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Increased Risk of Death for HIV+ People Mostly Due to Modifiable Risk Factors

Elevated mortality among people with HIV is largely attributable to risk factors that are modifiable before or during antiretroviral therapy (ART), according to the latest findings from the Danish HIV cohort published in the July 25, 2011, online edition of PLoS Medicine.

Niels Obel from Copenhagen University Hospital and colleagues looked at the impact of 3 factors -- response to ART, comorbidities, and drug or alcohol use -- on mortality among HIV positive people who had been on combination ART for at least 1 year.

Among Denmark's population of 5.4 million, the estimated prevalence of HIV infection among adults is 0.09%, the authors noted as background. The country's national health system provides free ART to all medically eligible HIV positive residents and enables comprehensive follow-up.

The present analysis included all 2267 HIV positive individuals in Denmark who started combination ART between January 1998 and July 2009, as well as a comparison cohort of 9068 HIV negative people matched by sex and date of birth. Study inclusion began 1 year after starting ART.

Participants were categorized into 4 four groups based on the following 3 risk factors:

• Insufficient response to ART (HIV viral load > 49 copies/mL or CD4 count < 200 cells/mm³) or presence of AIDS-defining illnesses;
• Comorbidities including hepatitis C virus (HCV) coinfection (28.2%), liver disease (39.1%), lung disease (14.8%), cardiovascular disease (7.9%), kidney disease (3.9%), diabetes (5.8%), and malignancies (16.4%);
• Drug and alcohol abuse, including having injection drug use as route of HIV transmission.

The main outcome measure was probability of survival from age 25 to 65 years.

Results

• Participants were categorized as follows:
  • 9068 individuals in control group -- HIV negative, no risk factors;
  • 871 in Group 1 -- HIV positive, no risk factors;
  • 704 in Group 2 -- HIV risk factors only;
  • 379 in Group 3 -- comorbidities with or without HIV risk factors;
  • 313 in Group 4 -- substance abuse with or without HIV risk factors and comorbidities.
• Rates of death during follow-up were:
  • HIV negative control group: 1.5%;
  • Group 1: 1.7%;
  • Group 2: 7.2%;
  • Group 3: 15.0%;
  • Group 4: 28.4%.
• Overall, HIV positive participants age 25-45 had a 8.6-fold higher risk of death, and HIV positive patients age 45-65 had a 6.0-fold higher risk, compared with HIV negative people.
• The probability of survival from age 25 to age 65 was substantially lower in HIV positive people overall compared with the control group (48% vs 88% survival).
• However, among HIV positive people with no risk factors, the probability of survival was similar to that of the HIV negative general population (86% vs 88%).
• Among HIV patients with additional risk factors, in contrast, the probability of survival was lower:
  • 58% for people with HIV risk factors only;
  • 30% for patients with comorbidities
  • 3% for patients with drug or alcohol abuse.

Based on these findings, the study authors concluded, "The increased risk of death in HIV-infected individuals is mainly attributable to risk factors that can be identified prior to or in the initial period of antiretroviral treatment. Mortality in patients without risk factors on a successful [combination ART regimen] is almost identical to that of the non-HIV-infected population."

"It has been proposed that HIV is associated with premature aging, driven by residual inflammation, even with fully suppressed viral load. Although premature aging is not a well-defined entity, it is thought to be associated with increased risk of death," they elaborated in their discussion. "As we did not observe substantially increased mortality among HIV patients without risk factors, our data does not support the theory of premature aging. Rather, the data establish that the increased risk of death in the HIV population on HAART mainly stems from classic risk factors."

"Future management of the HIV-infected population should focus on early diagnosis, timely and effective [combination ART], and treatment of comorbidity and alcohol/drug abuse," they recommended. "Serious attention should be given to non-HIV related conditions among HIV-infected persons."

Investigator affiliations: Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre Hospital, Hvidovre, Denmark; Department of Infectious Diseases, Aarhus University Hospital, Aarhus Sygehus, Aarhus, Denmark; Department of Infectious Diseases, Odense University Hospital, Odense, Denmark; Department of Infectious Diseases, Aarhus University Hospital, Aalborg Sygehus, Aalborg, Denmark; Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus Sygehus, Aarhus, Denmark; Department of Epidemiology, Boston University School of Public Health, Boston, MA.

8/16/11

Reference

N Obel, LH Omland, G Kronborg, et al. Impact of Non-HIV and HIV Risk Factors on Survival in HIV-Infected Patients on HAART: A Population-Based Nationwide Cohort Study. PLoS ONE 6(7): e22698 (full text). July 25, 2011.