“CURE” RESEARCH HIGHLIGHTS FROM THE CROI 2014
The 21st annual Conference on Retroviruses and Opportunistic Infections (CROI) was held in Boston from March 3-6, 2014. This article will address HIV “cure” research at CROI. It is important to note that a cure for HIV is defined in two ways, a “functional cure”, currently described as disease free HIV remission without the need for antiretroviral (ARV) use and total HIV eradication from the body which is even more of a challenge. We are now working toward a “functional cure” which is much like remission in cancer cases. Even a “functional cure” will be a long time coming. But we have to start somewhere. AIDS Action Baltimore is right in the middle of “cure” research, working with government and industry as well as national and international researchers.
Last year we learned about the Mississippi Baby, the first toddler cured of HIV. The Mississippi Baby remains “cured” of HIV. The initial results were reported by our own Deborah Persaud of Johns Hopkins at CROI 2013. This year Dr. Persuad reported on another baby from Long Beach, California who is also being treated in the same manner as the Mississippi Baby. In the California case, the baby was treated four hours after birth and remains on treatment. We will not know if this very early treatment case will be successful until the child has a treatment interruption, the only way we have at this juncture to ascertain whether the baby will experience a viral load rebound while not taking ARV treatment.
This year we confirmed that the earlier you treat with ARVs, the better outcome patients will have. Research efforts to treat HIV infected babies soon after birth is underway. Results from a number of these internationally conducted trials were presented at CROI, including results from Katherine Luzuriaga of the University of Massachusetts Medical School, confirming that treating as early as possible, at least within three months of birth and even before, is better than delayed treatment.
We also know that inflammation drives HIV disease, but we don’t know the actual cause of inflammation and CD4 depletion. Michaela Muller-Trutwin from the Pasteur Institute in Paris gave a presentation that suggests caspace-3 inhibitors may have the potential to limit inflammation and CD4 depletion by activating cells that counteract the strong inflammatory responses caused by HIV.
We also learned from a presentation from Alexandra Schuetz of the Armed Forces Research Institute that treatment very soon after infection may prevent damage to the gut which causes bacteria to leak from the gut to other areas of the body, resulting in inflammation and immune activation that fuels the HIV spread of HIV throughout the body. Research efforts are ongoing to identify adults very soon after HIV infection known as the acute infection stage. Collaborations with centers conducting HIV prevention research are beginning in an effort to immediately refer acutely infected patients to research and treatment centers.
This year we learned that two Boston patients reported on at CROI 2013 that we hoped were “cured” experienced viral rebound and needed to restart ARVs. These patients had cancer like the Berlin patient, the only known adult to be “cured” of HIV. The Boston patients were given bone marrow transplants (BMTs), but their BMT donors did not carry the delta 32 genetic mutation like the Berlin patient’s donor. The delta 32 mutation is very rare and is thought to make one immune to HIV. Although this is bad news, we are in very early stages of cure research. We have much to learn. But every experiment adds to our knowledge.
HIV latency research was also a big topic of discussion at CROI. This type of research was fueled by the discovery of persisting latent pools of HIV even when people have undetectable viral loads. Latent HIV infection was discovered by our own Bob Siliciano also from Hopkins. Because latent HIV exists in the body of infected people, we are not able to “cure” HIV with only ARV use. The current research trend is to attempt to jump start latent virus, then kill it with ARVs in what is known as a “kick and kill” strategy. A number of latency studies have been undertaken with a class of drugs known as HDAC inhibitors. Like all drug research, latency questions are driven by whether a drug is safe and effective.
Regarding safety, a presentation by Thor Wagner from the University of Washington has caused some controversy. Wagner apparently believes that the “kick and kill” strategy to purge the viral reservoir will cause a proliferation of cells that may cause cancer. Many say that this is a great leap given the current data.
Sharon Lewin from Monash University in Australia showed results on nine patients treated with the HDAC inhibitor vorinistat for 14 days. She believes that the major effects of vorinistat occur very early in treatment and that thereafter mechanisms in the body take over to compensate for any such proliferation response.
