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Fast ART in Late Disease Means Slower Progression in Europe and Canada
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17th Conference on Retroviruses and Opportunistic Infections, February 16-19, 2010, San Francisco
Mark Mascolini
A retrospective review by European and Canadian researchers confirmed an earlier ACTG trial indicating that starting antiretrovirals promptly in people diagnosed with HIV and AIDS at the same time promotes slower progression to another AIDS diagnosis or death [1].
ACTG A5164 found that giving antiretrovirals within 14 days of treatment for an opportunistic disease slowed progression compared with delaying antiretrovirals until acute treatment for the opportunist ends [2]. But three quarters of the 282 people in A5164 had Pneumocystis pneumonia or bacterial infection, and the trial excluded people with Kaposi sarcoma, lymphoma, or TB.
To get a broader--if nonrandomized--look at whether fast antiretroviral intervention affects progression and survival, European and Canadian researchers assessed 646 people diagnosed with HIV from 1997 through 2004 and diagnosed with an AIDS disease from 30 days before to 14 days after HIV diagnosis. They defined immediate antiretroviral therapy as treatment begun within 30 days of the AIDS disease diagnosis and deferred therapy as treatment started from 31 to 270 days after the AIDS diagnosis. The investigators excluded people who died within 30 days of their AIDS diagnosis.
The investigators built two multivariate models to figure how immediate versus deferred antiretrovirals affect HIV disease progression. The first model factored in types of AIDS diagnoses, age, gender, HIV transmission risk group, CD4 count, and viral load at diagnosis. The second model considered all the variables weighed in the first model that remained statistically significant (P < 0.05).
The study group included 216 people diagnosed with Pneumocystis pneumonia, 143 with TB, 50 with Kaposi sarcoma, 15 with lymphoma, and 222 with other conditions. Median ages for those five groups were 39, 37, 48, 40, and 40. Respective median CD4 counts were 27, 81, 84, 109, and 30. Median viral loads were well over 100,000 copies for all groups. Eighty percent or more in each group started antiretrovirals. The immediate and deferred groups were similar in most clinical variables, except that those treated immediately were slightly older.
Models 1 and 2 both determined that deferred versus immediate treatment independently almost doubled the risk of another AIDS diagnosis or death:
· Model 1: relative hazard (RH) for progression 1.89, 95% confidence interval (CI) 1.27 to 2.82, P = 0.002
· Model 2: RH 1.85, 95% CI 1.25 to 2.73, P = 0.002
Other independent predictors of progression were Kaposi sarcoma as the AIDS diagnosis (model 1 RH 1.05, 95% CI 1.07 to 3.58, P = 0.03), lymphoma as the AIDS diagnosis (model 2 RH 2.51, 95% CI 1.01 to 6.21, P = 0.05), every older 5 years of age (model 2 RH 1.10, 95% CI 1.01 to 1.20, P = 0.02), and every 10-fold higher viral load (model 1 RH 1.26, 95% CI 1.04 to 1.52, P = 0.02; model 2 RH 1.30, 95% CI 1.08 to 1.56, P = 0.006).
The investigators noted that the low number of people with Kaposi sarcoma and lymphoma limits the ability to draw conclusions about antiretroviral timing for those diagnoses. As in any observational study, they added, unmeasured factors may affect results. The researchers also stressed that eliminating people who died quickly from the analysis means results may apply only to people who survive more than 30 days after AIDS diagnosis.
References
1. Miro J, Manzardo C, Mussini C, et al. Survival outcomes and effect of early vs deferred cART among HIV-1-infected patients diagnosed at the time of an AIDS-defining event in Europe and Canada: A Collaborative Cohort Analysis (1997 to 2004). 17th Conference on Retroviruses and Opportunistic Infections. February 16-19, 2010. San Francisco. Abstract 529.
2. Zolopa A, Andersen J, Powderly W, et al. Early antiretroviral therapy reduces AIDS progression/death in individuals with acute opportunistic infections: a multicenter randomized strategy trial. PLoS One. 2009;4(5):e5575. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0005575.
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