The future of HIV treatment, research is now at MCV
Over 1.2 million people are currently living with HIV in America. Over 619,000 have died since HIV was first observed over 30 years ago. In 1994 and 1995, HIV was the leading cause of death for Americans between the ages of 22 and 45 with over 50,000 deaths in America attributed to HIV-related illnesses in 1995 alone.
In Richmond, thousands are living with the disease and about one out of every 2,000 Richmonders is diagnosed with HIV each year. However, HIV is no longer the death sentence it once was.
Through new drugs and cutting-edge research, medical providers like the VCU HIV/AIDs Center have helped to reduce those mortality rates.
The Center treats about 3,000 HIV-infected patients with the latest in HIV treatments. Through the Center, some patients, primarily those with highly drug-resistant strains of the virus, receive access to advanced medicines before they even make it to market.
“Back in the late ’90s and early 2000s, we just didn’t have very many drugs to choose from and there was a really significant pill burden associated with HIV treatment. There were a lot of side effects, the drugs weren’t particularly potent,” said Dr. Jane Cecil, who works at the Center. She noted that new drugs have improved in almost every way over the medications of a decade ago. Therapies now have fewer side effects and are more effective at suppressing the virus. There are even “combination therapies,” like the drug Atripla, that are effective when prescribed as a single pill taken once a day.
“If they’re newly diagnosed with HIV, the majority of these patients now go on one-pill-once-a-day therapy. That’s pretty remarkable,” said Dr. Daniel Nixon, director of the VCU HIV/AIDS Center.
World Health Organization reports that since 2002, the number of people receiving antiretroviral treatment for HIV exploded by 2,216 percent between 2002 and 2010 — from 300,000 to 6.65 million.
This extensive battery of new medicines to treat HIV enables doctors to work around strains of the virus that become resistant to a certain class of drugs. Different classes attack the virus in different ways and at different stages in the virus’ development.
VCU’s Center negotiates contracts to administer medications in the advanced stages of clinical trials under closely-monitored circumstances. The drugs are usually in Phase III of the approval process, which means the medication is being administered to between 1,000 and 3,000 people to monitor side effects and confirm effectiveness. Once proven safe and effective in Phase III trials, a medicine can be considered by the U.S. Food and Drug Administration.
“(These medicines are) usually on the cusp of FDA approval, so maybe somewhere between six and 12 months in advance of what was already probably a six or eight year development process,” Nixon said.
The Center is working out the final contract now on a drug called Elvitegravir, a new one-pill-a-day version of a class of drugs called the integrase inhibitors. The drugs reduce the amount of HIV in a patient’s blood by blocking integrase, an enzyme key to HIV replication.
“If (a patient’s) virus is resistant to the existing medications, they would benefit from some of the newer things coming out and they need them sooner than later, rather than waiting on FDA approval,” Cecil said. “Treatment-experienced patients … really rely on having access to newer drugs. We can get them on newer agents that may be more effective than some of the existing drugs.”
With the growing list of effective, affordable and safe treatments, this chronic disease is becoming more manageable. Cecil said further advances in medications may reduce the frequency of medication to as little as once a week sometime in the near future. Medications are coming down the pipeline which she said have “very, very long half-lives.” The half-life of a medication is a measure of how quickly the body metabolizes, or breaks down, a medicine. If a drug is metabolized quickly, then it is only active in the body for a short amount of time. With a longer half-life, a newer drug could theoretically continue to be active in a patient’s body for a period of days or a week.
“We now have so many new drug classes available that it’s still quite easy to put together an effective regimen, even if someone’s infected with a resistant strain of virus,” Cecil said. “People can now live almost a normal lifespan with HIV, we think. We’ve now been following people for over 20 years with this infection.”
But for the most part, leading a long and healthy life with HIV involves ensuring patients are receiving the treatment — and making sure the patients are following through. Cecil said there are many obstacles to getting people with HIV into treatment.
“The biggest barrier tends to be, I would say, the stigma and the denial that goes along with finding out someone’s HIV infected. If we could get rid of that, it would take care of a lot of the problem of getting people into care,” Cecil said.
Cecil said depression and denial after an HIV positive diagnosis sometimes stand in the way of effective treatment. Other hurdles include poverty, education, substance abuse histories, mental health and the type and quality of previous healthcare, but these barriers are not insurmountable. Cecil said the level of treatment available now for HIV patients should encourage anyone with HIV to seek treatment.
“HIV’s much more treatable than most chronic illnesses because the medications are so safe, so potent, so well-tolerated and affordable now with some of the payment sources that are available for patients regardless of their economic background,” Cecil said.
Nixon said that the Center still has problems with people who don’t reliably take medications for one reason or another and a lot of resources are devoted to ensuring that patients are following through with treatment.
“We get support by the Virginia Department of Health to pay for adherence counselors who spend their time with patients trying to help them take their medicines, setting up pill boxes, reminder visits, doing pill counts,” Nixon said. “It doesn’t really matter if patients are on therapy if they’re not taking it.”
Research done at MCV has been vital to shaping national policy. The Center has participated in studies to discern when during the HIV infection is the right time to start anti-retroviral therapies.
“The Department of Health and Human Services guidelines actually have all changed as a result of a lot of that research and we’re treating people earlier and earlier now,” Cecil said.
The Center is currently involved in a National Institutes of Health study called the “Strategic Timing of Anti-Retroviral Treatment” study, or START. The initiative is a broad, multicenter trial.
Nixon said the study will go beyond the basics of a clinical trial and examine the effects of HIV and the virus’ treatment on bones, lungs and the cardiovascular and neurologic systems in detail.
“All of these are affected by HIV and potentially affected by the treatment. To answer the question of when to start (HIV treatment), you have to take a look at the whole patient and not just a few parameters,” Nixon said. “I would call it a total-body approach that looks at all the total systems and not just one or two outcomes.”
Researchers have long looked beyond regular treatment to perhaps one day curing HIV.
In very rare cases, HIV has already been cured in individuals. Timothy Brown, the famed “Berlin Patient,” received a bone marrow transplant to treat leukemia in 2006. The donor had a rare genetic mutation that prevents HIV from entering the cells. Brown, once HIV positive, has been off of antiretroviral medications for five years and doesn’t exhibit any signs of the disease. According to research presented earlier this year at the 2012 International AIDS Conference, two more patients in Boston have been treated and cured in the same way.
However, bone marrow transplants are a very high-risk treatment and only occur in situations where patients need them for reasons beyond HIV. Researchers continue to seek a better, lower-risk option for a cure. At the Center, researchers are in the very early stages of developing strategies that will attempt to seek out the virus where it hides in the body and eradicate it.
While curing the disease would be a huge victory for researchers, perhaps more important would be the ability to prevent new infections.
“There is some promise in the area of the vaccine but I think that’s still a long way off and I think more important than treatment, honestly, is prevention,” Cecil said.