SAN FRANCISCO — Antiretroviral therapy has allowed many HIV-infected people to live long enough to grow old, yet their immune systems seem to age rapidly for their chronologic age, a factor that appears to be contributing to increased risks for non-HIV diseases of aging in middle-aged patients, according to several speakers at a meeting on the medical management of HIV and AIDS sponsored by the University of California, San Francisco.
“There are striking similarities between the immune systems of some of our patients in their 50s and [those of] their parents,” said Dr. Steven G. Deeks, professor of medicine at the university.
In 2007, 28% of people living with HIV were aged 50 years or older; that proportion will grow to 50% by 2015, Dr. Richard Brooks, also of the university, said in a separate presentation.
Also at the meeting, Dr. Toby Maurer reported that her clinic is seeing more HIV-infected patients with skin diseases associated with aging, including disseminated herpes zoster and indolent Kaposi's sarcoma, despite relatively healthy CD4 counts ranging between 300 and 700 cells/mm
Disseminated zoster is “very unusual with a CD4 count of 350 cells/mm
The Kaposi's sarcoma cases are not the aggressive variety seen 20 years ago in HIV-infected patients, she said, but are the type typically found in older Mediterranean men.
To preserve immune function, Dr. Deeks advocates starting highly active antiretroviral therapy (HAART) in any HIV-infected patient who is motivated to begin treatment—a more aggressive approach than called for in treatment guidelines.
HAART reduces but does not eliminate T-cell activation and inflammation. Persistent, residual inflammation while on HAART is more extensive when patients start therapy at CD4 counts less than 200 copies/mm
Previous attempts to reduce HIV-associated immunosenescence and inflammation through the use of prednisone, hydroxyurea, cyclosporin, or mycophenolic acid were “like treating a subtle problem with sledgehammers,” Dr. Deeks said.
“We need to reduce inflammation in a safe way” through the use of statins, aspirin, exercise, omega-3 fatty acids, vitamins, and immunomodulators, he said. Newer strategies could include investigational drugs that enhance recovery of CD4 cells or that fully eradicate the subtle levels of persistent or replicating virus.
An “overwhelming amount of data” show that even patients with undetectable virus and increased CD4 counts on HAART are more likely than people without HIV to develop heart disease, non-AIDS cancer, bone disease and fractures, left ventricular dysfunction, liver or kidney failure, and frailty, Dr. Deeks said.
After controlling for the effects of other factors, including lipids or hypertension, HIV-infected patients have a 75% higher risk for cardiovascular events than do uninfected people, several studies suggest.
Dr. Brooks noted that frailty was 11 times more common in HIV-positive men, compared with HIV-negative men, in one study (J. Gerontol. A Biol. Sci. Med. Sci. 2007;62:1279–86). HIV infection of 4 years' duration or less conferred a risk for frailty in a 55-year-old man that compared with risks for a 65-year-old HIV-negative man, “confirming our impression that HIV-positive men are aging faster than their HIV-negative counterparts,” said Dr. Brooks.
To help HIV-infected patients stay healthy longer, he advised focusing on modification of traditional risk factors for non-HIV comorbidities of aging—smoking, hypertension, dyslipidemia, weight gain, diet, and exercise.
When possible, avoid HIV medications that can exacerbate illnesses associated with aging and check for drug-drug interactions, he added. Older protease inhibitors and zidovudine increase the risk for insulin resistance. Abacavir, didanosine, and protease inhibitors increase risk for cardiovascular disease. Zidovudine, protease inhibitors, and nonnucleoside reverse transcriptase inhibitors increase risk for dyslipidemia.
Dr. Deeks has been an adviser to GlaxoSmithKline and received research funds from Pfizer, Merck, Gilead, and Bristol-Myers Squibb. Dr. Maurer and Dr. Brooks reported having no conflicts of interest.