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 David MacArthur, Keith Henry, James D. Neaton

Research output: Contribution to journalArticle

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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/μL; 18% (n = 149) had a poor CD4+ recovery (<50 cells/μL) 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 (≥50 cells/μL; 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.

Original languageEnglish (US)
Pages (from-to)541-546
Number of pages6
JournalJournal of Acquired Immune Deficiency Syndromes
Volume48
Issue number5
DOIs
StatePublished - Aug 15 2008

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Acquired Immunodeficiency Syndrome
HIV
Therapeutics
RNA
Morbidity
End Stage Liver Disease
Mortality
Retroviridae
CD4 Lymphocyte Count
Chronic Kidney Failure
Research
Neoplasms

Keywords

  • AIDS
  • Antiretroviral therapy
  • CD4 recovery
  • Cardiovascular disease
  • HIV disease progression
  • Immune reconstitution
  • Kidney disease
  • Liver disease
  • Non-AIDS conditions
  • Non-AIDS-defining malignancies

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

Cite this

Poor initial CD4+ recovery with antiretroviral therapy prolongs immune depletion and increases risk for AIDS and non-AIDS diseases. / Baker, Jason V.; Peng, Grace; Rapkin, Joshua; Krason, David; Reilly, Cavan; Cavert, Winston P.; Abrams, Donald I.; MacArthur, Rodger David; Henry, Keith; Neaton, James D.

In: Journal of Acquired Immune Deficiency Syndromes, Vol. 48, No. 5, 15.08.2008, p. 541-546.

Research output: Contribution to journalArticle

Baker, Jason V. ; Peng, Grace ; Rapkin, Joshua ; Krason, David ; Reilly, Cavan ; Cavert, Winston P. ; Abrams, Donald I. ; MacArthur, Rodger David ; Henry, Keith ; Neaton, James D. / Poor initial CD4+ recovery with antiretroviral therapy prolongs immune depletion and increases risk for AIDS and non-AIDS diseases. In: Journal of Acquired Immune Deficiency Syndromes. 2008 ; Vol. 48, No. 5. pp. 541-546.
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T1 - Poor initial CD4+ recovery with antiretroviral therapy prolongs immune depletion and increases risk for AIDS and non-AIDS diseases

AU - Baker, Jason V.

AU - Peng, Grace

AU - Rapkin, Joshua

AU - Krason, David

AU - Reilly, Cavan

AU - Cavert, Winston P.

AU - Abrams, Donald I.

AU - MacArthur, Rodger David

AU - Henry, Keith

AU - Neaton, James D.

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N2 - 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/μL; 18% (n = 149) had a poor CD4+ recovery (<50 cells/μL) 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 (≥50 cells/μL; 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.

AB - 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/μL; 18% (n = 149) had a poor CD4+ recovery (<50 cells/μL) 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 (≥50 cells/μL; 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.

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KW - Cardiovascular disease

KW - HIV disease progression

KW - Immune reconstitution

KW - Kidney disease

KW - Liver disease

KW - Non-AIDS conditions

KW - Non-AIDS-defining malignancies

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