‘Flying blind’: Doctors race to understand what Covid-19 means for people with HIV

Larry Pike has already survived one pandemic. The 76-year-old Seattle retiree has been living with HIV for 22 years. When Covid-19 hit Seattle, he grew worried. “Just like HIV,” he said, “there’s that ‘Who’s next?’ sort of thing.”

Sure enough, on March 4, the day Amazon asked area workers to stay home, Starbucks announced it would hold a “virtual only” annual shareholders meeting, and Boeing asked its employees not to fly, Pike woke up with a sore throat and a cough. He was alarmed, but then felt better in a day and a half. “I thought, OK, I missed that,” he recalled.

Still, he had a lot of questions. He knew he was at risk of complications from the new virus because of his age, but was unsure if he was also at risk because of his HIV, which can weaken the body’s ability to fight off infections. Like many others living with HIV, he takes antiviral drugs that keep the virus in check and restore the levels of key disease-fighting immune cells.

“When they said, this affects people with compromised immune systems, I thought, what does that mean to us?” said Pike, who is active in numerous AIDS survivor groups.

Doctors who treat people with HIV are asking similar questions, and have launched a study with an existing national network of AIDS research centers to try to get answers quickly.

“When patients ask what is happening with people with HIV and Covid, I’ve had to be honest and say I just don’t know,” said Adrienne Shapiro, an infectious diseases specialist at the University of Washington who treats HIV patients at a clinic in Snohomish County, the site of the nation’s first confirmed case of Covid-19. “We as clinicians have been flying blind in this pandemic.”

Edward “Lalo” Cachay, a professor of medicine at the University of California, San Diego, has been worried as well. Four of

his patients who have HIV have become so sick from Covid-19, they’ve required hospitalization. In his clinic, he faces the same streams of questions as Shapiro. “Patients are asking me, do I need to take off work? If I get it, will I have a more severe form? If my viral load is undetectable, am I good?,” said Cachay. “We just don’t know.”

Both physicians conduct HIV research with CNICS, an NIH-funded network based at the University of Alabama at Birmingham that integrates the medical records of more than 35,000 people whose medical care is closely monitored at eight Centers for AIDS Research around the nation. The network, which has been in place for 15 years, is largely used for studies involving HIV disease management, such as whether certain HIV drugs increase the risk of heart attacks.

Because the network is well-established, with patients enrolled, new studies can be up and running in weeks rather than months or years. “When there is a scientific question, or something comes up in the world — like Covid — we have people and all of their data that we can access quickly,” Shapiro said.

Cachay and Shapiro are leading a team examining the records of people living with HIV who have also had Covid-19. They plan to add coronavirus antibody testing to upcoming patient appointments so they can include in their study people who had asymptomatic or mild cases of the disease without knowing they were sick.

The team, which includes researchers at the Fred Hutchinson Cancer Research Center, UCSD, and UW, are hoping to answer several questions: Are people living with HIV at higher risk of complications if they contract Covid-19? What factors might predict which patients are most at risk? Are people with HIV who contract Covid-19 more likely to be symptomatic? And are people with HIV more likely to die if they do contract the new coronavirus?

So far, those answers have been hard to come by. Very little data about HIV status in Covid patients has emerged from China, where HIV rates are relatively low, Shapiro said. Two new studies from countries hard hit by the virus, Spain and Italy, indicated that patients with HIV fared similarly to those without HIV, but the studies were relatively small. “You put both studies together, it’s only 100 patients, and that’s just not enough,” Shapiro said.

“Using existing data flowing from medical records is probably the sweet spot for finding the answers to these new and pressing questions,” said Michael Pencina, a professor and vice dean for data science at Duke University School of Medicine. Pencina has been cautious about interpreting studies emerging from the early days of the pandemic but says with proper design and sample size, the new HIV study could be robust and clinically useful. “It strikes me as efficient,” he said.

From what he’s seen in his network of HIV survivors, Pike is starting to think that they don’t fare worse than others if they are infected with the coronavirus, unless they have other underlying conditions.

A week after Pike’s short illness in March, he came down with a fever and knew something wasn’t right. A friend he’d spent time with at a fundraiser in late February, Charles Perry, had grown sick enough with Covid-19 to be hospitalized. But Pike couldn’t get tested. His highest temperature was 100.4, just under the 100.5 threshold for testing at that time.

As Pike stayed home wondering if he was infected, the world around him was turning upside down. Schools were closing. Toilet paper was disappearing off shelves. Alaska Airlines was cutting flights. And local Girl Scouts started selling cookies online. “Everything was changing on the outside,” he said.

Pike felt bad, but not terribly so. His fever never got very high, but he was always tired. “I’d sleep 12 hours, wake up and do a little, and then take a nap,” said Pike, who is retired but remains active volunteering, gardening, and walking. “It wasn’t normal for me to be that tired.”

Pike finally got tested for Covid-19 during a routine doctor’s visit, but no one, including himself, thought he actually had the disease. “I didn’t feel I was sick enough to be in any danger,” he said.

The test came back positive.

Pike now thinks that it was likely he was infected when he worked for hours in a small coat-check room with his friend Perry during the fundraiser. A second man working in the room also became ill, Pike said.

While a chest X-ray showed Pike had pneumonia, he never got tremendously ill. That wasn’t the case for Perry, Pike’s close friend and fellow HIV survivor, who was diabetic. Perry, 66, died in the hospital while Pike and other friends were quarantined at home. “You can imagine how that felt for us not being able to visit Charles, and having him die alone,” Pike said.

The question of whether HIV makes people more vulnerable to Covid-19 is complicated by the fact that many people with HIV share risk factors with those who are more likely to die of Covid-19, including systematic racism, poor insurance coverage, food insecurity, and unstable housing. “From the very beginning, I’ve been interested in how health care disparities and psychosocial factors affect HIV outcome in the U.S.,” Cachay said. “The same is true for Covid-19.”

The team also wants to look at the particularities of the immune systems in those with HIV. Shapiro said people with HIV often experience inflammation of the lungs that makes it much more likely for seasonal flu to progress to pneumonia. She’s worried the same may be true for the coronavirus.

The doctors also plan to study whether those with low counts of CD4 immune cells, which are targeted by HIV, do worse when infected by the coronavirus. “With both Covid and HIV, it’s not one size fits all,” Shapiro said. “We’ve got a lot to tease out.”

Cachay is concerned for his patients because HIV causes many to age prematurely. “Fifty in HIV is like 65 in the general population,” he said. And many people living with HIV have comorbidities like heart disease that make them more vulnerable to the coronavirus.

Cachay predicts the team will have preliminary data by early fall and more robust data within a year. The rapid work is only possible, he said, because CNICS involves the collaboration of teams of researchers who cooperate rather than compete to be first. “We need to see more of that in research, and in society in general,” Cachay said.

The ability to move coronavirus research ahead so quickly is a result of the longstanding health activism of people with HIV, said Shapiro. “These fast clinical trials, the rapid access to drugs, the engagement of the FDA, is absolutely the legacy of the AIDS epidemic,” she said. Studies like this one, she said, would not be possible without the many patients with HIV who consented to release their data in an effort to help others.

Pike is among those. While he still gets breathless when he tries to walk the steep streets in his neighborhood near Seattle’s Capitol Hill, he’s regaining his strength and has signed up for a new study of the plasma of coronavirus survivors. “Hopefully having my blood to play with,” he said, “will help answer some questions.”