AIDS 2012: Looking back on D.C. and ahead to Melbourne
analysis by Stephen LeBlanc
Three issues that promise possibly dramatic shifts in the fight against HIV came to the fore at the 2012 XIX International AIDS Conference last month in Washington, D.C.
First was the new focus on finding a cure for HIV.
"I think the most exciting development at this conference was the broad community buy-in to pursuing AIDS cure research," explained Dr. Steven Deeks of UCSF.
Deeks cited a number of cure-related research findings presented at the conference and at the pre-conference AIDS cure research symposia of particular interest.
"Dr. Timothy Henrich of Harvard presented data about two HIV-positive patients who received stem-cell bone-marrow transplants to treat cancers and are now possibly HIV-free, though they are still taking AIDS drugs," he said.
Unlike the Timothy Brown case, the donors were not genetically resistant to HIV infection. This suggests that transplant itself, under the cover of anti-HIV medicines, could in some instances cure HIV.
"Charline Bacchus presented updated information about the Visconti cohort in France that shows that these patients have different immunological characteristics than elite controllers, so it appears that something else happened in the patients, possibly as a result of their early treatment, that is allowing their immune system to suppress the virus without drugs," Deeks explained.
Being able to induce the body to suppress HIV long term without drugs is the working definition of a functional cure, and researchers hope that studying how this happened in that cohort might lead to a therapy that works in patients who are not necessarily treated during acute infection.
However, it was also apparent that funding for cure research lags far behind other AIDS Research areas. Dr. Anthony Fauci of the National Institutes of Health displayed a pie chart showing a breakdown of AIDS research spending at the NIH plenary session. Of a total 2012 NIH AIDS research budget of over $3 billion, approximately $862 million was directed to the basic science areas of etiology and pathogenesis; $625 million to vaccines; $169 million to microbicides; $494 million to behavioral and social sciences; $81 million to treatment as prevention; $692 million to drug discovery, development, and treatment; $251 million to training and infrastructure; $308 million to natural history and epidemiology; and $64 million to information dissemination. Cure research did not appear as a slice of the chart.
NIH has released figures indicating that even with recently announced increases, AIDS cure research is funded at about $75 million annually, or less than 3 percent of total NIH AIDS research spending. The AIDS Policy Project, a group of cure activists, publicized the slogan "3 percent is not enough," and released a report calling for increased funding for AIDS cure research.
Some political leaders have stepped up to change the funding outlook for cure research. At the end of the conference, Representatives Barbara Lee (D-Oakland) and Jim Himes (D-Connecticut) introduced House Bill 6187, which would provide $100 million over five years for cure research. The funding would come out of a health section of the defense budget, rather than NIH funding.
Treatment as prevention
Treatment as prevention moved from being a somewhat controversial idea in San Francisco when discussed two years ago to becoming a widely accepted central plank of the global strategy to end AIDS. Treatment as prevention was cited as another strong motivation for the United Nations global AIDS target to get 15 million people on HIV treatment by 2015. Doing so, however, will require substantial increases in global funding for AIDS treatment, and clear sources for these funds have yet to be identified.
The federal Food and Drug Administration approved Truvada as a pre-exposure prophylaxis (PrEP) daily pill for at-risk HIV-negative persons just before the AIDS conference took place. That was also cited as a potentially major new development, and one that could have immediate effect for Californians.
Five different California pilot studies will begin soon to determine interest in and effectiveness of taking daily PrEP in real-world clinical settings, with community clinical health sites in San Francisco, Los Angeles, Long Beach, San Diego, and Oakland/Richmond. The trials have some slight differences, but each will provide PrEP medication free for volunteer enrollees for approximately one year and follow the enrollees carefully to assess the effectiveness of the new prevention strategy. People whose only HIV risk is injection drug use are not currently eligible for any of the pilot programs, as Truvada has not be definitively proven effective in that population.
