The past year brought no major breakthroughs in the search for an HIV cure, but a growing understanding of how the virus hides in the body is bringing people closer to strategies for long-term remission, researchers and advocates said at the 2017 HIV Cure Summit.
Since its founding in December 2015 with a $20 million grant from amfAR, the Institute for HIV Cure Research at UCSF has hosted an annual forum to mark World AIDS Day. Compared with past summits, this year's meeting focused less on nitty-gritty laboratory research and more on community participation in cure research.
"It is so important for the community to be involved in cure research so that they have the latest accurate information and reasonable expectations, especially if they want to volunteer to participate in HIV cure trials," Lynda Dee of the AIDS Treatment Activist Coalition, who spoke at the summit, told the Bay Area Reporter. "Personally, I believe it is also vital for the community to advocate for continued funding for all areas of HIV research, including cure research, as all things HIV are under a budget attack by the current administration."
Early treatment reduces reservoir of the virus
Summit participants heard about a case of HIV remission in a San Francisco man, Clark Hawley, who started antiretroviral treatment very soon after infection, shedding light on what might be needed to achieve a functional cure. Hawley has decided to be open about his experience and spoke at the summit in the hope of helping others. Another cure research participant, Luis Canales, also described his experience.
To date, only one person - former San Francisco resident Timothy Ray Brown, known as the Berlin Patient - appears to have been truly cured of HIV. Ten years after receiving bone marrow transplants to treat leukemia from a donor with a natural mutation that makes T-cells resistant to HIV infection, extensive testing has found no detectable functional virus in his blood or tissue samples.
Researchers have followed a number of cases over the years of people who appear to maintain control over HIV. Some have detectable virus but their immune system seems to be able to keep it in check naturally without antiretrovirals. Other individuals on treatment have reached the point where they had no detectable HIV according to the most sensitive tests, but the virus came roaring back when they tried stopping treatment.
As described in a special HIV edition of PLoS Medicine, Hawley, 54, enrolled in a PrEP demonstration project and started Truvada (tenofovir/emtricitabine). But it was later determined that he had very early HIV infection, during the "window period" when the so-called HIV reservoir is becoming established in CD4 T-cells and there is not yet enough of an immune response to produce antibodies against the virus.
When he had a detectable viral load test a week after starting PrEP, Hawley stepped up to a four-drug antiretroviral regimen, as Truvada alone is not enough to suppress the virus over the long term.
Study authors Dr. Timothy Henrich and Dr. Steve Deeks of UCSF and colleagues said that, to the best of their knowledge, this is the earliest documented case of HIV infection in an adult followed by immediate initiation of antiretroviral therapy (except for post-exposure prophylaxis, which involves starting preventive treatment after a known HIV exposure). San Francisco's RAPID program successfully gets people on treatment within days after diagnosis, but diagnosis typically does not happen immediately after infection.
Over the next three years, the researchers were unable to detect HIV in Hawley's blood plasma, brain fluid, samples of gut, lymph node, and bone marrow tissue, or in more than 500 million CD4 T-cells.
After 34 months on continuous antiretroviral therapy, Hawley decided to try a closely monitored treatment interruption. After stopping therapy his HIV remained undetectable for 225 days - around seven and a half months - but it then reappeared, rising steeply to nearly 80,000 copies. This is similar to the duration of off-treatment remission Henrich previously reported in a Boston bone marrow transplant recipient. Hawley went back on treatment, re-suppressed the virus, and is doing well.
This resurgence likely indicates that a rare residual virus became active and encountered no strong immune response to keep it in check, according to Deeks.
"By the time [Clark] stopped therapy, we think he had about 200 [HIV-infected T-cells] - that's a million-fold reduction in the amount of virus a typical person has," Deeks said. "It didn't cure him, but it got close, and it provided us a pathway to see what a near cure looks like. But at the end of the day, a low reservoir is insufficient, and we're going to need to stimulate the immune system at the same time."
Added Heinrich, "His case is important as it demonstrates that extremely early initiation of antiretroviral therapy can have a profound effect at limiting the overall burden of residual disease. Although early therapy did not completely abort or eradicate infection, it led to prolonged antiretroviral free remission."
To move forward, cure research will depend on people like Brown and Hawley, who will undergo extensive testing to look for residual virus, as well as individuals who are willing to interrupt treatment to see if experimental therapies can keep HIV under control without the help of daily antiretrovirals.
But this strategy is risky. Although study participants are monitored frequently, as soon as HIV starts replicating it can cause damage that is hard to undo. And anyone who stops treatment can lose their "undetectable equals untransmittable" status, with resurgent viral load putting their sex partners at risk of infection.
While there is ongoing debate within the community about whether treatment interruption studies and other types of cure research are ethical, a recent survey found that a substantial proportion of people living with HIV are willing to participate.
"One of the most encouraging things [in the HIV cure field] is that people living with HIV - including those who have had the infection for decades and have been through holy hell and back - are still willing to participate in these sometimes very intrusive studies and contribute to science for the health and well-being of not just themselves, but of people who haven't even been infected yet," science and policy consultant Judith Auerbach said at a summit media briefing.
Hawley offers a perfect example.
"When I was presented with the information that I was among the earliest detected HIV cases ever, and they felt they could learn a lot for the sake of humanity, I just agreed," he told the B.A.R. "When this started there was no one else's body that could give the researchers the information that mine could. When they tell you that you are the only person in the world where the disease was caught this early, and in a place where extensive testing is possible, it is far easier to step up and do what I can."