A presentation from Greg Laird local rising star Johns Hopkins covered the effectiveness of a number of drugs to reverse HIV latency, including disulfiram, JQ1, bryostatin, and HDAC inhibitors, panobinostat, romidepsin, and vorinostat in resting CD4 cells taken from patients on suppressive ARV therapy. None of these drugs were able to reverse latency in any of the patient cells. In another experiment, only bryostatin was able to cause viral outgrowth, but only in certain patient cells. Many researchers believe that combinations of the drugs will be necessary to “kick” the virus out of latency and that it will also be necessary for immunomodulators like therapeutic vaccines to boost the immune system of people infected for long periods of time, the chronically infected, so that they can produce the immune system function that will be necessary to kill HIV even when ARVs are also on board.
Joe Wong from University of California San Francisco described how HIV infected DNA and RNA in the blood and in various tissue compartments acts differently, complicating matters even more. Drugs may work differently in these various compartments, requiring the use of different drugs and maybe even different doses, depending on the compartment in the body being targeted.
All the CROI “cure” research presentations demonstrate that we have a lot to learn. I am reminded of the early days of the epidemic when we first began studying AZT. We didn’t know if it was safe and effective. It took us many years to get to where we are now. There is no reason to think it won’t take many years to actually get to the point where people can control HIV replication without the need for ARVs. But the effort to cure HIV has begun and we are well on our way. Stay tuned for the latest in “cure” research.
Patient assistance and drug co-pay programs
FAIR PRICING COALITION
AIDS Action Baltimore is a prominent member of the Fair Pricing Coalition (FPC). The FPC, which was founded by the late Martin Delaney, is a national coalition of activists who work on initial HIV drug pricing issues, price increases and access to approved drugs for patients who cannot afford their medicine. The FPC also works to ensure lower prices for AIDS Drug Assistance Programs (ADAPs), Medicare, and Medicaid, as well as those who are privately insured, underinsured and uninsured.
The FPC has been negotiating with all major HIV and more recently HCV drug manufacturers to require them to institute generous and transparent free patient assistance programs for people who cannot afford their drugs and co-pay programs for people with insurance. These programs are a direct result of several years of intense work and negotiations between the FPC and representatives of the pharmaceutical industry. The FPC is now working to ensure that people with high co-insurance and deductibles are also covered under free industry patient assistance programs.
All the major HIV and HCV pharmaceutical companies now have patient assistance programs and co-pay programs. Here are links to the FPC web site where you will find links to contact information and instructions on all these industry programs and more information on the FPC and their work:
AIDS Action Baltimore (AAB) has been providing essential services to people with HIV/AIDS since 1987. Thanks to your generosity, we’re still standing after a long hard financial battle. We know only too well that times are still tough, but as we commemorate our 27th year of service, we hope we can count on your continued support which will help us maintain our many HIV/AIDS programs. We still desperately need your help to keep our doors open and continue to provide our many essential services to the Baltimore HIV/AIDS community. We hope you will remember us and continue your loyal support. Please help us in any way you can. Your donations will enable us to continue our marvelous record of benevolence and compassion with only a rate of 4.6% overhead in 2012. The amount of work we accomplish and the effect we have had on the war against HIV and HCV with only two full-time employees is truly amazing!
Although HIV disease is becoming a chronic manageable disease, here is why we still need your help now more than ever:
In the latest Centers for Disease Control data reported through June of 2012, Maryland ranked third highest in the rate of new HIV infections in the US states and territories and the fourth highest in the number of people living with HIV. The Maryland Department of Health and Mental Hygiene estimates that there are 7,400 Marylanders who are unaware that they are HIV positive.
AAB has been instrumental in organizing the community in the effort to streamline HIV testing laws and regulations so that more people can be tested for HIV. Because of AAB’s leadership in this arena, it is now much easier for people who want to be tested to do so without a lot of red tape. This will help thwart the needless spreading of HIV. Once people know they are HIV positive, they are much less likely to practice risky behavior. People also need to know they are HIV positive so that they can take advantage of all the new treatments we are helping to make available. Like all diseases, the sooner you treat HIV, the better your chances of survival.
AAB continues to provide financial assistance to many needy people with HIV/AIDS. AAB has provided this support to over 7,000 people since 1987 and over $2,700,000 in assistance to needy people with HIV/AIDS and their families in our community for items such as rent and utilities. We firmly believe we must continue our invaluable financial assistance programs. Our programs provide a safety net to people with HIV/AIDS experiencing an emergency financial crisis.
