The risk of having more comorbidities increases with age, smoking, duration of ART use, and the severity of previous immunodeficiency, Judith Schouten, MD, from the Department of Neurology at the Academic Medical Center and the Amsterdam Institute for Global Health and Development in the Netherlands, reported here at the AIDS 2012: XIX International AIDS Conference.

In October 2010, Dr. Schouten and colleagues began an ongoing prospective comparative cohort study to determine the prevalence of and risk factors for age-associated noncommunicable comorbidities (AANCCs).

For this analysis, the outcome measure was the number of AANCCs per participant. The participants self-reported most of the AANCCs on a questionnaire, but some were determined using objective assessment or laboratory tests.

Study participants are 45 years or older. There were differences between the 489 people in the HIV-positive group and the 452 people in the HIV-negative (control) group in terms of age (52.9 vs 51.5 years; P = .009), the proportion of males (89.4% vs 83.8%; P = .013), and the proportion Dutch people (75.1% vs 82.1%; P = .037). The proportion of men sleeping with men was similar in the 2 groups (68.5% vs 63.5%; P = .105).

Subjects in the HIV-positive group had been seropositive for a median of 12.2 years, and the 91.2% of the group receiving ART had been receiving it for a median of 11.2 years. They were doing relatively well; mean CD4-positive T cell count was 573 cells/μL, and 85% had undetectable viral loads in the year prior to enrollment. Thirty percent had a history of AIDS.

Smoking was more prevalent in the HIV-positive group than in the control group (31.9% vs 23.9%; P = .006), but there were more heavy drinkers in the control group (3.5% vs 6.9%; P = .019). There were also statistically significant differences between the HIV-positive and control groups in terms of body mass index (24.1 vs 24.5 kg/m²) and blood pressure (135/82 vs 133/79 mm Hg).

More Comorbidities at Earlier Ages in the HIV-Positive Group

Dr. Schouten reported that 60% of the control group had at least 1 comorbidity, compared with 74% of the HIV-positive group. The mean number of comorbidities was 1.4 in the HIV-positive group and 0.9 in the control group. In addition, "each HIV-positive age category has a higher mean number of comorbidities than the 5-year HIV-negative age category."

Subjects in the HIV-positive group developed more AANCCs earlier than those in the control group. For example, in the HIV-positive group, there was a mean of 1.52 AANCCs in the 55- to 60-year age group; in the control group, there was a mean of 1.47 AANCCs in the 65 and older group.

Cardiovascular diseases were significantly more prevalent in the HIV-positive group, as were chronic liver disease, reduced renal function, and several types of cancers.

On multivariate regression analysis, age (odds ratio [OR], 1.5 per 5.0 years) and smoking (OR, 1.1 per 5.0 pack-years) were independent risk factors for comorbidities, as was duration of HIV infection (OR, 1.2 per 5.0 years of infection).

When duration of ART was added to the model, the odds ratios for age, sex (OR, 1.0), and smoking remained fairly stable, "however, the odds ratio for HIV duration shifted toward 1.0," and the OR for duration of ART shifted toward 1.35 per 5.0 years, Dr. Schouten reported.

She cautioned that the duration of ART is known with more accuracy than the duration of HIV, "making ART duration a stronger variable in itself. We also have to take into account that the vast majority of our cohort — over 90% — is on treatment."

Glycation Endproducts Linked to Comorbidities

Advanced glycation endproducts (AGEs) are the result of the nonenzymatic glycation of proteins, lipids, and DNA. Their accumulation is influenced by age (rising with advancing age), smoking, inflammation, renal function, and diabetes. The level in skin can be measured quickly and easily with an instrument that measures skin autofluorescence.

When the investigators included AGEs in the multivariate models, they found that all the ORs for the previous risk factors remained fairly stable, but "excess AGE accumulation seemed to be an independent risk factor for comorbidity," she said.

Dr. Schouten explained that in subjects of a similar age, comorbidities were more prevalent in the HIV-positive group than in the control group, and that a longer duration of infection and of ART were associated with a higher prevalence of AANCCs.

In addition, there was consistently an excess accumulation of AGEs in the HIV-positive group, which was independently associated with a higher prevalence of AANCCs.

Dr. Schouten cautioned that causality cannot be established with this cross-sectional analysis, but she hopes that future analyses of longitudinal data from this ongoing study will shed light on the role of AGEs.

Session moderator Grace McComsey, MD, professor of medicine and pediatrics at Case Western Reserve University and division chief of pediatric infectious diseases and rheumatology at University Hospitals of Cleveland in Ohio, told Medscape Medical News that she appreciates the information on elevated levels of AGEs. She explained that AGEs in the absence of HIV infection have been shown to be independent risk factors for cardiovascular disease.

"If you account for everything else, people with high AGEs have a higher risk of cardiovascular disease, and that has never been studied in HIV," she said. "It's definitely something new. It's one of multiple biomarkers of cardiovascular disease, but because the HIV population is aging...it's important to look at it."

Dr. McComsey pointed out that there have been large studies outside of HIV showing that AGEs correlate with several different markers of cardiovascular disease.

"What do we do in patients who are suppressed taking their medications? What can we do to decrease inflammation, immune activation, and oxidative stress? I think all of these things have to be studied in the relevant population, which is virally suppressed patients," she said.

The study did not receive any commercial funding. Dr. Schouten reports receiving travel grants from some commercial entities. Dr. McComsey reports consulting for Bristol-Myers Squibb, GSK, and Pfizer.

By Daniel M. Keller, PhD

AIDS 2012: XIX International AIDS Conference: Abstract THAB0205. Presented July 26, 2012.