Despite Gileads Promising HIV Prevention Drug, A Vaccine Is Still The Holy Grail – Forbes

July 28, 2024

Until theres a cure or a vaccine, we will need to sustain the AIDS response beyond 2030, UNAIDS Executive Director Winnie Byanyima said last month.

When drugmaker Gilead Sciences announced interim late-stage trial results of its injectable HIV prevention drug last month, researchers, advocates and Wall Street collectively rejoiced. None of the more than 2,000 women at high risk for contracting HIV who were given two annual injections of lenacapavir were infected. It is gobsmackingly exciting to see zero in a clinical trial, Mitchell Warren, executive director of the global HIV prevention nonprofit AVAC told Forbes.

The results were so promising that an independent committee recommended all of the 5,300 women participating in the trial get the twice-yearly injections rather than continuing with comparison groups taking daily oral pills, which averaged around two out of every 100 women getting infected. As the 25th annual International AIDS Conference kicks off in Munich this week, California-based Gilead is expected to release the full data from the Phase 3 trial; additional data from a trial including men and transgender people is expected by early next year. But the potential of a new long-acting HIV prevention tool could be short-lived as the perennial political football enters the equation: cost.

There's so much trepidation in the HIV community about how it's going to be made accessible, Monica Gandhi, a professor of medicine and director of the UCSF Center for AIDS Research, told Forbes. Who's going to get it? Only rich people in the United States, not anyone in Sub-Saharan Africa.

Lenacapavir is already approved as a twice-yearly antiretroviral treatment for people with multi-drug resistant HIV (which costs $42,250 for the first year of treatment and $39,000 each year after in the U.S.). This most recent trial is focused instead on using it as a prevention tool known as pre-exposure prophylaxis, or PrEP, which is for people at high-risk of contracting the disease. As Gilead waits for more clinical trial data and pursues regulatory clearance, it is too early to state the price of lenacapavir for PrEP, Gilead spokesperson Meaghan Smith told Forbes in an email.

In a press release, Gilead said it plans to ensure supply in countries where the need is greatest, until it negotiates voluntary licensing agreements, which usually allow for some lower income countries to get generic versions of brand name drugs at a fraction of the cost. The concern is that even at a much-lower price point, it would still be out of reach for many people in the most hard-hit regions of the world. Gilead would not say whether it specifically intends to work with the U.N.-backed Medicines Patents Pool on these agreements.

Around 39.9 million people worldwide are living with HIV and there are an estimated 1.3 million new infections each year, with cases rising in the Middle East and North Africa, Eastern Europe, central Asia and Latin America, according to the latest numbers from the Joint United Nations Program on HIV/AIDS, or UNAIDS. In 2016, the U.N. General Assembly adopted a target of ending AIDS by 2030, but this is unlikely. Even UNAIDS acknowledges the world is off track. New HIV infections are three times higher than the 2025 target, funding for HIV prevention is shrinking worldwide, a quarter of people infected arent receiving treatment and regressive policies from authoritarian governments are hindering access to prevention.

While there have been amazing advances with PrEP options, people need to continue taking the medication as long as they remain at-risk, which could be an entire lifetime. The obvious solution would be a much cheaper vaccine that could provide years of protection, but its a research puzzle that has eluded top scientists in government, academia and industry for more than two decades. Until theres a cure or a vaccine, we will need to sustain the AIDS response beyond 2030, in every part of the world, UNAIDS Executive Director Winnie Byanyima said last month.

Governments, nonprofits and companies have spent upwards of $18 billion on HIV vaccine research since 2000, per AVAC estimates; not a single clinical trial has made it beyond Phase 3. In January of last year, Johnson and Johnson pulled the plug on its Mosaico trial after it failed to show an effective response. And in December 2023, PrEPVacc, the final remaining late-stage HIV vaccine trial, was stopped early when it was determined there was little or no chance of an effective response.

AIDS activists demonstrating in Spring 1991 at Grand Central Station in New York City, NY. Today a person dies from AIDS-related causes every minute.

