The success of breakthrough HIV drugs means one of the biggest challenges in the decades to come will be treating HIV as part of the aging process. More than half of all people with HIV in the United States are over 50, and by 2030 it is estimated that this figure will rise to 70 percent, according to the International Society for Infectious Diseases. Older HIV patients will be in general decline, while also battling conditions caused by decades of HIV drug use.
"This is a new frontier for a lot of us," said Kelsey Louie, chief executive officer at nonprofit Gay Men's Health Crisis. "People are living longer with HIV, so we are dealing with things we haven't had to deal with before, like the long-term effects of medication," he said. "It's important to understand that people who are aging will be facing other health issues that will only be complicated by HIV."
The economic toll of HIV in the U.S. keeps rising. This year federal funding for the disease has reached $27.5 billion. Today there are more than 1.2 million people in the United States living with HIV. More than 700,000 people with AIDS have died since the beginning of the crisis, according to data compiled by the Centers for Disease Control and Prevention. In 2014, there were 12,333 deaths (due to any cause) of people with diagnosed HIV infection ever classified as AIDS, and 6,721 deaths were attributed directly to HIV, according to the CDC. Doctors and drug companies are pursuing new approaches to treatment.
"We are at a fork in the road," said Greg Millet, vice president and director of public policy at AIDS nonprofit amfAR, who previously worked on AIDS and aging as a government epidemiologist during the Obama administration. "The fact that people living with HIV are living longer is fantastic news for many of us coming up in the era of the '80s and '90s, when it was effectively a death sentence and people did not live beyond five to 10 years," he said.
Eric Sawyer, age 62, a long-term HIV activist and consultant at the New York City-based GMHC, knows all too well the toll that these lifesaving medications can take on the body. Sawyer started developing symptoms of HIV back in 1981, even before the virus was discovered. At the time, he was told that he wouldn't live to see age 35. Fortunately, he was able to enroll in some of the earliest clinical trials taking place in HIV medical research. He has taken part in testing for a host of HIV drugs over the years.
While these drugs helped save Sawyer's life, some of the drugs he took came with debilitating side effects. One drug played a role in his developing peripheral neuropathy, which causes severe pain in his feet. To this day, Sawyer can't wear regular shoes. Years later Sawyer developed avascular necrosis of the hip. "My hip started to crumble, and I had to have a hip replacement in my 40s and the other hip replaced a couple of years ago."
The development of this type of necrosis can arise from the use of anabolic steroids that physicians often prescribe to people living with HIV to help them to gain weight, or from medications currently being prescribed to treat the disease, said Dr. Bisher Akil, a New York City-based physician who treats Sawyer.
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About five years ago Akil started Sawyer on an antiretroviral medication called Truvada, developed by Gilead Sciences. Today's HIV antiretroviral drug regimens are taken in pill form, as part of a three-drug treatment regime that work together as a cocktail to block the HIV-virus at different parts of the replication cycle. This approach stops the virus from infecting new cells and allows a patient's T-cell count to replenish. These drugs have proven so successful they can reduce the amount of the HIV virus detectable in the body to a degree that it is no longer measurable by a blood test.
Truvada worked well for Sawyer, but the medication may also have played a role in causing a severe level of toxicity in his kidneys, which left untreated can result in renal failure. To stop the elevation of serum creatinine levels in Sawyer's blood, which was causing damage to his kidneys, Akil took Sawyer off Truvada and replaced it with Gilead's newer version of the drug, Descovy, which received the Food and Drug Administration's approval in April 2016.
Descovy, a combination of the drugs emtricitabine and tenofovir alafenamide (TAF), can be given at a much lower dose than Truvada. Several of Gilead's newer HIV drug therapies, such as Genvoya and Odefsey, contain TAF in place of tenofovir disoproxil fumarate (TDF), which is the main ingredient in Gilead's older HIV drugs — Stribild, Atripla and Complera, as well as Truvada.
TAF has demonstrated that it works as well as TDF-based drugs at less than one-tenth the dosage. It has also demonstrated improvements in renal and bone safety. Patients in a trial on a TAF-based drug had less hip and spine bone loss and more favorable kidney function than those on TDF-based drugs, according to Gilead.
Descovy has an average wholesale price of near-$1,800 a month, similar to Truvada's price, according to pricing information from the National Institutes of Health. Sawyer's doctor said paying for Descovy would be cheaper for the health insurance provider than paying for Sawyer to go on dialysis or get a kidney transplant, which is where Sawyer was headed. After six months on Descovy, Sawyer's kidney function improved.
This switch to newer drugs is beginning to show up in Gilead's results. In its quarterly earnings released last week, overall HIV drug sales increased by 12 percent, to $3.4 billion, in the fourth quarter 2016, even as Truvada sales and sales of other, older TDF-based HIV drugs continued to decline. HIV sales totaled $12.9 billion for the full year 2016, also up from the previous year's level of $11.1 billion.
