HIV comes of age as disease of mid-to-late life

Protease inhibitors revolutionized HIV management, morphing it from a death sentence to a chronic, manageable condition. Medical issues have since grown more complex as doctors consider how HIV interacts with aging, and how aging interacts with these sometimes toxic drugs used to control the virus.

In some respects, the HIV clinic run by J. Michael Kilby, MD, FACP, is starting to look more like a clinic for older adults.

Over 300 of the roughly 1,000 HIV patients treated at the Medical University of South Carolina in Charleston are at least 50 years old, said Dr. Kilby, who directs the division of infectious diseases there. Some of the patients have been diagnosed in midlife or beyond. In other circumstances, they've lived with the virus, sometimes at undetectable levels, for a decade or more.

HIV specialist Donna Sweet MD MACP treats a patient with HIV She hopes to boost the number of primary care physicians prepared to handle all medical issues virus-related or not for this group of
HIV specialist Donna Sweet, MD, MACP, treats a patient with HIV. She hopes to boost the number of primary care physicians prepared to handle all medical issues, virus-related or not, for this group of patients. Photo courtesy of Kansas University School of Medicine

“So we are dealing with something that we weren't planning ahead for,” he said. “It's a happy dilemma to be in.”

More than 15 years after the first protease inhibitors were approved, revolutionizing HIV medicine and abruptly commuting many death sentences, the immune system disorder has morphed into a chronic condition. As a result, the medical issues involved have gotten both simpler and more complex for primary care physicians caring for patients who happen to have HIV.

To a large extent, the virus is easier than ever to control, particularly if it's diagnosed early and hasn't developed resistance. The latest first-line regimens require fewer pills, sometimes only taken once daily, and have limited side effects compared with prior generations of drugs, Dr. Kilby said. An HIV diagnosis these days triggers some of the same emotional and lifestyle challenges as, for example, a diagnosis of type 1 diabetes, he said.

It might require some time to absorb the news and perhaps incorporate the assistance of a support group. “But it doesn't mean it's time to make funeral preparations,” he said. “It means you have to commit to a lifetime of learning to manage your disease.”

Longer survival, though, also means that doctors are learning firsthand how HIV interacts with the aging process, along with other complexities, such as the cumulative impact on the body of years of taking sometimes toxic medications, according to HIV specialists.

Primary care physicians may be assuming a larger role with these patients, as the first generation of HIV specialists retires and relatively few are training to fill their places, according to an Institute of Medicine report about access to HIV care released earlier this year.

The report's authors call for more efforts to train and support primary care doctors, particularly in the outpatient setting where the bulk of HIV care occurs. Also this year, the American College of Physicians Foundation launched a three-year workforce initiative funded by a $2.9 million grant from Bristol-Myers Squibb to improve HIV expertise among primary care doctors.

Ironically, as HIV has become more of a chronic condition, it's not as exciting to doctors as they choose a medical specialty, said Donna Sweet, MD, MACP, a credentialed HIV specialist and steering committee chair of the ACP Foundation initiative.

By pairing physician mentors with interested primary care doctors and outpatient clinics through the workforce initiative, Dr. Sweet, professor of medicine at the University of Kansas School of Medicine in Wichita, hopes to boost the number of physicians prepared to handle all medical issues, virus-related or not, for a patient with HIV.

“People who do primary care medicine can do HIV medicine with some tutelage on the HIV component,” said Dr. Sweet.

Aging HIV

From 2006 through 2009, the number of Americans diagnosed with HIV has remained relatively steady at 50,000 annually, according to the latest data from the Centers for Disease Control and Prevention (CDC), published in August. Gay men are more likely to be diagnosed, comprising 61% of the new HIV infections in 2009. About 27% of new cases involve heterosexual men and women; the remainder is linked to a mix of risk factors, including injection drug use.

At the same time, the face of HIV is aging, according to another CDC report analyzing data from 2005. The analysis found that 15% of new HIV or AIDS diagnoses occurred in adults ages 50 and older. That age group also represented 24% of all those living with the immune disorder compared with 17% in 2001.

The prognosis has never been better following an early diagnosis, Dr. Sweet said. “There are unfortunately many clinicians who do not understand that if you find a 20-year-old right now and treat him or her how they should be treated, and they take care of themselves the way they should, those people can expect to live to be 70.”

A Lancet study, published in 2008, highlighted the improved effectiveness of medication over a 10-year span. A 20-year-old diagnosed from 1996 to 1999 could expect to live an average of 36.1 additional years compared with 49.4 years if diagnosed from 2003 to 2005.

The analysis, based on more than 43,000 patients in North America and Europe, also illustrated the relevance of a patient's baseline CD4 cell count prior to starting combination therapy. If a 20-year-old's count fell below 100 cells/µL, the projected life expectancy was an additional 32.4 years compared with 50.4 years if the CD4 count exceeded 200 cells/µL.

But not every HIV patient who walks into a doctor's office has followed an optimal treatment path, Dr. Kilby said. “In the real world, people don't take their medicines reliably and a lot of people suffer the consequences, he said. Even if it was erratic adherence from years ago, they suffer the consequences of it now.

