Diseases of ageing occurring 10 to 15 years earlier in patients with HIV

The diseases of ageing develop earlier in patients with HIV than in the general population, Italian investigators report in the online edition of Clinical Infectious Diseases.

“Our findings suggest that an aggressive approach to the screening, diagnosis, and treatment of non-infectious comorbidities is warranted as part of the routine healthcare for HIV-infected patients,” comment the investigators. “Our data suggest that onset of such screening should commence at a substantially earlier age for HIV-infected persons, compared with HIV-uninfected persons, possibly at least a decade in advance.”

Effective antiretroviral therapy can significantly improve the life expectancy of patients with HIV. However, even with treatment mortality rates are still higher than those observed in the general population.

Non-infectious conditions such as cardiovascular disease, hypertension, diabetes, renal failure and liver disease are increasingly important causes of illness and death in patients with HIV. These illnesses are often associated with ageing.

This has led some investigators to suggest that patients with HIV experience premature ageing. Doctors from the Metabolic Clinic of Modena University, Italy, wanted to examine this theory. They therefore designed a study comparing the prevalence and risk factors for several common age-related conditions in their HIV-positive patients, compared to age, race and sex-matched controls.

Preliminary findings from this study were presented at the 18th Conference on Retroviruses and Opportunistic Infections in March 2011.

A total of 2854 patients who received care at the clinic between 2002 and 2009 were included in the analysis. All had experience of HIV therapy. Their mean age was 46 years, 37% were women and three-quarters had lipodystrophy – the body fat changes associated with some antiretroviral drugs. The patients were matched with 8562 controls.

The non-infectious comorbid conditions included in the analysis were cardiovascular disease, hypertension, diabetes, bone fracture, and renal failure. Data were also gathered on the prevalence of multiple conditions.

Rates of cardiovascular disease were higher among HIV-positive patients than the controls for individuals aged below 40 (0.91% vs. 0.24%, p = 0.049), as well as those between the ages of 41 and 50 (2.26% vs. 0.64%, p < 0.01), and the ages of 51 to 60 (6% vs. 2.6%; p = 0.02).

There was also a higher prevalence of hypertension in the HIV-positive patients aged over 51 compared to the controls (ages 51 to 60, 20% vs. 17%; p = 0.18; age 60+, 39% vs. 32%, p = 0.007).

In all age groups, there was a significantly higher prevalence in the HIV-positive patients of renal failure, bone fracture, and diabetes (all p < 0.001).

Moreover, across all age strata the HIV-infected patients were more likely to have multiple diseases of ageing. Strikingly, the prevalence of two or more comorbid conditions in HIV-positive patients aged between 41 and 50 was 9%, similar to the 7% prevalence observed in HIV-negative controls in the 51 to 60 age bracket.

“The prevalence…was approximately equivalent to prevalence observed in members of the public who were 10 to 15 years older,” write the authors. “We believe that, in this report, by showing the premature onset of polypathology among HIV-infected patients, we have contributed to the characterization of an emerging description of an HIV-specific aging phenotype.”

Across the entire cohort, the factors associated the presence of multiple diseases of aging were age (per 1 year increase, OR = 1.11; 95% CI, 1.10-1.12, p < 0.001), male sex (OR = 1.77; 95% CI, 1.44-2.17, p < 0.001), a lowest ever CD4 cell count below 200 cells/mm³ (OR = 4.46; 95% CI, 3.73-5.34, p < 0.001), and length of exposure to HIV therapy (OR = 1.01; 95% CI, 1.001-1.019, p = 0.001).

Further analysis also showed an association with lipodystrophy (p = 0.048).

“At any given age, HIV-infected patients had a greater likelihood of comorbidities than did control subjects,” Dr Jacqueline Capeau, the author of an editorial accompanying the study notes. “Why? Is the entire aging process accelerated in these patients? Are all HIV-infected patients aging too rapidly? What can be done?”

She suggests that the chronic inflammation and immune activation accompanying HIV infection means “patients will be more prone to develop, in advance, age-related diseases.” A low nadir CD4 cell count could further contribute to inflammatory process.

Dr Capeau also notes that the study population comprised patients treated at a metabolic clinic with a high prevalence of lipodystrophy. She suggests that these patients are likely to have been severely immune depressed when they initiated antiretroviral therapy. Moreover, their treatment would have been based on more toxic anti-HIV drugs.

“These…patients have accumulated deleterious conditions and are now affected by comorbidities,” writes Dr Capeau.

Life-style factors such as smoking, a poor diet, and drug use are also proposed as possible causes of possible causes.

“It is important to diagnose and treat these comorbid conditions,” Dr Capeau emphasises, and she proposes the wider use of anti-inflammatory drugs such as asprin and statins. In addition, “early treatment of HIV-infected patients may help to delay aging.”

Guaraldi G et al. Premature age-related comorbidities among HIV-infected persons compared with the general population. Clin Infect Dis, online edition, doi: 10.1093/cid/cir627, 2011 (click here for the free abstract).

Capeau J. Premature aging and premature age-related comorbidities in HIV-infected patients: facts and hypotheses. Clin Infect Dis, online edition, doi: 10.1093/cid/cir628, 2011 (click here for a free extract).