Mortality trends: why people with HIV die (or don’t) today

11 February 2006. Related: Conference reports, EACS 10 Dublin 2005.

Mark Mascolini for NATAP.org

Two big cohort studies yielded two surprises about mortality among people taking potent antiretrovirals for 5 years or more:

• CASCADE cohort researchers reported that—contrary to results of other studies—opportunistic infections remain the leading cause of death among people with HIV [1].
• APROCO and Aquitaine cohort collaborators found that people who attain and maintain a CD4 count above 500 cells/mm³ live as long as people without HIV [2].

Soaking up data from 22 cohorts of people with known HIV seroconversion dates, the CASCADE crew set out to compare causes of death in the pre-HAART era with causes since potent regimens gained wide use in developed countries. Of the 7680 cohort members included, 1962 died, 504 of them from unknown causes.

Ronald Geskus from the Health Service of Amsterdam reported that rates of progression to almost all causes of death dropped—as one would expect—since strong triple therapies arrived. After about 15 years of follow-up in both the pre-HAART and the HAART groups, opportunistic infections proved the most common killer in both eras. But cumulative incidence of death from opportunistic infection during the days of HAART was only about 25% the incidence in pre-HAART years.

After opportunistic infection the most frequent relative causes of death changed greatly when muscular regimens gained sway.

The biggest shifts in the HAART era involved a hefty relative jump in intentional and unintentional death (which are probably nice ways to say suicide and murder), a higher relative rate of death from liver failure, and a higher relative rate of death from heart disease or diabetes.

Geskus and colleagues reported that the greater relative frequency of intentional and unintentional death in the HAART epoch reflects a significant jump in such deaths among injecting drug users. They call the relative surge in liver-related deaths a nonsignificant trend.

Together the APROCO and Aquitaine cohorts embrace 1743 men and 536 women who began a PI regimen from 1997 through 1999 and logged 5 years of follow-up. Charlotte Lewden from INSERM Unit 593 in Bordeaux reported that the combined group had a median 4.4-year duration of HIV infection before treatment, a median pretreatment CD4 count of 270 cells/mm³, and a median pretreatment viral load of 4.5 log copies/mL. Lewden and colleagues documented HCV coinfection in 27% of these people, and 21% had AIDS when they started their PI.

Death rates per 100 person-years skidded from 11.3 in 1996 to 5.1 in 1997, 3.5 in 1998, 1.8 in 1999, and 1.9 in 2000. After that, though, mortality inched back up to 3.8 per 100 person-years in 2003. Lewden did not parse this uptick.

The French team figured a standardised mortality ratio as observed deaths divided by expected deaths—stratified by age and gender—with 1999 French death rates as the point of reference. The overall standardised mortality ratio showed a 7.8 times higher death risk in the HIV cohorts than in the general population and even higher risks for injecting drug users (18.6 times), women (14.1 times), and people with HCV coinfection (13.6 times).

But people with at least two recorded CD4 counts above 500 cells/mm³, no recorded count under 500 cells/mm³, and no viral load at or above 100,000 copies/mL had a standardised mortality ratio of 1.1 compared with the general population. In other words, the difference between their death rate and that of the general population—if there is a difference—must be negligible.

Lewden and coworkers argued that their findings mean HIV infection “might no longer be considered as an obstacle to obtain insurance contracts and loans” if a person reaches and keeps a CD4 count above 500 cells/mm³.

References:

1. Geskus R, Geskus R, Porter K, et al. Has effective therapy altered the spectrum of cause-specific mortality following HIV seroconversion? 10th European AIDS Conference. November 17-20, 2005. Dublin. Abstract PE18.4/6.
2. Lewden C, APROCO-COPILOTE Study Group. Responses to antiretroviral treatment over 500 CD4/mm³ reach same mortality rates as general population: APROCO and Acquitaine cohorts, France. 10th European AIDS Conference. November 17-20, 2005. Dublin. Abstract PE18.4/8.