths from AHD:
1. Develop clear messages to ensure that PLHIV are aware when they should seek medical services. Although unnecessary trips to health facilities should be avoided, it is critical that all patients with serious symptoms, especially those with AHD, are encouraged to present for care. Community-based organizations and networks can be key partners in spreading accurate information about the serious symptoms that require an evaluation — for example severe headache, fever, persistent cough, shortness of breath — and helping patients get necessary medical attention. To allay fears about exposure to coronavirus at facilities, it is also important to make patients aware of the infection control strategies in place for their protection.
2. Address stigma related to HIV and COVID-19 to ensure that PLHIV disclose their HIV status if they develop any symptoms resembling those of COVID-19 and are tested or treated for the disease.
3. Ensure maintenance of services during lockdown for those vulnerable to AIDS-related illness. In addition to providing a continuous ART and cotrimoxazole supply, it is critical that the key diagnostic components related to AHD — including but not limited to CD4 testing, cryptococcal antigen screening and TB testing — remain available for patients who need them. If possible, patients with AHD should also be targeted for more intensive virtual support to help maintain adherence to ART.
4. Continue to optimize CD4 testing networks so that all PLHIV have access to CD4 testing. CD4 is the critical gateway for identification of PLHIV with AHD, and CD4 testing is recommended prior to ART initiation, after interruption in care, and in PLHIV who are not virally suppressed. With the current service delivery disruptions and anticipated increases in ART interruption and loss to follow up, programs should plan for increased CD4 needs to identify patients with AHD.
5. Continue efforts to roll-out the entire AHD package of care. Despite evidence that the AHD package saves lives, implementation has thus far been suboptimal. Now more than ever, it is time to galvanize communities and public health leaders to make the AHD package a reality.
Decades of investment in HIV programs have resulted in widespread access to quality care for millions of PLHIV. It is critical that we focus on ensuring these health services and diagnostic tests are maintained during the COVID-19 response and, as countries emerge from lockdown, we are ready to welcome PLHIV back to care and can identify those with AHD. Only in this way can we ensure that increased deaths from AHD are not added to the long list of losses resulting from the current pandemic.
Visit the knowyourcount.devex.com series for more coverage on how to make diagnostic tests and treatment for advanced HIV patients more accessible by sharing insights from practitioners, policymakers, and people living with AHD. You can join the conversation using the hashtag #AdvancedHIV.