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Starting ART at Higher CD4 Count Lowers Nucleoside Toxicity Risk
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4th IAS Conference on HIV Pathogenesis, Treatment, and Prevention
July 22-25, 2007
Sydney, Australia
Mark Mascolini
Starting antiretroviral therapy (ART) at progressively higher CD4 counts cut the risk of nucleoside analog side effects, according to analysis of the US HIV Outpatient Study (HOPS) cohort [1]. The HOPS team also found that the risk of three major nucleoside toxicities dropped over time if they did not emerge in the first year of therapy.
HOPS began enrolling HIV-infected people at several US sites in 1993. The nuke toxicity analysis involved patients analyzed for development of three classic side effectsÑ1969 people with peripheral neuropathy, 1398 with anemia, and 1152 with renal insufficiency. The HOPS team grouped them by pre-ART CD4 count (0 to 49, 50 to 199, 200 to 349, 350 to 499, and 500 or more). Median follow-up measured 3.1 years in the neuropathy group, 4.3 years in the anemia group, and 4.5 years in the renal problem group.
Multivariate analysis determined that starting ART at a CD4 count under 200 independently raised the risk of peripheral neuropathy 1.54 times (P < 0.001), the risk of anemia 1.58 times (P = 0.030), and the risk of renal insufficiency 2.22 times (P < 0.001). Starting treatment with a CD4 count at or above 350 trimmed the risk of neuropathy 12% and the risk of anemia 27%, but these risk improvements fell short of statistical significance (P = 0.437 and P = 0.165).
Other independent predictors of neuropathy were every extra 10 years of age, which upped the odds 39% (hazard ratio [HR] 1.39, P < 0.001) and use of d4T (HR 2.16, P < 0.001) or ddI (HR 1.34, P = 0.023). Being male lowered the risk of anemia 47% (HR 0.53, P = 0.017), while AZT use almost doubled the risk (HR 1.93, P = 0.017). Every extra 10 years of age boosted the chance of renal insufficiency 50% (HR 1.50, P = 0.003), being male cut the risk 44% (HR 0.56, P = 0.025), and being white almost halved the risk (HR 0.54, P = 0.010). AZT therapy doubled the risk of kidney problems (HR 2.02, P = 0.005), but taking tenofovir did not.
A separate analysis of 895 people compared rates of neuropathy, anemia, and renal insufficiency in those who began ART within a certain CD4 bracket with rates in people who delayed starting therapy until the next lower CD4 bracket. People who began treatment in each higher CD4 stratum almost always had lower side effect rates per 100 person-years than people who delayed. (The one exception was anemia among people who started with 200 to 349 CD4s versus fewer than 200 CD4s.) But none of these differences reached statistical significance.
These three side effects never developed in more than 80% of the HOPS cohort. When they did, the toxicities almost always appeared within the first 6 to 12 months of therapy. If a side effect did not crop up in the first year of treatment, the chance that it emerged later dropped with continued nucleoside use.
Reference
1. Lichtenstein K, Armon C, Moorman A, et al. Initiation of antiretroviral therapy at higher CD4+ T cell counts reduces incidence of nucleoside analogue toxicities acutely and risk for later development with continued use of these agents in the HIV outpatient (HOPS) cohort. 4th IAS Conference on HIV Pathogenesis, Treatment, and Prevention. July 22-25, 2007. Sydney. Abstract MOPEB016.
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