5 HIV Breakthroughs That Fell Short

Valuable Insights Gained Despite Setbacks in Research

"Breakthrough" is a word used frequently—some might say all too frequently—when describing advances in the HIV sciences. And while there have, indeed, been a number of game changers in recent years, the word often suggests that we are nearer to a cure or solution that we actually are.

This can happen when research is either misinterpreted or a reporter fails to put the science into the proper context. And that's a shame, given that what is being reported is often truly important.

Clearly, hype should never be a part of scientific reporting, something we learned back in 1984 when then-Secretary of Health and Human Services Margaret Heckler declared that we would have an HIV vaccine "within two years."

Not only do misconceptions like these erode public confidence, they often have a direct impact on public health. Numerous studies have shown that an individual’s risk perception—how much or little a person feels at risk—can be directly influenced by both the quality and source of media coverage they seek.

We saw this in 2016 when a man on the HIV pre-exposure prophylaxis (PrEP) was reported to have been infected despite taking the daily preventive therapy. Bereft of context, the reports erroneously suggested that a "rare" drug resistant strain was circulating the population, laying doubts as to whether PrEP was as viable a strategy as health officials proclaimed.

We take a look at five, recent HIV "breakthroughs" that proved to be anything but and examine what we learned, both positive and negative, in the aftermath of these setbacks.

1
AIDSVAX Vaccine

Upper angle view of scientist
gevende/istockphoto

In 1995, the AIDSVAX vaccine received enormous coverage in the media when news broke that it had provoked a defensive immune response in a small, Phase II study of human volunteers.

This led the vaccine’s manufacturer, VaxGen, to submit an application to conduct a large, Phase III human trial within the U.S.—a request that was eventually declined when it was shown that a number of volunteers had been infected during the earlier trial.

Undaunted, the VaxGen leadership appealed to the international scientific community and eventually landed a study in 2002. That trial, alas, failed to either prevent or weaken the infection among study participants.

Despite the news, the company quickly issued press releases stating that the vaccine showed efficacy in certain populations (mainly black and Asian), and even went so far as to suggest that a viable candidate could be available by as early as 2005.

Since that time, AIDSVAX has been tested in combination with another vaccine and, by 2009, the combined regimen managed to achieve 31 percent efficacy in preventing HIV.

Those results were almost immediately declared an "historic milestone" by the AIDS Vaccine Advocacy Coalition. This led to a veritable avalanche of reports suggesting that scientists were on the verge of a "functional cure" for HIV (meaning that the virus could be controlled by a vaccine rather than by pills).

These suggestions have been tamped down considerably since then, with little evidence to support the claims. Even so, a new Phase III trial began in earnest in South Africa in 2016, again using AIDSVAX and the same combination vaccine used back in 2009.

2
The Mississippi Baby

Few "breakthroughs" have garnered more media attention that the Mississippi baby, an unnamed toddler who was thought to have been cured of HIV back in 2013.

Born to an HIV-positive mother, the child was treated with an aggressive course of antiretroviral therapy 30 hours after delivery. When the child was 18 months old, the mother suddenly left care and left the child without treatment for more than five months.

When mother and child eventually returned, doctors were surprised to find that the child had no detectable virus in blood or tissue samples. This led to wild speculation that treatment delivered at the time of infection could effectively stop infection in its track.

So rampant were the beliefs, that a flood of news reports soon followed, claiming that other children had achieved the same result as a result of post-delivery therapy. (Ironically, unlike the Mississippi baby, none of these children ever had their treatment stopped for ethical reasons.)

By July 2014, at the height of the media hype, doctors reported that the virus had, indeed, returned (rebounded) in the Mississippi baby. This suggests that the virus was not eradicated as some had believed but was hidden in cellular reservoirs ready to re-emerge in absence of consistent therapy.

Studies to further investigate aggressive HIV therapy in newborns have since been postponed.

3
Replicating the Berlin Patient Cure

Timothy Ray Brown, a.k.a. The Berlin Patient, in 2012.

Timothy Ray Brown, a.k.a. the "Berlin Patient," is considered the only person to have been cured of HIV. After undergoing a highly experimental stem cell transplant from a person who was naturally resistant to HIV, Brown emerged in 2008 with no evidence of the virus in either blood or tissue samples.

The news of Brown’s cure led to subsequent studies hoping to replicate the results in others. All to date have failed.