In an untreated person, HIV will generate around 10 billion new virus particles per day. While antiretrovirals have done wonders to prevent and control HIV infection, most people have to stay on them for life, or else the virus will start replicating in their bodies with a vengeance. Its for this very reason that developing a vaccine that would help the body generate its own active immune response to keep the virus in check is the holy grail of HIV prevention, Jim Kublin, executive director of the HIV Vaccine Trials Network based at Fred Hutch Cancer Center told Forbes.

The dream would be to have a vaccine that protects a person for years on end like the ones that exist for tetanus or smallpox or, even better, for a lifetime, like the measles vaccine. Gileads lenacapavir results for the twice-yearly shot only raise the bar for any future vaccines, said Warren of the prevention nonprofit AVAC. The vaccine would have to have a similarly high rate of stopping infections, last much longer in duration and be priced much lower.

There are several big challenges with HIV that boil down to the same principle: its a very sneaky escape artist that is constantly changing and using decoys to evade capture by the immune system. The usual approach for many vaccines is to introduce inactivated virus or pieces of virus into the body so that the immune system can prepare a response in advance of infection. But HIV relies on a series of tricks that makes it incredibly challenging for the body to even recognize it is an invader in the first place, including infecting the very cells that are supposed to trigger the response.

As a point of comparison, take Sars-CoV-2, the virus that caused the coronavirus pandemic, which takes its name from the Latin word for crown. Thats because when it enters the body, its like a brilliant glittering diamond-encrusted tiara, in which each diamond is a spike protein that tells the body it's an invader. HIV, on the other hand, is just a plain metal crown with only a handful of diamonds placed few and far between and some of those are decoys. That makes it not only hard for the body to recognize it as a virus, but it also acts as a form of armor preventing antibodies from latching on.

HIV is also mutating at an extremely high rate, so even if the body does end up spotting the invader, HIV has already come up with another disguise by the time it generates a response. It's constantly evolving, sacrificing what it was before in order to try to evolve to its environment very, very quickly, Katharine Bar, an infectious disease doctor and associate professor at the University of Pennsylvania told Forbes.

Most vaccines on the market for other diseases try to jumpstart the bodys natural immune response. In the case of HIV, the natural [response] fails, Otto Yang, professor and associate chief of infectious diseases at UCLA Health, told Forbes. If you try to copy it, he said, you're copying a failing process. One potential solution is to re-engineer the immune system to generate a response that attacks the rare spots in the virus structure that are less likely to mutate. There's some parts of the viruses that hopefully are like Achilles heels, said Yang.

He likens the current efforts by scientists working on multiple types of vaccine responses to top-secret World War II codebreakers in Englands Bletchley Park. You're trying to solve something that's unknown, and you're getting together the best minds to figure out how to decode the enigma machines, said Yang, though he is not confident that an HIV vaccine is currently possible without a major breakthrough. And theres generally agreement in the research community that any successful vaccine would need to combine multiple methods.

And even if it ever does come to pass, an HIV vaccine wont be a silver bullet. The key, says Gandhi of UCSF, is to give people who are at-risk of HIV infection a choice. Theres so far been low uptake of PrEP in Africa, particularly among high-risk groups like young women, due to a combination of factors, including stigma, lack of awareness and distrust. Some people will be okay with a daily pill, while others might want a shot. It's really a matter of providing these options, just like contraception, Gandhi said.

While the decades-long quest for an HIV vaccine has yet to be successful, what scientists have learned along the way has majorly contributed to how the world has responded to other pandemics, like the rapid development of Covid-19 vaccines. The Nobel Prize-winning research of Katalin Karik and Drew Weissman underpinning the mRNA Covid vaccines from Moderna and Pfizer/BioNTech originated two decades ago in the quest for an HIV vaccine. We learn a ton from trying to do the hardest thing, said Bar.

When will it finally pay off? There's this sort of sad aphorism that we're always 10 years away from an effective HIV vaccine, she said. But I think science doesn't necessarily move at a linear pace. It's a big breakthrough followed by iterative changes, followed by another breakthrough.

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