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Poor CD4 Responders Have Almost Doubled Risk of Non-AIDS Disease
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XIX International AIDS Conference, July 22-27, 2012, Washington, DC
Mark Mascolini
Adults who reach an undetectable viral load with their first antiretroviral combination but fail to boost their CD4 count above 200 within 15 months had almost a doubled risk of serious non-AIDS diseases in a 1228-person analysis of the Italian MASTER Cohort [1]. A new AIDS disease more than doubled chances that a non-AIDS disease would develop.
Previous research found that poor CD4 gains despite a good virologic response to antiretroviral therapy (ART) make AIDS or death more likely. For example, a prior MASTER Cohort analysis of 751 people starting ART with a CD4 count below 200 figured that every 10-fold higher CD4 count during follow-up halved the risk of a new AIDS disease or death (hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.41 to 0.64, P < 0.001) [2].
But the impact of poor CD4 response on non-AIDS diseases had not been closely studied until the new MASTER Cohort analysis [1]. Focusing on poor CD4 responders, the researchers tabulated on-treatment non-AIDS diseases, defined as malignancies, severe non-AIDS infections, renal failure (confirmed estimated glomerular filtration rate below 30), cardiovascular events, liver disease, acute pancreatitis, or non-AIDS-related death. Patients stopped contributing to the analysis if they stopped ART, had a viral load above 50 copies for 180 days or more, or died because of AIDS.
The 1228 study participants had fewer than 200 CD4 cells when they started their first ART and had a confirmed viral load below 50 copies within 15 months of starting. The researchers defined CD4 nonresponse as a count below 200 after 15 months of treatment.
About three quarters of study participants were men, 55% had a clinical AIDS diagnosis, and about one quarter were injection drug users. Median pretreatment CD4 count was 76.5 (interquartile range [IQR] 28 to 142). After 1 year of treatment the median count climbed to 286 (IQR 197 to 387), but 319 people (26%) still had a count under 200.
Median follow-up was 3 years (IQR 1.3 to 6.1). After 1 year of follow-up, the MASTER team counted 102 new non-AIDS diagnoses, 25 of them malignancies, 21 severe infections, 19 renal, 16 cardiovascular, 9 hepatic, 6 other nonfatal illnesses, and 6 deaths due to other non-AIDS causes. During the same period, clinicians made 70 new AIDS diagnoses. The non-AIDS diagnosis rate was 2.13 per 100 person-years, meaning a serious non-AIDS disease developed in about 2 of 100 people every year.
In univariate analysis, CD4 nonresponse raised the risk of a non-AIDS diagnosis 85% (HR 1.85, 95% CI 1.22 to 2.79, P = 0.004). Other significant predictors were older age (HR 1.03 per year, 95% CI 1.01 to 1.05, P = 0.005), injection drug use (HR 1.63, 95% CI 1.04 to 2.56, P = 0.034), and hepatitis coinfection (HR 1.95, 95% CI 1.17 to 3.23, P = 0.010).
After statistical adjustment for baseline traits, CD4 nonresponse almost doubled the risk of a serious new non-AIDS diagnosis (adjusted hazard ratio [aHR] 1.96, 95% CI 1.21 to 3.19, P = 0.006). An AIDS disease developing during follow-up more than doubled the risk of a serious non-AIDS disease (aHR 2.29, 95% CI 1.30 to 4.05, P < 0.004). A separate statistical analysis that considered an AIDS diagnosis as a time-varying covariate determined that CD4 nonresponse raised the risk of a serious non-AIDS diagnosis 86% (aHR 1.86, 95% CI 1.14 to 3.04, P = 0.013).
The researchers concluded that because poor CD4 responders run a greater risk of serious non-AIDS diagnoses, "this fragile population" urgently needs "innovative immune therapies."
References
1. Lapadula G, Chateneaud L, Gori A, et al. Increased risk of serious non-AIDS defining events and mortality among immunological non-responders to antiretroviral therapy in the Italian MASTER cohort. XIX International AIDS Conference. July 22-27, 2012. Abstract MOPE102.
2. Torti C, Lapadula G, Maggiolo F, et al. Predictors of AIDS-defining events among advanced naive patients after HAART. HIV Clin Trials. 2007;8:112-120. http://www.mastercohort.it/PublicDocs/Lavori_Pubb_28.pdf.
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