Rates of Disease Progression by Baseline CD4 Cell Count and Viral Load After Initiating Triple-Drug Therapy

TLDR

HIV treatment guidelines use CD4 counts and viral load, yet the prognostic value of these markers after starting triple‑drug therapy remains incompletely defined. This study aimed to quantify rates of death and AIDS or death among patients initiating triple‑drug antiretroviral therapy, stratified by baseline CD4 count and HIV RNA level. A population‑based cohort of 1,219 antiretroviral‑naïve adults in British Columbia who began therapy between 1996 and 1999 was followed through September 2000, with cumulative mortality calculated at various CD4 and viral load thresholds. Overall mortality was low (6.7% AIDS‑related deaths, 2.9% cumulative mortality at 12 months), and multivariate analysis showed that patients with CD4 < 50 /µL or 50–199 /µL had 6.7‑fold and 3.4‑fold higher risk of death than those with CD4 ≥ 200 /µL, while age and sex had no effect; thus progression clustered in those with CD4 < 200 /µL.

Abstract

ContextCurrent recommendations for initiation of antiretroviral therapy in patients infected with human immunodeficiency virus type 1 (HIV) are based on CD4 T-lymphocyte cell counts and plasma HIV RNA levels. The relative prognostic value of each marker following initiation of therapy has not been fully characterized.ObjectiveTo describe rates of disease progression to death and AIDS or death among patients starting triple-drug antiretroviral therapy, stratified by baseline CD4 cell count and HIV RNA levels.Design, Setting, and ParticipantsPopulation-based analysis of 1219 antiretroviral therapy–naive HIV-positive men and women aged 18 years or older in British Columbia who initiated triple-drug therapy between August 1, 1996, and September 30, 1999.Main Outcome MeasureCumulative mortality rates from the initiation of triple-drug antiretroviral therapy to September 30, 2000, determined using various CD4 cell and plasma HIV RNA thresholds.ResultsAs of September 30, 2000, 82 patients had died of AIDS-related causes, for a crude AIDS-related mortality rate of 6.7%. The product limit estimate (SE) of the cumulative mortality rate at 12 months was 2.9% (0.5%). In univariate analyses, a prior diagnosis of acquired immunodeficiency syndrome (AIDS), CD4 cell count, use of protease inhibitors, and HIV RNA level were associated with mortality. There was no difference in mortality by age or sex. Only CD4 cell count remained statistically significant in the multivariate analysis. After controlling for AIDS, protease inhibitor use, and plasma HIV RNA level at baseline, patients with CD4 cell counts of less than 50/µL were 6.67 (95% confidence interval [CI], 3.61-12.34) times and those with counts of 50/µL to 199/µL were 3.41 (95% CI, 1.93-6.03) times more likely to die than those with counts of at least 200/µL.ConclusionOur data demonstrate uniformly low rates of disease progression to death and AIDS or death among patients starting antiretroviral therapy with CD4 cell counts of at least 200/µL. In our study, disease progression to death and AIDS or death was clustered among patients starting therapy with CD4 cell counts less than 200/µL.