Poor initial CD4+ recovery with antiretroviral therapy prolongs immune depletion and increases risk for AIDS and non-AIDS diseases
Jason V Baker, Grace Peng, Joshua Rapkin, David Krason, Cavan Reilly, Winston P Cavert, Donald I Abrams, Rodger D MacArthur, Keith Henry, James D Neaton, Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA), Jason V Baker, Grace Peng, Joshua Rapkin, David Krason, Cavan Reilly, Winston P Cavert, Donald I Abrams, Rodger D MacArthur, Keith Henry, James D Neaton, Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA)
Abstract
Background: Low CD4+ increases risk for both AIDS- and non-AIDS-related morbidity and mortality. The magnitude of CD4+ recovery early after initial antiretroviral therapy (ART) is important in the ultimate duration of immune depletion.
Methods: We examined CD4+ recovery among 850 participants in the Community Program for Clinical Research on AIDS Flexible Initial Retrovirus Suppressive Therapies study with virologic suppression (ie, achieved an HIV RNA level <400 copies/mL) with 8 months of initial ART and determined subsequent risk for AIDS, non-AIDS diseases (non-AIDS cancers and cardiovascular, end-stage renal, and liver diseases), or death using Cox regression during a median 5-year follow-up.
Results: Mean pretreatment CD4+ was 221 cells/microL; 18% (n = 149) had a poor CD4+ recovery (<50 cells/microL) after 8 months of effective ART, resulting in lower CD4+ over 5 years. Older age (hazard ratio 1.34/10 yrs, P = 0.003) and lower screening HIV RNA (hazard ratio 0.65 per log10 copies/mL higher, P = 0.001), but not screening CD4+, were associated with a poor CD4+ recovery. After 8 months of effective ART, 30 patients experienced the composite outcome of AIDS, non-AIDS, or death among participants with a poor CD4+ recovery (rate = 5.8/100 person-years) and 74 patients among those with an adequate recovery (>or=50 cells/muL; rate = 2.7/100 person-years) (adjusted hazard ratio = 2.24, P < 0.001). The risk of this composite outcome associated with a poor CD4+ recovery declined when ART was initiated at higher CD4+ counts (P < 0.01).
Conclusions: Impaired immune recovery, despite effective ART, results in longer time spent at low CD4+, thereby increasing risk for a broad category of HIV-related morbidity and mortality conditions.
Figures
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Incidence of AIDS, non-AIDS disease,…
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Incidence of AIDS, non-AIDS disease, or death based on initial CD4+ recovery. Rate…
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Risk of AIDS, non-AIDS, or…
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Risk of AIDS, non-AIDS, or death stratified by pretreatment CD4+ count. The risk…
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- Research Support, N.I.H., Extramural
- Acquired Immunodeficiency Syndrome / immunology
- Acquired Immunodeficiency Syndrome / mortality
- Acquired Immunodeficiency Syndrome / physiopathology*
- Acquired Immunodeficiency Syndrome / virology
- Anti-HIV Agents / therapeutic use*
- Antiretroviral Therapy, Highly Active
- CD4 Lymphocyte Count*
- CD4-Positive T-Lymphocytes / virology*
- Disease Progression
- Follow-Up Studies
- HIV / physiology
- HIV Infections / drug therapy*
- HIV Infections / immunology
- HIV Infections / physiopathology
- HIV Infections / virology
- Humans
- Proportional Hazards Models
- RNA, Viral / analysis
- Risk Factors
- Anti-HIV Agents
- RNA, Viral
- Full Text Sources
- Medical
- Research Materials
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Source: PubMed