HIV infection associated with an increased risk of the diseases of ageing

HIV infection is associated with an increased risk of several diseases of old age, according to Dutch research published in the online edition of Clinical Infectious Diseases. Researchers compared the risk of cardiovascular, renal (kidney) and bone disease between older people living with HIV and matched HIV-negative controls. All diseases of ageing were more prevalent in people living with HIV, cardiovascular disease and renal dysfunction significantly so. Traditional risk factors were associated with an increased risk of these morbidities, but so too was infection with HIV, as well as longer duration of immune suppression and systemic inflammation.

“HIV-infected participants compared with uninfected controls of similar age had a significantly higher prevalence of AANCC [age-associated non-communicable co-morbidities],” comment the authors. “Our finding that co-morbidity was significantly more prevalent among HIV-positives (the majority having sustained suppression of viremia on cART) compared to uninfected controls of similar age is compatible with earlier reports.”

Improvements in treatment and care mean that many people with HIV are now living into older age. However, there is some evidence that diseases normally associated with older age develop at an earlier age in people living with HIV compared to HIV-negative individuals. The reasons for this are unclear, but may include traditional risk factors, the side-effects of some anti-HIV drugs, the inflammatory effects of HIV infection, and the damage caused by immune suppression.

In 2010, investigators in Amsterdam, The Netherlands, established a cohort to study the relationship between HIV and the diseases of ageing. In the present study, they reported two-year follow-up data comparing the prevalence of age-associated illnesses in age- and sex-matched people living with HIV and HIV-negative controls. They also examined the risk factors associated with an increased risk of age-associated co-morbidities.

The study population consisted of 540 people living with HIV and 524 people in the control group. The groups were well matched, with a median age of 52 years. The majority were male and reported sex with other men.

Approximately a third of the people living with HIV had a previous AIDS diagnosis, but virtually all were now taking antiretroviral therapy and had an undetectable viral load.

Prevalence of several cardiovascular risk factors – smoking, high blood pressure, waist-to-hip ratio, physical inactivity – was significantly higher among the people living with HIV compared to the controls.

Overall prevalence of age-related co-morbidities was significantly higher among people living with HIV than the control group (mean per patient: 1.3 vs 1.0, p < 0.001). People living with HIV were also significantly more likely to have multiple diseases of ageing (p = 0.009). In all age groups (50-55, 60-65, and over 65), the prevalence of age-related diseases was higher in the HIV-positive group than the HIV-negative group. Moreover, each age-related illness typically developed five years earlier in people living with HIV compared to their HIV-negative peers.

Each individual co-morbidity was numerically more prevalent in the HIV-positive group. In the case of hypertension (45 vs 31%, p < 0.001), heart attack (4 vs 2%, p < 0.018), peripheral artery disease (3 vs 1%, p < 0.008) and impaired renal function (4 vs 2%, p < 0.044) significantly so.

Traditional risk factors including age, smoking, family history and waist-to-hip ratio were all associated with an increased risk of co-morbidities.

HIV infection was also an independent risk factor, increasing the risk of the diseases of ageing by approximately half (OR = 1.58; 95% CI, 1.23-2.03, p < 0.001).

The investigators looked in depth at the risk factors in the HIV-positive group. They initially found that longer duration of diagnosed HIV infection (p < 0.001), duration of HIV treatment (p < 0.001) and longer time with a CD4 count below 200 cells/mm³ (p < 0.001) all increased the risk of age-associated illness. However, after controlling for potential confounders, only longer duration of immune suppression remained significant.

There was also some evidence that the risk of age-related co-morbidities was associated with markers of inflammation. “HIV infection is associated with inflammation, innate immune activation, and altered coagulation, which are generally considered important drivers for co-morbidity in both HIV-uninfected and HIV-infected individuals,” comment the authors.

Longer duration of treatment with full-dose ritonavir (Norvir) was of borderline significance.

The authors conclude that the emergence of age-related illness at an earlier age in people living with HIV “might support the hypothesis of premature or accelerated aging in HIV. Whether this reflects HIV acting as an additive risk factor for co-morbidity development in conjunction with traditional risk factors, or includes HIV impacting on and accelerating the biology of aging itself, remains to be elucidated.”