Is there an HIV prevention crisis?

The calculus to end the world’s HIV epidemic is, once again, proving harder than expected.

After marshaling great effort and achieving remarkable results in diagnosing HIV infections and providing life-saving antiretroviral treatment (ART) to those infected, the message from the Joint United Nations Programme on HIV/AIDS (UNAIDS) in recent years seemed to be that the road to ending AIDS was in sight, and could even be achieved by 2030. The idea was that by diagnosing and treating enough HIV-infected people, and making sure their levels of virus were sufficiently suppressed, transmission rates would tail off.

But this strategy, referred to as treatment as prevention, is more complicated than it sounds. “Easy to remember, hard to achieve,” says virologist Jeffrey Lazarus, a health systems researcher at the Barcelona Institute for Global Health.

UNAIDS and its partners set goals for treatment as prevention back in 2014 referred to as the 90-90-90 targets. The model works like this: diagnose 90 percent of all HIV-infected people, ensure 90 percent of those people receive ART, and make sure that 90 percent of those on treatment achieve viral suppression. The U.N. goal is to reach those targets by 2020, with the aim of ending HIV as a global health challenge by 2030.

But with just two years to go, only six countries—Cambodia, Denmark, Botswana, Namibia, Eswatini (formerly Swaziland), and the Netherlands—have reached those targets.

Even more concerning is the fact that in some places, HIV infection rates are increasing despite greater access to ART. That’s not all. “There are countries that have reached the targets,” Lazarus says, “but a surprisingly large percentage of people who are on treatment are not virally suppressed.”

UNAIDS officials themselves now doubt the 2020 targets will be reached and are talking about a “prevention crisis.” As outlined in a UNAIDS report, there are many contributing factors: In Eastern Europe, Central Asia, the Middle East, and North Africa, HIV incidence is on the rise; there is an ongoing global migration of refugees and asylum seekers, people fleeing both violence and poverty; and if demographic trends in Africa continue, there will be more people aged 15-35 living there by 2050 than ever before. If public health services and prevention efforts do not meet the scale of this demographic wave, new HIV infection rates could balloon.

The progress in HIV treatment is clear. More than half of the world’s 36 million people living with the virus are now on life-saving ART, and the number of AIDS-related deaths is declining, dropping 34 percent over the last seven years. In 2017, for the first time, the number of deaths from AIDS is estimated at less than a million.

But the rate of new HIV infections is not falling fast enough. While fluctuating regionally, global incidence has remained fairly steady during the last 15 years. If the number of new infections is not declining quickly enough, the number of people in need of treatment continues to grow every year.

All of these factors place the HIV/AIDS response in a precarious position. Some say an overly optimistic message instilled complacency in the global HIV response. Meanwhile, experts are calling for bolstering HIV prevention efforts and developing newer and better prevention options as a way to finally reverse the trends. “Existing HIV tools and strategies are insufficient to actually end the epidemic,” Peter Piot told a large crowd in an auditorium in Amsterdam over the summer, gathered for the International AIDS Society’s (IAS) annual meeting. Now director of the London School of Hygiene and Tropical Diseases, Piot was director of UNAIDS during a high-level meeting 15 years ago in Dublin, when there were already warning signs that Eastern Europe and Central Asia would become the fastest-growing AIDS epidemic in the world.

It did.

This, despite a 53-nation declaration pledging to scale up prevention and treatment efforts in the face of rapid crossover from high-risk groups into the general population. The number of new HIV infections in Eastern Europe was 190,000 in 2016—a 57 percent annual increase over the previous five years.

These statistics once again have the eyes of the global public health community trained on the vast landscape stretching from the Baltic to the Pacific.At the IAS conference this summer, there was a concerted effort to focus on Eastern Europe and Central Asia. Michel Kazatchkine, a onetime U.N. Special Envoy on HIV/AIDS in Eastern Europe and Central Asia, describes a situation in which many people do not know their HIV status, there is little sex education or primary prevention, and where HIV is tightly intertwined with tuberculosis and viral hepatitis. “The whole thing is very fragile,” he says. “With the huge backlog we have and the burden of disease, it will be very difficult to reverse.”

Michael Krone, executive coordinator of the Berlin-based HIV nonprofit AIDS Action Europe, sees it acutely in social terms. “The value of the lives of drug users, sex workers, gay men and other men who have sex with men, trans people, and other minorities is not estimated to be as much as those of other citizens,” he says. Data compiled by UNAIDS shows that of the 30 percent increase in new HIV infections in the region since 2010, nearly 40 percent were among injection drug users and 97 percent were among sex workers, prisoners, sexual partners or clients of sex workers, and men who have sex with men. Consistently reaching these individuals with public health or prevention and harm reduction services—needle exchange, testing and counseling, hepatitis B vaccination, treatment for tuberculosis, and HIV treatment—is difficult, and is made even more difficult because of stigma, state actions that limit access to health care services and information, and broader social pressure.