AmfAR's Millet said HIV and related drug therapies have been shown to accelerate the aging process with issues including the onset of kidney and liver disease, bone loss and osteoporosis and cognitive impairment.
"We need to start focusing on these other issues. … There is not enough medical literature on common geriatric drugs and HIV drugs," he said. Millet added that the issue is not only whether HIV drugs and other geriatric drugs could interact negatively but whether other drugs could suppress the HIV drug regimen. There is also evidence that HIV-positive individuals develop an immune system that is described as "hyper vigilant" for an extended period of time, and in older people that can lead to chronic inflammatory conditions.
ViiV Healthcare is close to releasing new HIV medications that could do less harm to older HIV patients by replace the three- and four-drug "cocktail" many HIV patients are on with a two-drug therapy. The UK-based joint venture of Pfizer, GlaxoSmithKline and Japan's Shionogi & Co. released Phase III clinical trial results this week for one of its new two-drug therapies.
John Pottage Jr., chief scientific and medical officer at ViiV Healthcare, said two drugs is the lowest number needed to inhibit the virus at different parts of its replication cycle. "If you are thinking about patient care over the long term, you want to be able to individualize the care of patients and provide for future options that may come with less side effects," he said. A two-drug therapy may do just that. "It goes back to having choices for patients," Pottage said.
Pottage said the prognosis for these new therapies is promising and the company expects to file with the FDA for approval in mid-2017. If all goes well, ViiV Healthcare will bring at least one two-drug HIV-treatment combinations to market in 2018, per FDA approval. The company will be filing in other countries and regions around the world as well.
ViiV is also working with Johnson & Johnson's Janssen to develop a once-a-month injection for patients who have already achieved HIV-viral suppression through a daily pill regimen.The injectables would be given as an intramuscular shot that releases the medication out into the body over a period of time, a dramatic change in the way antiretroviral treatment is administered. The pharma company has started a Phase III trial and will evaluate the data in 2018 with the hope of submitting it for FDA approval in 2019.
Competition between drug developers remains fierce, but Pottage said that all new discoveries are welcome, in particular by physicians. "When you are taking care of patients for their life, you don't want to only be able to offer them just one medicine. You may need to change the medications and dosage to see which drugs are more tolerable," Pottage said. "You have to take a long view, and be able to switch medications, whenever necessary."
Millet agreed. "Providing choices of drugs is one of the best ways to suit what is best for patients," he said. For some that may be to continue taking a daily dosage of pills. But cognitive impairment could make it more difficult for older HIV patients to manage their prescriptions, creating a need for a delivery option, like injectables.
Millet said research into long-term injectables would help the HIV population on both ends of the demographic curve: the youngest HIV-positive individuals are by far the largest group of new cases, as well as undiagnosed cases.
The annual number of new HIV diagnoses in the United States from 2005 to 2014 declined by 19 percent, but as many as 50,000 new cases are diagnosed each year, according to recent CDC annual data. Thirty-seven percent of the 39,513 new HIV cases in 2015 were among people age 20 to 29, the largest group of new diagnoses; four percent of cases were those 13 to 19 in age, according to the CDC. The number of news cases among individuals 39 or younger was 65 percent in 2015.
"This would be very helpful for young people, as they are less likely to adhere to medication," Millet said. It would not only help young HIV patients to suppress the virus but would reduce the number of new cases. Millet said there is also ongoing research into HIV drug implants, which could function similar to birth control and work for as long as a year.
In New York City the number of new HIV diagnoses has decreased in all age groups over the past five years, and that means that everyone living with HIV is living longer, said Dr. Demetre Daskalakis, assistant commissioner of the Bureau of HIV/AIDS Prevention and Control at the NYC Health Department.
"The overall epidemic is aging because of population dynamics," Demetre said, but he added that new HIV diagnoses are indeed concentrated among young persons. In 2015, 36 percent and 26 percent of new diagnoses in New York City were among persons age 20 to 29 and 30 to 39, respectively.
Younger individuals "are still the leading edge of the epidemic – where the most sexual activity is taking place and where the lowest levels of viral suppression have been achieved," he said. Sixty-six percent of all persons 20 to 29 are virally suppressed, whereas 86 percent of persons over the age of 60 are virally suppressed.
"These factors create the 'perfect storm' for the ongoing epidemic among younger persons," Demetre said. "Younger individuals did not experience the period of the HIV epidemic in which people with HIV were dying in great numbers due to a lack of treatment options. This can make it difficult to communicate the urgency of HIV prevention efforts."
"Long-term injectables are incredibly promising," Millet said. But he stressed one point about current HIV drugs that should not be lost as research into new drugs proceeds: "The first-line medication are easily the best ever. These are remarkably effective, with very few side effects."
— By Leslie Kramer, special to CNBC.com