Written by Liz Highleyman published on HepatitisandHIV.com 9/16/15
Mortality among HIV-positive people age 50 or older has fallen dramatically since the advent of effective combination antiretroviral therapy (ART) in the mid-1990s, but even well-treated people in this age group without AIDS-defining events or comorbidities have reduced survival time, on average, compared with the general population, according to a report in the August 27 advance edition of the Journal of Acquired Immune Deficiency Syndromes.
Some recent research suggests that HIV-positive people who receive prompt treatment can reach a life expectancy similar to that of HIV-negative individuals. But outcomes may not be as good among older people with HIV. People newly diagnosed at age 50 or over are more likely to be at a later stage of infection, progress to AIDS more rapidly, and may have slower immune recovery after starting treatment than those diagnosed at younger ages. Another group of older people with HIV — those who contracted the virus early in the epidemic and survived — may have experienced serious immune deficiency before effective treatment was available and used more toxic first-generation antiretrovirals, both of which can lead to long-term negative health consequences.
Rebecca Legarth from Copenhagen University Hospital and colleagues compared long-term mortality among HIV-positive people age 50 or older in the Danish HIV Cohort Study and a matched group from the general population in Denmark, a high-income country with publicly funded universal health care, including combination ART for all HIV-positive residents.
This population-based cohort study — looking at the period from 1996, when combination ART using protease inhibitors became available, through 2014 — included 2440 HIV-positive people age 50 or over seen at 8 specialized HIV centers who were alive 1 year after HIV diagnosis. More than 80% were men, 89% were white, the median age at HIV diagnosis was 43 years, and the median CD4 T-cell count at diagnosis was 252 cells/mm3. The comparison cohort included 14,588 people in the background population individually matched (6-to-1) by age and sex.
Participants were classified as having comorbidities if they had a score of 1 point or more on the Charlson Comorbidity Index (looking at conditions including heart attacks, congestive heart failure, stroke, dementia, chronic lung disease, liver disease, kidney disease, diabetes, and cancer), were diagnosed with hepatitis C, were diagnosed with alcohol or drug abuse disorders, or were listed as injection drug users in the Danish HIV Cohort Study.
The researchers also selected a smaller cohort of 517 well-treated HIV-positive people observed during 2006-2014 who had received combination ART for at least 1 year, had HIV RNA <500 copies/mL and a CD4 cell count >350 cells/mm3 after a year on ART, and had no AIDS-defining events at study entry or comorbidities after a year on ART. In this group 86% were men, the median age was 45 years, and the median CD4 count was higher at 400 cells/mm3.
The researchers calculated all-cause mortality rates and excess mortality rates per 1000 person-years, as well as mortality rate ratios (MRRs), or the likelihood of death in the HIV-positive group compared to the general population.
- Among the 2440 HIV-positive participants, 530 (21.7%) died during the study period, as did 1388 people (9.5%) in the general population cohort.
- Estimated median survival time for HIV-positive people from age 50 onwards increased from 11.8 years during 1996-1999 to 22.8 years in 2006-2014, but remained below the 30.2 year median for the general population cohort.
- Overall MRRs decreased with increasing age, from 3.8 for people age 50-55 years to 1.6 for those age 75-80 years.
- MRRs were highest, reflecting the greatest difference in survival, during the early ART period of 1996-1999.
- For HIV-positive people observed during 2000-2005, MRRs were 1.5 for those age 50-55 years, 1.2 for 55-60 years, 1.3 for 60-65 years, 1.6 for 65-70 years, 1.9 for 70-75 years, and 1.8 for 75-80 years compared to the general population.
- In the sub-cohort of well-treated HIV-positive people without AIDS-defining events or comorbidities, median survival time from age 50 was 25.6 years, compared to 34.2 years for people in the general population without comorbidities.
- The MRR for the well-treated cohort was 1.7 compared to the general population cohort without comorbidities.
- There were no differences in mortality when HIV-positive participants were stratified by whether they were diagnosed with HIV before or after age 50.
- There were also no significant differences according to the calendar period when they were diagnosed.
“Among HIV-infected individuals estimated median survival time from age 50 years has increased by more than 10 years from 1996-1999 to 2006-2014, but is still substantially lower than in the background population,” the study authors concluded. “Even among well-treated HIV-infected individuals >50 years without comorbidity or AIDS-defining events the estimated median survival time remains lower than in the general population.”
In their discussion the researchers noted that the proportion of HIV-positive people over 50 with at least 1 comorbidity at study inclusion was higher than in the age-matched general population group. They saw a 1.6-fold increased risk of death of among HIV-positive participants without comorbidities compared to people in the general population without comorbidities.
As a limitation, they explained that excluding HIV-positive people who died within the first year after HIV diagnosis — a group more likely to have advanced HIV disease and comorbidities — meant that the study cohort was healthier than an unselected population of HIV-positive people over 50.
R Legarth, MG Ahlström, G Kronborg, et al. Long-term mortality in HIV-infected individuals 50 years or older: a nationwide, population-based cohort study. Journal of Acquired Immune Deficiency Syndromes. August 27, 2015 (online ahead of print).