July 22, 2010
Possibly No Survival Benefit to Starting HIV Treatment at CD4s of 500 or More
by David Evans
People who start antiretroviral therapy early—when their CD4 cell counts are 500 or greater—might not significantly lower their risk of AIDS or death over a three-year period compared with people who wait to start therapy when until their CD4 counts drop below 500. These data were presented Thursday, July 22, at the XVIII International AIDS Conference (IAC), taking place July 18 to 23 in Vienna.
In the past year, two major HIV advisory bodies—the U.S. Department of Health and Human Services HIV guidelines committee and the International AIDS Society-USA—have begun recommending that all people with CD4 counts below 500 should begin taking ARVs. Moreover, these groups also strongly urged providers to consider treating people at even higher CD4 counts.
Behind these recommendations is the growing acknowledgement that HIV is likely doing cumulative damage to the body even when CD4 counts are high. Such damage typically comes in the form of cellular inflammation, which can worsen the risk of developing cardiovascular disease and certain non-AIDS-related cancers. What remains unknown in people with high CD4 counts, however, is to what degree earlier treatment minimizes their risk for serious illness or death.
To explore this question, Joseph Eron, MD, from the University of North Carolina in Chappel Hill, and his colleagues, examined data from the CASCADE cohort study. CASCADE draws data from 23 smaller cohort studies in the United States, Europe, Australia and Canada.
The study, which began in 1996, has certain advantages over other cohort studies in terms of its ability to assess the risk of disease progression and mortality in people with HIV. Notably, unlike other studies where anyone with HIV is included, CASCADE only includes people who were recently infected with the virus. This means that researchers can more accurately assess how rapidly a person’s disease progresses following infection. It also means that when the CASCADE study looks at differences between people who start ARV treatment and those who don’t, there are less likely to be confounding factors that could skew the results.
In all, Eron and his colleagues’ analysis included data on 9,455 people who seroconverted to HIV positive between 1996 and 2008. Most were male, and the average age at seroconversion was 30 years old. Over time, 813 (8.6 percent) developed AIDS, and 544 (5.8 percent) died. The average follow-up time after seroconversion was 4.7 years.
Eron’s team broke the cohort into five groups for analysis: those with 0 to 49 CD4 cells, those with 50 to 199 cells, those with 200 to 349 cells, those with 350 to 499 cells, and those with 500 and 799. The team then tracked what happened to people if they began taking ARV treatment at each CD4 count range in a particular month at the time of that lasat CD4 count measurement or deferred treatment until a later time.
As has been documented in numerous studies, waiting to start ARV therapy is quite perilous for people who have less than 200 CD4 counts. Over a three-year period—in people with CD4 counts between 0 and 49—the cumulative risk of AIDS or death was 47 percent in people who deferred treatment compared with 17 percent in those who started. In those with CD4 counts between 50 and 199, the three-year risk was 21 percent in those who deferred therapy and 6 percent in those who started right away.
At higher CD4 counts, however, the benefits of therapy, in terms of AIDS and death rates, began to grow smaller. In those with CD4 counts between 200 and 349 who deferred treatment, the three-year cumulative AIDS or death risk was 10.3 percent, compared with 5.5 percent in those who started right away. In those with CD4 counts between 350 and 499 the difference was even smaller, 6.3 percent compared with 3.4 percent. For those with 500 or more CD4s, the difference in risk was almost identical—4.9 percent for those who waited and 5.2 percent for those who initiated treatment early.
The CASCADE data further suggest that at 350 to 499 CD4 cells, 34 people would need to be treated to prevent one new case of AIDS or death over a three-year period and that 71 would be needed to prevent one death. In those with 500 or more CD4s, there was no discernable benefit at all over the three-year period—though it is possible that a benefit would begin to become apparent over a longer period of time.
Eron acknowledged in his presentation that his group’s analysis does not take into account non-AIDS-related illness—one of the primary concerns driving the treatment guidelines changes for people with higher CD4 counts. Moreover, it is possible that people who were recorded as being on treatment actually took treatment interruptions or did not have fully suppressed virus. If this is true, it could mask the benefit of treatment, particularly at higher CD4 counts. Lastly, Eron cautioned against broadly generalizing these results for the average person living with HIV. Individualized care matters.
Search: CASCADE, early treatment, CD4, DHHS guidelines, inflammation, Joseph Eron
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