Poor initial CD4+ recovery with antiretroviral therapy prolongs immune depletion and increases risk for AIDS and non-AIDS diseases.
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.
Baker
Jason V
JV
Department of Biostatistics, University of Minnesota, Minneapolis, MN, USA. baker459@umn.edu
Peng
Grace
G
Rapkin
Joshua
J
Krason
David
D
Reilly
Cavan
C
Cavert
Winston P
WP
Abrams
Donald I
DI
MacArthur
Rodger D
RD
Henry
Keith
K
Neaton
James D
JD
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000401:mortality / Q000503:physiopathology* / Q000821:virology; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D018450:Disease Progression; D005500:Follow-Up Studies; D006678:HIV / Q000502:physiology; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology / Q000821:virology; D006801:Humans; D016016:Proportional Hazards Models; D012367:RNA, Viral / Q000032:analysis; D012307:Risk Factors
D019380:Anti-HIV Agents; D012367:RNA, Viral