Comorbidity Burden in People With HIV Tied to Increased Mortality Risk

The prevalence of comorbidities in people with HIV on effective antiretroviral treatment was consistently higher compared with HIV-negative individuals, and was linked to an increased risk for death, according to a prospective longitudinal cohort study.

In people age 45 and older followed for a median 5.9 years, 5.2% of the 596 HIV-positive participants died compared with 1.3% of 550 HIV-negative participants, reported Eveline Verheij, MD, of Amsterdam University Medical Centres, and colleagues.

Twenty-four of the 31 deaths in the HIV-positive group were from aging-associated comorbidities (none were from AIDS), as compared with two of seven deaths in participants without HIV. Of these, deaths from non-AIDS-related malignancies occurred in 15 and one individual, respectively.

Of note, while the HIV group started with a higher comorbidity burden, the mean number of comorbidities then increased at similar rates between the two groups over time, with a rate ratio (RR) of 1.04 per year for HIV-positive participants (95% CI 1.00-1.08) and an RR of 1.05 per year for HIV-negative participants (95% CI 1.01-1.08, P=0.78 for interaction), they noted in The Lancet HIV.

Each additional comorbidity was associated with an increased risk of death (HR 3.33, 95% CI 2.27-4.88, P<0.0001).

"Our findings highlight the need for strategies to optimize prevention, screening, and early intervention for aging-associated comorbidities and non-AIDS malignancies, particularly for long-term survivors with HIV as they age," Verheij and colleagues wrote.

"Despite awareness about the increased risk of comorbidities, uptake of preventive strategies is not optimal and should be improved, such as for cardiovascular risk management," they noted. "None of the cancer screening programs, except those concerning anogenital cancers, include indications for increased screening in people with HIV, despite increasing evidence for increased cancer risk in these individuals."

Verheij and team assessed disability-adjusted life-years (DALYs) calculated in 2-year intervals over the study period. Mean DALYs increased by 0.209 per year in HIV-positive people versus 0.091 per year in HIV-negative people (P=0.0045 for interaction), though this difference was reduced when deaths were excluded in establishing DALYs (0.127 vs 0.066, P=0.11 for interaction).

In an accompanying comment, Reena Rajasuriar, MPharm, PhD, and Pui Li Wong, MBChB, MRCP, of the Centre of Excellence for Research in AIDS at the University of Malaya in Kuala Lumpur, Malaysia, noted that the study has both immediate and long-term implications.

"Although not part of the analysis in this study and rightly acknowledged as a limitation by the authors, is the consideration of the effects of social determinants of health and stigma on the outcomes of disease burden in people with HIV," they wrote. "Both disproportionately affect people with HIV and are substantial barriers to healthcare access. How much of the increased DALY observed in people with HIV could be attributed to these determinants should be a consideration in future studies."

For this study, Verheij and colleagues included 596 HIV-positive participants from the HIV outpatient clinic of the Amsterdam University Medical Centres and 550 HIV-negative participants from the sexual health clinic and the Amsterdam Cohort Studies at the Public Health Service of Amsterdam, who were enrolled from Oct. 29, 2010 to Oct. 9, 2012.

Participants had to be at least 45 years of age, and HIV-negative patients had to have a documented negative antibody test.

Mean age was 52 in both groups, and the majority were male at birth. Most participants were white.

The median age of HIV-positive participants who died was higher than those who did not die. Positive participants who died also had more pack-years of smoking and were more frail. They also had a lower mean nadir CD4 count at enrollment and more often had a history of AIDS and use of toxic nucleoside-analogue reverse transcriptase inhibitors. Moreover, those who died were more likely to have sought care later than those who didn't die.

Verheij and team noted that most of the HIV-positive participants in the study had been diagnosed many years before enrollment and many had had severe immunodeficiency or AIDS, so results might not be generalizable to patients who are diagnosed quickly and start antiretroviral treatment immediately with newer regimens.

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