TreatmentUpdate
182

2011 January 

Is HIV associated with accelerated aging of organs?

As the body ages, it naturally degrades. In the setting of HIV infection there are concerns that HIV somehow speeds up the decline of several organ systems. Researchers at the University of Modena and elsewhere in Italy have conducted a study comparing the health status of several thousand HIV-positive people with that of HIV-negative people of similar age, sex and ethnicity. Their review suggests that HIV infection appears to be associated with accelerated aging and that higher-than-normal blood pressure may be a common factor that plays a role in this problem.

Study details

Researchers recruited volunteers between 2002 and 2009:

  • 2,854 HIV-positive people taking anti-HIV therapy
  • 8,562 HIV-negative people of similar age, sex, ethnicity and geographic location

Each HIV-positive person’s medical history was matched to the medical histories of several similar HIV-negative persons whose data were used for purposes of comparison. In total, data from 11,416 people were used for this analysis.

The research team focused on the following non-infectious co-morbidities:

  • cardiovascular disease
  • type 2 diabetes
  • higher-than-normal blood pressure
  • kidney disease
  • bone fractures

The approximate profile of HIV-positive people enrolled in this study was as follows:

  • 37% females, 63% males
  • age – 46 years
  • time since diagnosis of HIV – 16 years
  • nadir (lowest-ever) CD4+ count – 170 cells
  • current CD4+ count – 544 cells
  • proportion of participants with a viral load less than 50 copies/ml – 71%

Results

Striking differences emerged between HIV-positive and HIV-negative people when researchers assessed rates of co-morbidities. For instance, co-morbidities were generally more common in HIV-positive people of a given age range than in HIV-negative people of a similar age range. Using one age range as an example, among people aged 40 years and under, cases of cardiovascular disease (heart attack, stroke), bone fractures and kidney damage were evident among some HIV-positive people but relatively absent among HIV-negative people. For all age ranges, HIV-positive people tended to have more instances of co-morbidities than HIV-negative people:

Furthermore, the risk of having two or more of the specific co-morbidities studied (referred to as polypathology by the Italian researchers) seemed to be greater in HIV-positive people than in HIV-negative people. The net effect of HIV infection was as if participants had aged by at least 10 years. For instance, the rate of two or more co-morbidities in HIV-positive people aged 41 to 50 years was equivalent to the rate seen in HIV-negative people who were aged 51 to 60 years.

Risk factors

The Italian team focused on the presence of higher-than-normal blood pressure as a key factor that seemed to link, at least in its analysis, the five major co-morbidities studied. They also found that the following factors increased the relative risk for having co-morbidities:

  • being older
  • being male
  • having a nadir CD4+ count below 200 cells

Another finding was that, in general, the longer that people took anti-HIV medicines, the greater their risk of developing co-morbidities. However, this interpretation of the researchers’ data must be taken with extreme caution because this study had a retrospective, cross-sectional design.

Such studies are prone to confounding and inadvertent bias when interpreting their results. However, conclusions from retrospective studies can be used as a guide when designing future studies with more robust statistical underpinning.

Also, because it was cross-sectional in nature, the present study used only data taken at one point in time. Thus the researchers could not assess the impact that safer, more modern anti-HIV therapies might have had compared to older therapy. Also, HIV infection causes inflammation that is only partially reduced despite the use of ART. Prolonged inflammation likely played a role in the development of some of the co-morbidities studied. Unfortunately, given the nature of the study, researchers were unable to take into account the issue of chronic inflammation.

Retrospective and cross-sectional studies are cheaper and sometimes easier to conduct than randomized, prospective and long-term studies. Thus, cost and other factors can influence study design.

The present study, despite its weaknesses, adds to the accumulating research that suggests that HIV infection and, possibly, immune deficiency appear to accelerate the aging of major organ-systems. The Italian researchers recommend that doctors caring for HIV-positive people conduct regular assessments to screen their patients for organ health so that they might prevent and treat these complications.

Future research is needed with more robust study designs to confirm and extend the present study’s findings and assess the role of severe immune deficiency.

REFERENCE:

Guaraldi G. CD4+ nadir and antiretroviral exposure predict premature polypathology onset. In: Program and abstracts of the 12th International Workshop on Adverse Drug Reactions and Comorbidities in HIV, 4-6 November 2010, London, UK. Abstract 11.