A case report of a man living with HIV in China who appeared to have antibodies for SARS-CoV-2 (the virus that causes COVID-19) but tested negative for the disease and an in vitro study of an antiviral drug seemed to offer some hope in the search for biomedical solutions to the current coronavirus pandemic, but neither has proven realistic so far, other researchers noted.
Delayed SARS-CoV-2 Antibody Response in a Person Living With HIV: Case Report
Chinese researchers reported in Clinical Infectious Diseases on a 38-year-old man who is living with HIV, exhibited COVID-19 symptoms, tested negative for that virus, but eventually had SARS-CoV-2 antibodies in plasma. He was taking lamivudine, tenofovir, and efavirenz (Symfi Lo) for his HIV and had been successfully treated for hepatitis C with direct-acting antivirals. Study authors theorized that some antiretrovirals (ARVs) and/or the interferon activated by HIV itself may help to suppress SARS-CoV-2. The delayed antibody response could be due to initially incomplete clearance of the respiratory virus, they speculated.
The person had traveled to Wuhan, China, and in January presented with fever and right lower pneumonia at a hospital in Shenzen, China. His swabs were tested for SARS-CoV-2, but results were negative. He was admitted to the hospital, treated for the pneumonia, and eventually released. Because of his immune status and prior hepatitis C infection, his immune response was re-evaluated in March. Initially, relatively few SARS-CoV-2 antibodies were detected, but a week later, that level had increased significantly.
By day 49 after the onset of illness, his plasma tested negative for both HIV and hepatitis C—i.e., he had an undetectable HIV viral load and showed a sustained immune response to the earlier hepatitis C treatment—but included a relatively high level of SARS-CoV-2 antibodies. At that time, his partner, who also lives with HIV and takes lopinavir and ritonavir (Kaletra) for that virus, tested negative for the respiratory virus.
Such anecdotal evidence has caused some people living with HIV to wonder whether their ARVs may protect them against SARS-CoV-2. At this time, there is no evidence for such an effect, infectious-disease specialist Paul Sax, M.D., noted in Medscape. Furthermore, a randomized study of lopinavir/ritonavir as a potential treatment for COVID-19 did not show a clinical benefit from the ARV.
This case report is a non-story, Steve Taylor, M.R.C.P., Ph.D., an HIV specialist at Birmingham Heartlands Hospital in the United Kingdom wrote on Twitter. The pneumonia may not have been related to COVID, and it is unclear what the delayed antibody response means for HIV-negative people, he argued. Manik Kohli, Mb.Ch.B., M.S., an HIV researcher from London, suggested in the same Twitter thread that an asymptomatic SARS-CoV-2 infection contracted between the initial pneumonia and when the antibodies were found in plasma may be responsible for the delayed response.
High Dose of Antiparasitic Ivermectin Effective In Vitro Against SARS-CoV-2
Ivermectin, an antiparasitic drug, significantly reduced SARS-CoV-2 viral RNA in vitro, Australian researchers reported in Antiviral Research. The medication had been initially identified as a potential integrase inhibitor against HIV but was later approved by the U.S. Food and Drug Administration (FDA)—not for HIV, but for treatment of roundworm and lice infestations. It is also used for veterinary applications and against river blindness.
The researchers infected cells in the lab with SARS-CoV-2, then applied ivermectin two hours later. Within 48 hours, the viral RNA was reduced about 5,000 fold. The drug acts on the IMPα/β1 heterodimer, which is responsible for nuclear import of integrase protein. However, coronaviruses are not imported into the nucleus, Vincent Racaniello, Ph.D., a virology lecturer at Columbia University who hosts the This Week in Virology podcast series pointed out. Thus, the mechanism of action explored in this study is very different from how the drug works in currently approved applications.
Furthermore, the researchers used a much higher dose of ivermectin than is currently approved for humans, Doris Cully, Ph.D., a pharma consultant who used to work on the drug when it was initially approved by the FDA, noted in the podcast. That dose has never been tested in human safety studies. “The major route of toxicity with ivermectin is the Gaba receptor in the central nervous system,” she explained. We don’t know enough about its effects on the blood-brain barrier if it were given to people who have the SARS-CoV-2 virus, she added. An earlier in vitro study of ivermectin against dengue fever had been promising at doses similar to that used in the current SARS-CoV-2 study, but a Thai phase 3 in vivo study at the lower FDA-approved dose showed no clinical benefit.
Given the ongoing pandemic, all possible drugs should be pursued simultaneously as quickly as possible, the authors of the current study advocated. Benchmark tests of the various treatment options against each other should then be performed at the earliest opportunity. If an effective antiviral against SARS-CoV-2 can be found, it could not only prevent severe disease progression in those with the virus, but also transmission to other people, they noted. The next step is to evaluate a multi-dose regimen, study authors explained.
While ARVs or ivermectin may or may not help against SARS-CoV-2, we do need to explore all possible avenues for beating the pandemic. Even unsuccessful studies help to drive that process forward, by increasing human knowledge and eliminating options for a greater focus on more promising alternatives.