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CD4 Gains on cART Lower AIDS/Death Risk Even With High Starting CD4 Count
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6th IAS Conference on HIV Pathogenesis, Treatment and Prevention, July 17-20, 2011, Rome
Mark Mascolini
Gaining more CD4 cells during suppressive combination antiretroviral therapy (cART) cut the risk of AIDS or death in a large multigroup study, as one might expect [1]. However, the impact of gaining more CD4 cells held true even in people who began cART with a CD4 count of 350 to 499 or with a count above 500.
COHERE cohort collaborators assessed the risk of progression to AIDS or death according to time-updated CD4 count in 73,336 adults who had at least two consecutive viral loads below 50 copies while taking cART, defined as 3 or more antiretrovirals of any class or combination. Follow-up stopped when a person had a viral load above 500 copies, at the first of two consecutive loads between 50 and 500 copies, or if a person interrupted cART.
Study participants had at least one confirmed sub-50 load, had a CD4 count within 6 months before the sub-50 episode or during the episode, and had data on age, gender, injection drug use, viral load, coinfection with hepatitis B or C virus, cART, and number or prior cART regimens. The primary endpoint was time to a new AIDS diagnosis or death.
The analysis included 66,147 people with a median age of 37 years (interquartile range [IQR] 32 to 44), 27% of them women, 26% ever diagnosed with AIDS, and 14% infected through injection drug use. Median initial CD4 count stood at 396 (IQR 256 to 565) and median viral load at 40,000 copies. About one third of these people (34%) were taking a nonnucleoside (NNRTI) regimen, 30% a ritonavir-boosted protease inhibitor (PI), 25% an unboosted PI, and 11% another regimen.
Three quarters of cohort members (74%) had a single sub-50 suppression episode, which lasted a median of 2.7 years (IQR 1.2 to 5.1). Only 1% of these people had a CD4 count under 50 at their first sub-50-copy reading, 15% had 50 to 199 CD4s, 26% had 20 to 349 CD4s, 25% had 350 to 499 CD4s, and 34% had 500 or more CD4s. For these CD4 brackets, AIDS-or-death rates per 1000 person-years were 94.9 for the under-50 CD4 count, 30.5 for the 50-to-199 group, 12.0 for the 200-to-349 group, 7.9 for the 350-to-349 group, and 5.2 for the 500-or-over group.
In a statistical model adjusted for other risk factors, the risk of AIDS or death per 100-CD4 cell gain was 65% lower for people with a starting CD4 count under 200, 19% lower for people with a starting count between 200 and 349, 26% lower for those with a starting count between 350 and 499, and 4% lower for those with a starting count above 500 (and that 4% was statistically significant):
Risk of AIDS or death per 100 additional CD4 cells gained on cART (with an undetectable viral load):
--Starting count below 200: hazard ratio [HR] 0.35, 95% confidence interval [CI] 0.30 to 0.40
--Starting count 200 to 349: HR 0.81, 95% CI 0.71 to 0.92
--Starting count 350 to 499: HR 0.74, 95% CI 0.66 to 0.83
--Starting count 500 or higher: HR 0.96, 95% CI 0.92 to 0.99
Risk of time to death from any cause followed a similar pattern:
Risk of death from any cause per 100 additional CD4 cells gained on cART (with an undetectable viral load):
--Starting count below 200: HR 0.32, 95% CI 0.27 to 0.39
--Starting count 200 to 349: HR 0.75, 95% CI 0.63 to 0.89
--Starting count 350 to 499: HR 0.66, 95% CI 0.58 to 0.80
--Starting count 500 or higher: HR 0.98, 95% CI 0.93 to 1.03 (not significant)
The researchers argued that the findings are robust because results held true in sensitivity analyses using different calculating methods and because of the narrow 95% confidence intervals.
"In patients on cART with HIV suppression," the COHERE team concluded, "hazards for time to progression to AIDS or death follow a CD4 cell gradient, with a CD4 cell increase giving the greatest benefit in lower CD4 cells categories but with some benefit even in those with 500 or more CD4 cells."
The investigators concluded that lack of CD4 gains in people with virologic suppression "is relevant for prognosis and poor outcome." People who begin an antiretroviral combination with fewer than 200 CD4s and do not gain CD4 cells, they advised, face an escalating risk of disease progression over time and therefore need continued medical attention--even if they reach an undetectable viral load.
Reference
1. Bucher HC, Young J, on behalf of COHERE. Risk of progression to AIDS or death in relation to CD4 cell levels in HIV-infected adults with a suppressed viral load under cART. 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention. July 17-20, 2011. Rome. Abstract WELBB01.
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