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Slow CD4 Gain With HAART Raises AIDS Rate 5 Times in Virologic Responders
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9th International Congress on Drug Therapy in HIV Infection, November 9-13, 2008, Glasgow
Mark Mascolini
Slow gains in CD4 cells despite full viral suppression in previously untreated people raised the rate of a new AIDS diagnosis more than 5 times--but only in the first year of a discordant CD4-RNA response [1]. After that, people who still had sluggish CD4 gains and people who gained CD4s briskly had equivalent AIDS risks in a multicenter German cohort.
The prospective ClinSurv cohort included 11,098 HIV-infected people from 12 centers at the end of 2007. This analysis focused on 1576 previously untreated people who began antiretroviral therapy with a CD4 count under 200, who had prophylaxis for Pneumocystis pneumonia, and who reached a viral load below 50 copies within 180 days of starting treatment. The investigators tracked new AIDS diagnoses that occurred more than 30 days after treatment began. Follow-up spanned the time from the first viral load below 50 copies to virologic failure, a new AIDS diagnosis, or the end of 2007, whichever came first.
The study group's age averaged 41.3 years, 80% were men, and 73% German. On average, they started antiretroviral therapy in 2001. Half had an AIDS diagnosis. Median pretreatment CD4 count stood at 63, and time to reach a viral load below 50 copies averaged 99 days. The investigators defined CD4-RNA discordance as a viral load below 50 copies with a CD4 count below 200.
In the first year of treatment ClinSurv clinicians diagnosed 42 new AIDS diseases, 27 in the CD4-RNA discordant group and 15 in the CD4-RNA responders. The most common diagnoses were malignancies (7 in discordant people and 4 in responders), tuberculosis or Mycobacterium avium complex (5 in discordant people and 3 in responders), cytomegalovirus or herpes simplex infection (3 in discordant people and 4 in responders), Pneumocystis pneumonia or toxoplasmosis (3 in discordant people and 2 in responders), and invasive candidiasis (2 in each group).
A Poisson regression model factoring in age, gender, transmission group, national origin, pretreatment CD4 count, nadir CD4 count, and calendar year of starting treatment figured that discordant responders had a 5.57 times higher rate of a new AIDS diagnosis in the first year of therapy (incidence rate ratio 5.57, 95% confidence interval [CI] 2.96 to 10.48, P < 0.001). This independently higher rate in the discordant group did not persist in year 2 or year 3 of follow-up, even though CD4 counts remained under 200 in the people analyzed.
Risk of a new AIDS diagnosis was highest in people whose CD4 count stayed under 50 (hazard ratio (HR) 6.36, 95% CI 2.53 to 15.95, P < 0.001) or below 100 (HR 3.84, 95% CI 1.70 to 8.68, P = 0.001). Variables that did not raise the risk of a new AIDS diagnosis in this analysis were a CD4 count between 100 and 200, pretreatment CD4 count, gender, age, transmission risk, and AIDS diagnosis before beginning antiretroviral therapy.
The ClinSurv clinicians called on researchers to test strategies that may boost CD4 counts faster (from Jules: IL-2 ???; IL-2 data is coming out soon) in people who start antiretrovirals with advanced disease. They speculated that prophylaxis for opportunistic infections might be suspended after 1 year of full viral load suppression, even in people with a CD4 count still below 200. But they noted that German guidelines call for prophylaxis until CD4s rise above 200.
Reference
1. Zoufaly A, Kreuzberg C, An der Heiden M, et al. Risk of new AIDS-defining events in patients with advanced immunodeficiency during suppressive HAART: results from the German ClinSurv cohort. 9th International Congress on Drug Therapy in HIV Infection, November 9-13, 2008, Glasgow. Abstract O423.
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