Another potential challenge faces patients who may be coping with differing complications, depending on which medications they've been taking and for how long. For example, a patient who began therapy in the early 1990s may be coping with adverse effects, such as neuropathy or lipodystrophy, associated with the less tolerable regimens commonly used then, Dr. Kilby said.

Meanwhile, doctors must watch out for other diseases common in later life, such as hypertension, diabetes and osteoporosis, among others, some of which may be more likely with HIV. Eric Christoff, MD, ACP Member, alerts his medical school students that HIV must be considered an inherent risk factor for heart disease.

“What I tell them is, ‘Think of the HIV patient in terms of coronary disease risk the same way you've been thinking of diabetics,’” he said.

An HIV diagnosis doesn't necessarily complicate treatment for common conditions like hypertension or diabetes, said Dr. Christoff, an internal medicine physician and HIV/AIDS specialist at Northwestern Memorial Hospital in Chicago. But it makes addressing those conditions even “more pressing,” he said.

Referring out?

Dr. Sweet, a general internist who diagnosed her first AIDS patient in 1983, continues to care for a mix of HIV and non-HIV patients, a model that she hopes to foster in other primary care practices. Her Wichita practice, built over 30 years, includes two nurse practitioners and a physician assistant along with other support staff, such as case managers.

As she describes it, HIV is one of a number of chronic diseases she monitors in patients, more often than not through regular checkups. In one day she may see a dozen patients with HIV/AIDS, checking on their medication adherence, running their HIV bloodwork, keeping up with their various Pap smears and other screening tests, giving flu shots, and so on. “And then they make another appointment in three to four months,” she said.

Primary care doctors or clinics, with some mentorship or training, could easily handle these types of patients, referring out if they encounter some complexity, such as a multi-drug-resistant virus, Dr. Sweet said. As an analogy, she pointed out that a patient with stable heart disease typically is monitored by a primary care doctor rather than a cardiologist.

The goal of the ACP Foundation workforce initiative is to assist doctors not only with the latest HIV care protocols but also with handling some of the related psychosocial concerns and taking advantage of available funding streams.

Along with the federal Ryan White HIV/AIDS Program (the largest provider of services for people living with HIV/AIDS in the U.S.), there are state drug assistance programs—albeit increasingly strapped these days—and pharmaceutical assistance programs, among others.

Dr. Sweet, who wants ACP Foundation's initiative to start training doctors before year's end, already informally mentors a Wyoming family physician, who has assumed the care of roughly two dozen HIV patients. “When I go up there, she pulls out her charts and we go through her ‘problem children,’” Dr. Sweet said.

Mental adherence

Once the virus is under control, an HIV patient's needs mirror those of others in the same age group, with some exceptions. Mental health symptoms, for example, are more common. Dr. Christoff said that he's become more aggressive in the last year or so about referring patients to psychologists when mental health concerns arise. That additional step provides some peace of mind, he said, that those needs are being better addressed than during a time-pressed primary care physician visit.

A 2008 study in JAIDS: Journal of Acquired Immune Deficiency Syndromes involving 3,359 HIV patients found that 42% had been diagnosed with depression. Michael Horberg, MD, MAS, FACP, a study author and director of HIV/AIDS for Kaiser Permanente, described that figure as conservative. “The likelihood is that other patients had depression, but it wasn't identified,” he said.

Patients with HIV can develop depression unrelated to their diagnosis, Dr. Horberg said. They also might develop symptoms in the wake of the diagnosis or, alternatively, unidentified depression may have led to unsafe sex and other risk-taking behaviors that made them vulnerable to HIV in the first place.

Regardless, tackling depression also appears to help keep HIV management on track. Dr. Horberg's 2008 study, which tracked CD4 and RNA levels, determined that depressed patients with HIV who took a selective serotonin reuptake inhibitor had blood results similar to those of HIV-positive patients who weren't depressed.

Forecasting longevity

As people continue to grow old with the virus, some unique opportunities will develop to study how HIV interacts with the aging process and vice versa, Dr. Kilby said. After all, as the body ages, the immune system becomes inherently more vulnerable.

It's unclear, if a patient develops kidney or heart failure or dementia, “Were you prone to have that anyway?” he asked. “Or did you have an additive factor because of your chronic HIV disease?”

Some research shows that even patients with undetectable virus levels carry higher inflammatory markers than the general population, Dr. Kilby said. The body is successfully controlling the HIV infection, he said, “but there is a cost potentially to that.”

Dr. Christoff, while acknowledging the encouraging data regarding longevity, counted himself among those doctors who aren't convinced that even the best controlled patient receiving optimal care for HIV and any other conditions can anticipate the same lifespan as someone who doesn't carry the virus.

But if primary care doctors do their jobs right, going beyond HIV care to address high cholesterol and other risk factors, such as smoking, then today's patient might get close, he said.

“If the patient says, ‘Am I going to live a normal lifespan?,’ The short answer is, ‘Probably not quite that long. But if you make the right choices and decisions, it's probably going to be almost that long.’”