Dr. Albert Liu, director of HIV prevention intervention studies for the San Francisco Department of Public Health, is the principal investigator for the San Francisco pilot project, which will be located at City Clinic, 356 7th Street (between Folsom and Harrison) in SOMA and begin in September.
"We plan to enroll 300 volunteers who are either HIV uninfected MSMs (men who have sex with men) or trans women," said Liu. "We are studying who will be interested in taking PrEP in a [sexually transmitted infection] clinic setting, how PrEP will work in a busy public health clinic, and adherence issues in a more real world setting."
DPH will publish a telephone number when enrollment begins for those interested in the study, and volunteers can also be recruited directly from City Clinic or referred by any doctor or other public health clinic. This pilot study is funded by NIH. DPH is coordinating another arm of the study in Miami, with public health officials there expect to enroll 200 participants.
The University of California's HIV/AIDS Research Program (CHRP) is funding four additional California PrEP studies. According to CHRP director George Lemp, "We are sponsoring several research teams that will be providing PrEP to up to 700 volunteers in Los Angeles, San Diego, and Long Beach."
According to Lemp, the studies are being supported by CHRP with $11.8 million in funding from grants over the next four years. A further pilot study sponsored by CHRP is being planned that will include a number of sites in Oakland and Richmond and is lead by Dr. Jeffrey Burac at Alta Bates. This study will focus on reaching young MSM and trans women of color, with a target of 50 percent African American enrollees.
Both Liu and Lemp stressed that that PrEP is likely to have the biggest impact when used with other strategies as part of a comprehensive prevention package.
"We are interested in offering PrEP for HIV-negative persons in combination with testing and linkage to care plus treatment (TLC+) for HIV-positive persons so that when we engage an at-risk HIV community we have options available to keep HIV infected people healthy and keep uninfected people uninfected," said Lemp.
Both also stressed that daily adherence is a key issue for effective PrEP. All of the studies will include adherence evaluations, counseling, and different adherence assistance strategies. According to Lemp, the Los Angeles portion of the study will uniquely provide real time drug level monitoring at each clinic visit to help determine whether volunteers are taking the drugs regularly enough to maintain effective blood levels for HIV prevention and will share those results with volunteers and use them to guide adherence support interventions.
One potential concern is that people who become HIV infected while taking PrEP might quickly develop virus that is resistant to Truvada, one of the most widely prescribed anti-HIV drugs. According to Liu, previous studies have shown that among people who became infected while taking PrEP there was no evidence of resistance in those cases. However, there were individuals who were already acutely infected when they began taking PrEP and tested positive a month later and there was evidence of some resistance to one of the two drugs (FTC) in the PrEP pill.
The City Clinic study is planning to do a rapid HIV test, a fourth generation HIV test that is more sensitive, and a symptoms clinical evaluation for acute infection before starting volunteers on PrEP to ensure no one in the acute infection stage starts on PrEP. The trial will also do a pooled HIV RNA viral load test on subgroups of patients, and then test every patient if a pooled subgroup tests positive. Gilead, the manufacturer of Truvada, is providing drug free of charge for the California pilot studies.
The next International AIDS Conference will be held in 2014 in Melbourne, Australia. Its local co-chair, Professor Sharon Lewin of Monash University, has been involved in cure-related research for several years.
"My impression is that we are at a totally different space with regards to cure research than we were two years ago at the time of the Vienna AIDS conference," Lewin said. "I gave a plenary talk on cure research in Vienna and the level of knowledge was just really, really low. The level of knowledge and interest has just grown exponentially in the last two years."
Lewin is looking forward to welcoming the international AIDS community to Melbourne in 2014 and hopes for further advances by that time.
"We should have the results of a large number of pilot and investigational studies relating to different cure strategies by that time and I hope have a clearer picture of the most promising avenues for cure therapies."
Stephen LeBlanc is a board member of the AIDS Policy Project. He attended the AIDS conference on behalf of the Bay Area Reporter and filed this report.