Among them, two Boston men declared "cured" in 2013 rebounded just one year after undergoing the transplant. Some have since suggested that the latter procedure was "far gentler" than Brown’s and may account for why the virus wasn’t entirely cleared from the men’s system.

Not that stem cell transplants were ever considered a viable strategy to cure HIV. Despite the historic nature of the Berlin Patient case, the procedure itself is considered far too costly and dangerous to implement except in the most extreme medical cases.

For his part, Brown continues to remain undetectable and off therapy, although there is still debate as to whether the virus was fully eradicated or simply controlled by the transplant procedure.

Further research hopes to identify the specific mechanisms for Brown’s cure, ideally to develop tools that can used on a larger, population-based scale.

4
HIV Microbicide Setbacks

Experimental intravaginal ring employing the drug dapiravine for use as pre-exposure prophylaxis (PrEP) in women.

HIV microbicides make perfect sense. Think about it: If you were ever concerned about getting HIV from a sex partner, all you would have to do is put on a gel or cream to kill HIV on contact. How hard could it be?

But after more than 15 years of intensive research, we have yet to see a candidate able to render the kind of protection needed to achieve these goals.

One such trial, the CAPRISA 004, was touted as a "breakthrough" back in 2010 when it was shown that a gel containing a 1 percent concentration of the drug tenofovir could reduce the risk of transmission risk in women by 39 percent. For those who used the gel regularly, effectiveness could be as high as 54 percent.

But barely a year later, the National Institutes of Health discontinued a large-scale trial in Africa and India when it was shown that the same microbicidal gel had no absolutely protective benefit when compared to the placebo version.

Researchers have since provided reasons for the results, including the high prevalence of sexually transmitted infections among study participants and a high community viral load among HIV-positive men.

Ultimately, the strategy—once deemed an important step toward empowering vulnerable women and girls—fell short due to the one thing the researcher failed to consider: human nature.

According to the post-trial analysis, women (particularly young women) failed to use the gel as prescribed, often due to the disapproval of family members or fear of discovery by spouses or sex partners.

More recent investigations into the use of microbical intravaginal rings (pictured) demonstrated only moderate protection overall, while failing to provide any quantifiable protection to women 18 to 21 years of age.

5
Danish Kick-Kill Cure

National Institute of Allergies and Infectious Diseases (NIAID)

Of the examples of HIV promises that fell short, few attracted as much attention as that of Denmark’s Aarhus University when it was announced in 2013 that a cure was expected "within months."

Within hours of the announcement, the media went into a veritable frenzy, publishing reports that the Danish team was not only able to clear HIV from cellular sanctuaries (called latent reservoirs) but were able to neutralize the virus, as well. The strategy, known popularly as "kick-kill," captured the imagination of a public primed for a breakthrough following news reports about the Mississippi baby.

While the Aarhus research was, indeed, a promising step toward achieving "kick-kill," it failed to acknowledge one factor that undermined its conceit: we have yet to know even how large these reservoirs are.

It wasn’t long before news arrived that the Aarhus study fell well short of its promise, achieving modest activation of dormant viruses but nowhere near the levels needed to make"kick-kill" work.

Moreover, there is still no evidence that any agent, whether pharmaceutical or immunological, can fully eradicate HIV if released from its cellular hiding sanctuary.

Further investigations are being conducted to see whether a combination of drugs and/or vaccine agents can improve upon these early results.

Sources:

Rerks-Ngarm, S.; Pitisutithurm, P.; Nitayaphan, S.; et al. "Vaccination with ALVAC and AIDSVAX to Prevent HIV-1 Infection in Thailand." New England Journal of Medicine. December 3, 2009; 361:2209-2220.

Ledford, H. "HIV Rebound Dashes Hope of ‘Mississippi Baby’ Cure." Nature; published July 10, 2014.

Hutter, G. "Stem cell transplantation in strategies for curing HIV/AIDS." AIDS Research and Therapy. September 13, 2016; 30:13.

Centres for AIDS Programme Research in South Africa (CAPRISA). "New tenofovir gel study shows no effect on HIV prevention: Lower than expected gel use impacts FACTS trial results." Media release February 24, 2015.

United Press International (UPI). "HIV cure expected ‘within months,’ Danish scientists say." Released May 1, 2013.

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