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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
Presented by Kathy Wood, United States.
Lichtenstein K.1, Armon C.2, Moorman A.3, Buchacz K.3, Wood K.2, Brooks J.3, and the HOPS Investigators
1University of Colorado Health Sciences Center, Denver, CO, United States, 2Cerner Corporation, Vienna, VA, United States, 3Centers for Disease Control and Prevention, Atlanta, GA, United States
Objectives: Concerns about nucleoside analogue (NA) associated toxicities have led to initiation of antiretroviral (AR) treatment at later stages of HIV infection when levels of chronic inflammation and degree of CD4+ T cell depletion are highest. Our goal was to identify the optimal time to begin AR treatment based on the risk of developing toxicities.
Methods: We analyzed a prospective, dynamic cohort of >8000 patients followed since 1993. We stratified patients by pre-HAART CD4 cell count (pHCD4) – (0-49, 50-199, 200-349, 350-499, and >500 cells/mm3). Chi-square and multivariate Cox proportional hazards analyses were performed to assess risks for developing three toxicities: peripheral neuropathy (PN), anemia, and renal insufficiency (RI).
Results: Up to 1,969 patients were analyzed for the three outcomes. In the multivariate Cox proportional hazards analyses significant independent factors (p<0.05, adjusted hazard ratio in parentheses) associated with development of: PN included baseline age (1.4, 10 year increments), pHCD4 < 200 cells/ mm3 (1.6), stavudine use during follow-up (2.1), and didanosine use during follow-up (3.4); anemia included pHCD4 < 200 cells/ mm3 (1.8), baseline hemoglobin (0.8, continuous variable), zidovudine use during follow-up (2.0), and 14 or more drinks per week at HOPS entry (2.0); and RI included baseline age (1.5, 10 year increments), male gender (0.6), white race (0.5), creatinine clearance at baseline (0.8, continuous variable), and history of zidovudine use at baseline (2.0).
Conclusions:
• Incidence of NA-associated toxicities is significantly reduced when HAART is initiated at progressively higher CD4 counts.
• NA-associated toxicities occur shortly after initiation of ARV treatment (within 6-12 months).
• The majority of patients (>80%) do not develop these toxicities.
• If the toxicities do not develop in the first year of treatment, the risk of development of these toxicities declines with continued use of these NAs.
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