Federal money is steadily decreasing while the rate of HIV cases in Baltimore is still raging. Because federal dollars are shrinking, we need your help more than ever so that we can continue the fight to save our community from the devastation of HIV disease. AAB is also working with Senator Barbara Mikulski to ensure that the new healthcare legislation regulations will not interfere with the care and support for people with HIV provided by the Ryan White Care Act and with national advocates to ensure that all classes of antiviral HIV drugs are included on new Obama Care Act drug formularies. HIV policy gets more complicated all the time, and it is much harder every year for us to obtain the resource appropriations we need to fight the epidemic.
Our work affects all who are touched by HIV/AIDS. Eventually all people with HIV/AIDS will need new drugs for their drug cocktails when their old drugs are no longer working or because they are causing life-threatening side effects. AAB continues to work on government and industry Community Advisory Boards. We are working with the government and industry to continually change the standard of care by ensuring that their new drug pipelines remain robust, and by replacing more old toxic drugs with more effective and better tolerated drugs. We are very excited that scientists have begun to work on HIV “CURE”research. AAB is working with government and industry and the national HIV community to make a “CURE” for HIV a reality as soon as possible . AAB is a member of the new Martin Delaney Cure Research Collaboratories National Community Advisory Board and is committed to national research advocacy for better, safer new dugs and even a “CURE” for HIV although this will be a long hard road.
AAB has been instrumental in the formation of the Drug Development Committee of the AIDS Treatment Activists Coalition, a national organization that interacts with the pharmaceutical industry, pressuring companies to study drugs expeditiously and ethically and to include the HIV affected community in all aspects of research and development. AAB is also working with national coalitions like the Federal AIDS Policy Partnership and National Viral Hepatitis Roundtable, as well as the Maryland Hepatitis Coalition to obtain new money and services for people with HIV and Hepatitis C Virus (HCV) and people coinfected with HIV and HCV. HCV is a huge problem in the Baltimore metropolitan area. For example, as many as 75% of people treated for HIV at the Johns Hopkins Hospital and the University of Maryland at any given time may also be coinfected with HCV as well as HIV.
AAB is a leading member of the national Fair Pricing Coalition, working to pressure “big pharma”into pricing HIV and HCV drugs reasonably, limit price increases, cap ongoing drug prices for government AIDS Drug Assistance Programs for patients without insurance and initiate co-pay programs for patients with private insurance. At this juncture, every major HIV and HCV drug company has agreed to a co-pay program that will cover co-pay costs for people with private insurance. Our work directly affects Marylanders with ever increasing co-pays. We are also working very hard to ensure the people across the country who cannot afford their medications get their drugs free from “big pharma” through a streamlined and transparent national Patient Assistance Program (PAP). We were very successful last year in working in conjunction with the federal government and NASTAD to develop one uniform application for the various drug companies so that people need only complete one form instead of 4 or 5 different PAP applications. We are now working on a one stop shopping location so that patients can apply once for all their different HIV drugs instead of having to apply to each drug company. This year we have also convinced all major HIV drug companies to also cover some prescription costs like deductibles or co-insurance for needy people who have inadequate insurance coverage. Our work is way ahead of the curve. This type of advocacy does not happen in any other disease community.
We also maintain Project TEA Time, a new HIV prevention program for transgender people that promotes HIV testing, helps people get linked to care and treatment and remain in treatment. AAB continues to conduct community forums to educate people about new HIV and HCV drugs and research issues.
We are still doing our best to help ourselves. Thanks to the many of you who attended our recent Tea at Brookside at the home of Angie and Blake Cordish which raised over $72,000. We’re looking forward to some great new events next year. For more information on our events and the latest in HIV and HCV treatment and research information, check out our web site at www.aidsactionbaltimore.org.
Please help us to continue our emergency financial assistance programs and our vital local and national advocacy. We greatly appreciate your continued support in these tough economic times. Thank you in advance for your contribution and for your past generosity. We know you are called on to make many charitable donations. We very much appreciate your continued confidence in our work. Your donation will help us to save lives. We are forever grateful for your trust and loyal support. Remember, now more than ever, without people like you, there would be no AIDS Action Baltimore!
Lynda Dee & the AAB Board
Merle McCann, M.D., Chair
Jake Boone, III
Cameron Wolf, Ph.D., M.P.H.
Our current financial statement is available upon request by contacting AIDS Action Baltimore at 10 East Eager Street, Baltimore, MD 21202 or (410)837-2437. Documents and information submitted to the State of Maryland under the Maryland Charitable Solicitations Act are available from the Office of the Secretary of State, State House, Annapolis, MD 21401 for the cost of copying and postage.