Eradicating HIV Remains Just Out of Reach

The landscape of HIV/AIDS therapy looks vastly different today than it did during the height of the epidemic 3 decades ago. For millions of people around the world, HIV is a chronic condition, not a death sentence.

And yet, insofar as the goal of HIV research is eradication, the scientific community remains in a frustrating position: close enough to see the finish line, but with no idea how far away it is.

There’s no vaccine to prevent infection with HIV. And there’s no cure for people who have it. But the vast majority of people who take pre-exposure prophylaxis (PrEP) drug Truvada are functionally safe from infection. And the vast majority of people who have HIV are able to find an antiretroviral therapy (ART) that successfully suppresses their viral load, provided they can get access to the drug. The US Centers for Disease Control and Prevention (CDC) now says that if a patient’s viral load has been suppressed to the point of undetectability, then the patient cannot transmit HIV.

And so, the HIV research and advocacy community finds itself in the middle of a major paradox. On the one hand, we now have the technology to “functionally” cure patients with HIV. On the other, millions of people who could benefit from ART or PrEP either don’t have access to it, or choose not to take it. As long as that’s the case, the impact of the therapies will be curtailed.

Sheena McCormack, MBBS, MSc, a professor of clinical epidemiology at University College London, told MD Magazine® a number of barriers stop people from getting PrEP, including cost, time, other personal priorities, and confusion about where to go to get access. So, simplifying therapy access and reducing its costs—preferably to it being free—would address most of its barriers, she said.

“Lack of awareness or acknowledgement of risk for HIV, particularly amongst the young, is a reason people do not test for HIV—never mind about PrEP,” McCormack said. In short, clinicians need some “good old fashioned health promotion.”

Indeed, while the CDC estimates that about 1.2 million people in the US are at high risk of contracting HIV, a study released earlier this year found just 77,000 people had been prescribed PrEP. That’s way up from the 8700 people using the drug back in 2012, but still only a fraction of the number of people that would, in a perfect world, be using it.

Access Harms Ambitious Goals

The United Nations is pushing an effort to fix the problem on a global scale. Their famously lofty 90-90-90 goals call for 90% of HIV-infected people in the world to be aware of their status, 90% of people with HIV to be on sustained ART, and 90% of people with HIV to have achieved viral suppression. Perhaps most ambitiously, they hoped for these rate to be met by 2020.

The goals would be theoretically world-changing, but they’re also exceedingly unlikely to be reached on time, even in the US. In fact, the country is lagging behind in most elements of the goals, Martin Markowitz, MD, professor and clinical director at the Aaron Diamond AIDS Research Center, in New York, told MD Mag.

“We don’t do very well providing healthcare in an equitable way, in a way that people trust and understand and have access to,” he explained. In America, the people who take PrEP are primarily those with the motivation, resources, and social standing to successfully obtain access to it.

“The early adopters—most particularly Caucasian MSM (men who have sex with men)—really want to take it,” Markowitz said. “They’re the most motivated and they figure out ways to work the system.”

Others, such as people who are uninsured or have lower incomes are often less motivated to embark on what can be a lengthy fight to get their insurers to pay for PrEP. The problem is even worse in the developing world, where access to regular treatment and ART is scarce.

“The [World Health Organization] could say from today until tomorrow if prevalence is higher than 3% in any place, then you should consider PrEP,” he said. “Well, in places where they can’t afford to treat HIV-infected people how could you afford to treat them with PrEP?”

What if?

Still, the technology of ART and PrEP means there’s at least the technical capability to corner HIV. So what would happen if we achieved something like the 90-90-90 goals?

It’s not just a hypothetical. Back in 2015, investigators released results from a study of some 2000 serodiscordant couples in East Africa. The idea was to see how many people might become infected if the uninfected partner took PrEP until the viral load in the infected partner could be suppressed by ART. The 1013 couples using the PrEP/ART strategy were then compared against a simulated control group constructed based on data from a prior study of serodiscordant couples.

Patients were enrolled over the course of 2 years, and the simulation model suggested that by the end of the study phase, 21.7 infections would be reported, averaging out to 5.3 incidences of infection per 100 person-years. In reality, just a single patient became infected during the course of the study, for an actual incidence rate of 0.2 incidences per 100 person-years. PrEP was used during 47% of those 440 person-years of follow-up, and ART was used in 17% of the years. Both therapies were in simultaneous use in one-quarter of the person-years, and neither were used during 11% of the person-years of the study.

“Early results from this demonstration project integrating time-limited PrEP and ART for HIV prevention in African couples show near elimination of HIV transmission, with an observed HIV incidence <0.5% per year compared to an expected incidence >5% per year,” wrote lead author Jared Baeten, MD, PhD, of the University of Washington, and colleagues.

However, there’s a big difference between a controlled trial and the real world, McCormack noted. She agrees that if all high-risk individuals had access to PrEP, it would be a game-changer. She just doesn’t think that’s likely to happen.

“We should be able to get to zero infections that we can prevent, but the behaviors that get in the way of people looking after themselves are hard to fix,” McCormack said. “So it’s hard for me to envisage a time when we eradicate HIV [using those methods alone].”

Another barrier is the fact that “high risk” is not a static category. McCormack noted that high risk today may not be high risk in the future, “as time goes on and HIV declines in the community.”

Markowitz said geography is playing—and will continue to play&mdash;a major role in HIV outcomes. He said places with the best access and services could serve as mini-models of the potential of widespread PrEP and ART adoption.

“The likelihood that we’re going to be able to treat our way out of this is relatively low,” he said. “That said, we could do better with a focused public health effort like is being done in San Francisco, like is being done in New York.”

In some places, such as in South Africa, it will likely take a vaccine to achieve the ultimate goal of stopping HIV, she said.

Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, wrote in a 2017 editorial in the Journal of the American Medical Association that a durable end to HIV was likely impossible without a vaccine. He noted that an estimated 17 million people worldwide were infected with HIV but not receiving ART. Meanwhile, in 2016 alone, another 1.8 million people were infected with the virus.

While PrEP and ART might end HIV in a theoretical world, Fauci said a vaccine is necessary when the problem is considered from a practical standpoint. “Development of a moderately effective vaccine together with optimal implementation of existing treatment and prevention modalities could end the current HIV pandemic," Fauci wrote.

Vaccine, Not a Silver Bullet

Ironically, even if a vaccine were developed, it could potentially be limited in its impact by the same problems that restrict PrEP and ART.

“Let’s put this in context,” Markowitz said. “If you have a very effective vaccine but it is extremely costly and requires multiple injections, then it’s going to be rough, isn’t it?”

He noted that the zoster vaccine to prevent shingles is cost-prohibitive for some patients. Though the shingles vaccines on the market cost far less than ART and PrEP, they are still far out of reach for many Americans, and for the majority of people in many developing countries.

“If the vaccine is relatively inexpensive and easy to give, then yes, it will be a game changer,” he said. “But how likely is that?”

It’s unclear. Markowitz noted that a tremendous amount of money and research has already been put into the vaccine, and we remain years -- at least -- away from the finish line. In the meantime, the paradox of a functional cure but no eradication continues.

“To quote Voltaire: In the best of all possible worlds we could put this to an end,” Markowitz said. “But we don’t live in the best of all possible worlds.”

This article was originally published by MD Magazine.