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No Evidence of Premature Aging Effect in HIV-Positive Patients

By Satyajit Das

May/June 2013

Similar to some other conditions including diabetes, hyperlipidaemia and rheumatoid arthritis, HIV-positive people are at higher risk of developing serious age-related co-morbidities including myocardial infarction and kidney and liver disease. It is still unclear whether HIV-positive patients experience these conditions at similar or younger ages compared to HIV-negative individuals and this is often discussed under the contentious concept of accelerated and premature aging.

Keri Althoff and colleagues from the Veterans Aging Cohort Study (VACS) compared mean age at diagnosis for myocardial infarction (MI), end stage renal disease (ESRD) and non AIDS defining cancers, and also compared their incidence by HIV status.1

Premature aging was defined as differences in mean age at MI, ESRD and cancer diagnosis. All analysis were adjusted for race, sex and body mass index (BMI), alcohol use, cigarette smoking, hepatitis C infection, anaemia and diabetes. Myocardial infarction and end stage renal disease analysis only were adjusted for hyperlipidaemia, lipid lowering medication, hypertension, anti hypertensive medications and statin use.

The analysis was based on data collected from 2003 to 2008 on >100,000 patients with HIV-positive cases matched by age, race and ethnicity 1:2 to HIV-negative controls from the same cohort. HCV was more common in HIV-positive people (35% vs 15%) but diabetes (17% vs 25%), hypertension (25% vs 38%) and dyslipidaemia (36% vs 44%) was more common in HIV-negative people.

In the HIV-positive group, 19% had a CD4 count <200 cells/mm3, 61% had undetectable viral load (<500 copies/mL) and 25% had an AIDS diagnosis. PI-based and NNRTI-based were each used by about 45% of people on ART. Mean age was 55 (+/- 8) years.

Mean age for each of the primary endpoints are detailed in Table 1 and although incidence rates remained higher for HIV-positive vs. -negative people, there were no differences in the adjusted analyses for age at diagnoses for MI and ESRD with the marginally lower age for cancers (0.7 years) unlikely to have clinical significance.

In conclusion HIV-positive individuals had a greater rate of MI, ESRD and HIV associated cancers compared to HIV-negative individuals.

There was no difference in mean age or adjusted mean age at MI and ESRD by HIV status. There was a modest difference at the age of non AIDS defining cancers in HIV patients (about 6 months younger in HIV-positive groups). There was higher incidence of Hodgkin's disease but over all no difference in the incidences of other HIV associated or non-AIDS defining cancer rates in HIV patients.


Table 1: Mean Age at Diagnosis and Adjusted Rates by HIV Status
 HIV pos (yrs)HIV neg (yrs)adj. mean difference, years (95% CI)aIRR vs HIV neg (95% CI)
MI 55.3 55.3 -0.04

(-0.62, +0.64)

1.81

(1.49, 2.20)

ESRD 55.3 58.5 -0.23

(-0.69, +0.23)

1.43

(1.22, 1.66)

HIV-related cancer ** 54.9 57.8 -0.57

(-0.93, -0.21)

1.84

(1.62, 2.09)

Other cancers 58.5 58.7 -0.45

(-0.78, -0.12)

0.95

(0.85, 1.06)

** HIV-associated cancers were defined as anal, lung, liver and oral/pharynx cancers and Hodgkin lymphoma.


Even when a small age difference was found, the different risk factors and pathogenesis in HIV-positive people are likely to explain this which is very different to the less scientific concept of premature aging.

An analysis by Kathy Petoumenos from DAD group also found limited evidence of accelerated risk of cardiovascular disease (CVD) in HIV-positive patients.2

The study hypothesised that accelerated aging in HIV-positive patients would mean an accelerating risk of CVD with older age, and that the increased risk per year older would be higher in D:A:D relative to the results from risk equations developed for the general population (Frammingham, CUORE, ASSIGN). The researchers included 24,323 men (man age 41 years) prospectively followed in the D:A:D study (approximately 139,000 patient years of follow up) who had data collected on conventional CVD risk factors but who had no prior CVD events.

Primary events included 474 MIs, 683 cases of coronary heart disease and 884 cases of cardiovascular disease events. Crude event rates for each of these endpoints was 2.29, 3.11 and 3.65 per 1000 PYFU at age 40-45 and 6.53, 11.91 and 15.89 at age 60-65 years. They showed that there was a slowly accelerating risk of cardiovascular disease for year older and which was somewhat raised compared to the general population based on the equations for cardiovascular disease. The relative risk with MI was not different between D:A:D and the general population. The researchers did not find evidence of accelerating risk of cardiovascular disease with age in their study population.


Comment

Adjustment for younger age of HIV cohorts compared to HIV-negative general population controls appears to explain much of the difference seen in studies that previously reported younger age at diagnosis of non-AIDS events in HIV-positive people.


References

Unless stated otherwise, all references are to the Programme and Abstracts of the 20th Conference on Retroviruses and Opportunistic Infections, 3-6 March 2013, Altanta, GA.

  1. Keri Althoff et al. for Veterans Aging Cohort Study. HIV+ adults are at greater risk for myocardial infarction, non-AIDS cancer, and end-stage renal disease, but events occur at similar ages compared to HIV- adults. 20th CROI, 2013 Atlanta, USA, Abstract 59. Atlanta, USA. First presentation.
  2. Petoumenos K et al. Increased risk of cardiovascular disease with age in men: a comparison of D:A:D with HIV- cardiovascular disease risk equations. 20th CROI, Atlanta, 2013. Oral abstract 61. Third presentation.

Links to other websites are current at date of posting but not maintained.

Satyajit Das is with University Hospital Coventry.




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