We can now see a light at the end of the COVID-19 tunnel, thanks to a growing amount of positive news on vaccines in development.
There are many COVID-19 vaccines in the pipeline, and most—including the three that are currently the farthest along in development (one by Moderna, one by PFizer/BioNTech, and one by AstraZeneca/Oxford)—do not present any concern when it comes to potential HIV risk.
But a small number of other COVID-19 vaccine candidates have a mechanism of action that could lead to heightened HIV susceptibility within the population of people who receive it, according to a Lancet op-ed published in October.
That op-ed led to a brief flurry of media coverage, but little in the way of solid answers. So we asked several experts: What are these potentially worrisome COVID-19 vaccines, how risky are they, and what is the likelihood that they will be widely used?
What Type of COVID-19 Vaccine Are Scientists Worried Might Increase HIV Risk?
There are four types of COVID-19 vaccines, with multiple candidates of each type in development. All of them attempt to coax the body into generating its own immune response to SARS-CoV-2 infection, but they do so differently:
- Genetic vaccines deliver the coronavirus’s genes into human cells.
- Protein-based vaccines contain coronavirus proteins, but no genetic material.
- Inactivated or attenuated vaccines are created from weakened or killed coronaviruses.
- Viral vector vaccines are genetically re-engineered viruses that have been repurposed to fight disease instead of cause it. Some vectors are designed to enter cells and cause them to make viral proteins; other vectors replicate and carry coronavirus proteins on their surface.
It’s that fourth type of vaccine—the viral vector vaccine —that has been identified as a possible danger. Specifically: vaccines using a vector known as adenovirus type 5, or Ad5.
Why Are Ad5-Vectored COVID-19 Vaccines Considered a Potential HIV Risk?
Because we’ve tried making an HIV vaccine that way in the past, and it didn’t work out well.
The scientists who wrote that recent op-ed in the Lancet were involved, more than a decade ago, in a pair of studies on the efficacy of an experimental HIV-1 vaccine that used an Ad5 vector.
Both trials were halted early because they failed to show any decrease in rates of HIV acquisition. In fact, among men in particular, HIV acquisition risk appeared to increase after receiving the vaccine.
Susan Buchbinder, M.D., a clinical professor at University of California-San Francisco, was one of the leaders of these HIV vaccine studies. She noted in an email interview that it could not be determined exactly why the Ad5-vectored vaccine left some populations more at risk of acquiring HIV.
How Much Additional HIV Risk Could an Ad5 COVID-19 Vaccine Cause?
There’s no way to put a percentage on it, Buchbinder said; The two failed HIV vaccine trials were stopped without analyzing all the factors leading to the study subjects’ seroconversion.
But she pointed to the many non-Ad5 COVID-19 vaccines that are in the works and said that, even though the extent of the potential HIV risk associated with Ad5 vaccines is not known, other types of COVID-19 vaccines should be prioritized.
“If we had no other options, Ad5 might be a more important vector,” agreed Mitchell Warren, the executive director of AVAC, a global HIV prevention advocacy organization. “The bar for Ad5 is higher, and [researchers] must monitor for potential risk.”
What Ad5-Vectored COVID-19 Vaccines Are in the Pipeline?
As of December 2020, four companies have ongoing trials of vaccines using Ad5:
- The Chinese company CanSino Biologics, which is running Phase 3 trials in Russia, Pakistan, Saudi Arabia, and other countries. In June the Chinese military approved the vaccine for soldiers.
- Gamaleya Research Institute, part of Russia’s Ministry of Health, has been running trials of a vaccine called Gam-Covid-Vac Sputnik V, and uses a combination of Ad5 and Ad26, and is being tested in Russia, Belarus, Venezuela, the UAE, and India.
- A San Francisco company Vaxart is working on an oral vaccine for Covid-19 containing Ad5 and last month began giving the pill to volunteers in a Phase 1 clinical trial.
- The California-based ImmunityBio launched a Phase 1 trial of a Covid-19 vaccine using Ad5 in October.
Do People Participating in Ad5 COVID Vaccine Trials Know About This Hypothetical HIV Risk?
Possibly not—and that would be a huge problem, Buchbinder said. “These vaccines are being tested in South Africa, where the PrEP [pre-exposure prophylaxis] uptake is low. That’s our concern,” she said. “People need to consent to increased risk.” She added that HIV infection rates should be monitored to ensure there is no increase in HIV infections in the vaccine arms.
TheBodyPro reached out all four companies studying vaccines with Ad5-vectored vaccines to find out if they had notified any of their trial subjects about the possible HIV risk associated with their vaccines. None responded to requests for comment.
What Are the Chances of Approval for a COVID-19 Vaccine Using the Ad5 Vector?
Approval depends on several things. Most importantly, the vaccine would need to work safely—and stringent regulators, including those in Australia, the European Union, Japan, and the U.S. set a high bar for proof of safety and effectiveness.
It’s unlikely these Ad5 vector COVID-19 vaccines would be used in the U.S., due to the Food and Drug Administration’s strict standards, according to John Moore, Ph.D., a professor of microbiology and immunology at Weill Cornell Medical College. “But in the rest of the world, they might be,” he said. For instance, he added, China and Russia may offer their vaccines widely by giving them away or selling them at cost to resource-poor nations that also have high rates of HIV.
In fact, Russia has taken precisely this approach with its Ad5 vector vaccine, Sputnik V: Even before any study results were publicly released, Russia announced it had negotiated agreements to supply the vaccine to several countries, including Argentina, Brazil, India, and Mexico.
That said, even for a resource-poor country with a high rate of HIV that could especially use an inexpensive COVID-19 vaccine, Warren said there are some safeguards in place.
“Zambia, for example, would need the vaccine to be pre-qualified through the WHO [World Health Organization] and then their own regulator could approve it,” Warren said. “But if they want to distribute the vaccine, they would likely go through Gavi [an international public-private partnership aimed at improving access to vaccinations], and would use South Africa to do that. There is a high degree of awareness in South Africa (about Ad5 and the risk of HIV), and they would have a lot of questions.”
Warren added that all vaccines, whether they use an Ad5 vector or not, must have a full safety and efficacy review, as well as a robust regulatory process. “I hope we don’t see manufacturers cutting corners. Right now it’s just a war of press releases, and China and Russia are opaque. The need for trust and transparency is high. Show us the data.”
If any Ad5 vaccines are approved, they would come with an HIV risk caution, Warren said.
Will Ad5 Vectors Work as Well as (or Better Than) Other COVID-19 Vaccines?
That’s still unclear, because very little data has been made available yet.
In November, a press release from the Russian Direct Investment Fund claimed that an interim analysis of the country’s Ad5 vaccine candidate, Sputnik V, showed it had 92% efficacy. However, the review included only 20 total COVID-19 cases in the vaccinated and placebo groups combined—far too few for the claim be convincing, Moore and other experts say.
Beyond that press release, no reliable data on the effectiveness of an Ad5 vector vaccine for COVID-19 have yet been published in peer-reviewed journals or presented at reputable medical conferences.
If an Ad5 Vaccine May Increase HIV Risk, Does That Mean It Would Cause PrEP to Not Work?
No; PrEP will still work to prevent HIV regardless of the COVID-19 vaccine a person receives. “If someone is on PrEP, which is highly active, I would think this would not be an additional risk,” Buchbinder said. “The challenge is in giving the vaccine to people not on PrEP.”
While countries like the U.S. have a relatively high rate of PrEP use compared to elsewhere in the world, countries in sub-Saharan Africa have an especially low PrEP-to-need ratio, for instance.