“The emerging data really call for immediate action to link and integrate HIV services with other services, particularly for people who inject drugs in the region,” says Chris Beyrer, a Johns Hopkins epidemiologist and a former IAS president. “All of this is going to be crucial for Eastern Europe and Central Asia. The work that is ahead of us is trying to do better delivering essential services to those people who need them most.”

Without a substantial investment in primary HIV prevention, particularly for key populations, young adults, and adolescents, it will be impossible to control the epidemic, analysts at the Joep Lange Institute in Amsterdam argue. “We don’t have a vaccine. But we have most of the tools: we have highly efficacious treatment, rapid HIV tests, syringe exchange, condoms, and PrEP [pre-exposure prophylaxis],” Lazarus says. “The question is, do we have the tools in Tajikistan. Do we have the tools in middle America?”

Eastern Europe is not the only obstacle to ending HIV. Sub-Saharan Africa is still home to two-thirds of the 37 million people living with HIV around the globe. Even there, where rates of new infections are falling, experts warn the situation is likely to worsen in coming years. Sub-Saharan Africa will soon have more young people than ever entering adolescence and young adulthood, Piot says. Aleya Khalifa, statistics officer for HIV/AIDS at UNICEF, has compiled data and is running models suggesting the region will be unlikely to reduce new infections in people aged 15-24 because this youth bulge will double the adolescent population by 2050. Khalifa’s modeling suggests new infections in those aged 15-19 will still be about 200,000 annually by 2030, the year targeted for ending the epidemic.

Harvard virologist Max Essex, who chairs the Botswana Harvard AIDS Institute Partnership, argues the math behind 90/90/90 makes sense and that it may just be taking time for this strategy to have its desired effect. “I’m very optimistic for places like Botswana, Namibia, South Africa, and Swaziland (now called Eswatini),” Essex says. He and a large team surveyed Botswana’s progress in achieving the 90/90/90 targets (Lancet HIV 3, e221, 2016). “The very imperfect estimates I’ve seen are compatible with incidence going down there,” he says. “Many critics misinterpret and think we should see major, statistically significant reductions in incidence within a year or two. I think this is unrealistic. I’m not a fan of the phrase ‘ending AIDS.’ It is so confusing to many.”

Reuben Granich, a Geneva-based public health consultant and former chief technical officer at the International Association of Providers of AIDS Care, worked on launching the “Fast Track Cities” program, which hinges on the 90/90/90 targets. He doesn’t think much of the “HIV response is faltering” narrative. “The recent wave of pessimism from HIV experts is a bit odd given the successes that we have seen,” he says. “We can reduce the epidemic to more manageable proportions that will then be amenable to last-mile tactics and strategies.”

Meg Doherty, the World Health Organization’s treatment and care coordinator for HIV and hepatitis, points to countries with declining HIV incidence. “Even South Africa is showing declines in incidence,” she says. But the epidemic is variable. “What we can see is there is a slowdown in [declines in] mortality and that we have to redouble our efforts and figure out why people are still dying,” she says. “It’s going to be about a few regions and a few countries. It is likely to be in more marginalized populations.”

A few years ago the infectious disease modeler David Wilson in “A Reality Check for Aspirational Targets to End HIV,” warned that if diagnosis rates and prevalence remain constant, as they have in many settings, then prevalence and incidence could actually increase while pursuing the 90-90-90 targets. “Increasing numbers of case reports and overall increases in numbers of new infections do not mean the test-and-treat strategy is failing, but simply that the strategy and targets are not consistent with large reductions in absolute numbers of new infections,” Wilson wrote (Lancet HIV, DOI:https://doi.org/10.1016/S2352-3018(14)00038-1). His view today is the same. “It is just not surprising that the global impact has not quite met what was optimistically hoped for,” Wilson says. “That there are hot and cold spots of epidemics and targeted responses is hugely important.”

Piot recognizes the need after four decades of HIV for a long-term view. “Tens of millions of people will require access to ART for decades. Decades. So, this is not going to stop in 2030,” he says. “Let’s not fool ourselves. The end of AIDS will not be possible without a vaccine. In the meantime, we will do as well as we can. The good news is that there is exciting news in terms of vaccine development, so let’s continue that effort.”

Michael Dumiak, based in Berlin, reports on global science, public health, and technology.