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CD4 Counts Predict Non-AIDS Disease Risk in FIRST Trial
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Mark Mascolini
February 26, 2007
14th Conference on Retroviruses and Opportunistic Infections
Los Angeles
Low CD4 counts predicted not only AIDS progression, but non-AIDS heart and liver disease and non-AIDS cancers in the FIRST trial of different antiretroviral strategies for treatment-naive people [1]. Jason Baker (University of Minnesota) cautioned Retrovirus Conference attendees that these results may apply only to people who begin antiretrovirals at low CD4 counts, as most FIRST enrollees did.
Last year the SMART study of CD4-guided treatment breaks linked that tactic to a heightened risk of non-AIDS diagnoses [2]. To probe for potential ties between CD4 counts and non-AIDS diseases, Baker and FIRST colleagues tracked non-AIDS diagnoses in previously untreated people randomized to a protease inhibitor regimen, a nonnucleoside regimen, or a triple-class regimen.
For purposes of this analysis, cardiovascular disease included myocardial infarction, stroke, or coronary artery disease requiring surgery; liver disease included cirrhosis and grade 4 transaminase climbs; renal disease meant end-stage renal disease or renal insufficiency; and cancer meant any cancer except Kaposi sarcoma and non-Hodgkin lymphoma.
As the FIRST team already reported, median CD4 count at study entry measured a relatively low 163 cells [3]. After a median follow-up of 5 years, a protease inhibitor plus two nucleosides or a nonnucleoside plus two nucleosides performed similarly in preventing HIV disease progression and maintaining CD4 counts. Triple-class regimens did not improve those outcomes.
At the 5-year follow-up point, FIRST researchers counted 226 new AIDS-defining diagnoses and 166 new non-AIDS diagnoses, including 86 people with liver disease, 38 with kidney disease, 32 with a non-AIDS cancer, and 21 with heart disease. A multivariate analysis adjusted for age, gender, race, prior AIDS, hepatitis B or C, baseline viral load and CD4 count, and latest viral load determined that every extra 100 cells in the latest CD4 count lowered the risk of an AIDS diagnosis 42% (hazard ratio [HR] 0.58, P < 0.01) while cutting the risk of a non-AIDS diagnosis 19% (HR 0.81, P < 0.01).
Risk of liver disease dropped 24% with every 100 more cells in the latest CD4 count (P < 0.01), risk of heart disease dropped 22% (P = 0.06), and risk of a non-AIDS cancer fell 17% (P = 0.08). The latter two findings fell just short of statistical significance. A higher CD4 count appeared not to protect against kidney disease in this population.
Because the latest CD4 count predicted odds of non-AIDS progression after adjustment for other risk factors, the FIRST team proposed that "treatment strategies minimizing the time spent at lower CD4 counts will prevent both OD and non-OD events."
References
1. Baker J, Peng G, Rapkin J, et al. HIV-related immune suppression after ART
predicts risk of non-opportunistic diseases: results from the FIRST study. 14th Conference on Retroviruses and Opportunistic Infections. February 25-28, 2007. Los Angeles. Abstract 37.
2. The Strategies for Management of Antiretroviral Therapy (SMART) Study Group. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med. 2006;355:2283-2296.
3. MacArthur RD, Novak RM, Peng G, et al. A comparison of three highly active antiretroviral treatment strategies consisting of non-nucleoside reverse transcriptase inhibitors, protease inhibitors, or both in the presence of nucleoside reverse transcriptase inhibitors as initial therapy (CPCRA 058 FIRST study): a long-term randomised trial. Lancet 2006;368:2125-2135.
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