1 / 14

CHER Trial: Early Antiretroviral Therapy and Mortality Among HIV-Infected Infants

CHER Trial: Early Antiretroviral Therapy and Mortality Among HIV-Infected Infants. New England J Med 2008;359 (21): 2233-2244. Background- Standard HIV screening & therapy. WHO recommends screening of infants with: Known maternal HIV Clinical signs & symptoms of possible HIV

ayanna
Download Presentation

CHER Trial: Early Antiretroviral Therapy and Mortality Among HIV-Infected Infants

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. CHER Trial: Early Antiretroviral Therapy and Mortality Among HIV-Infected Infants New England J Med 2008;359 (21): 2233-2244

  2. Background- Standard HIV screening & therapy • WHO recommends screening of infants with: • Known maternal HIV • Clinical signs & symptoms of possible HIV • HIV antibody test (ELISA) • Sensitive in age >18 months • Confirm all positive tests w/ PCR • If PCR not available, repeat ELISA at 18 months • HIV DNA PCR, RNA assay • Most sensitive and specific, test of choice under 18 months

  3. Background- current WHO guidelines for starting ART

  4. CHER Trial: Early antiretroviral therapy and mortality among HIV-infected infants • Phase 3, randomized, open-label trial • Clinical question: Does the early diagnosis of HIV and initiation of antiretroviral therapy in infants reduce mortality or the progression of HIV? • Primary end-points: 1) Time to death 2) Failure of first-line antiretroviral therapy

  5. Methods • Setting: • 377 infants enrolled from two HIV research centers in South Africa (Soweta & Cape Town) between Aug 2005 – Feb 2007 • Inclusion criteria: • Infants 6 – 12 weeks of age • Positive DNA PCR • RNA viral load >1000 • CD4 >25% • Exclusion criteria:

  6. Methods con’t • Study design • Phase 3, open, randomized, controlled trial • Randomly assigned to 3 treatment groups: • Early therapy group: 96 weeks • Early therapy group: 40 weeks • Deferred therapy group • Outcome measures: • Primary: • Time to death • Failure of first-line antiretroviral therapy • Failure to reach CD4 20% by 24 wks • Decrease in CD4 <20% after 24wks • Severe stage B or C events (clinical failure) • Toxicity requiring drug changes or discontinuation

  7. Validity • 1. Randomized?-yes • 2. Randomization process blinded from investigators?-yes • 3. Groups similar?-yes

  8. Validity con’t Table 1. Baseline characteristics

  9. Validity con’t • 4. Patients maintained in randomized groups? -yes, intention to treat principle • Although proportion of deferred therapy group evaluated partway through trial and started on antiretroviral therapy due to finding of difference in mortality between groups (total number not specified) • Additional 155 HIV infected infants referred from centers other than the two primary centers • 5. Blinded?-no • Patients • Clinicians • Outcome assessors

  10. Validity con’t • 6. Follow-up complete? • Non-completion • Early therapy groups: 6% • Deferred therapy group: 3% • Adherence rates • Zidovudine 87.8% • Lamivudine 90.2% • Lopinavir-ritonavir 92.1% • 7. Follow-up appropriate length? • Pts followed every 4 weeks until wk 24, every 8 wks until wk 48, every 12 weeks thereafter • Median follow up 40 weeks

  11. Results con’t • Overall mortality • Deferred therapy 16% vs. Early therapy groups 4% (relative reduction of 76%, p<0.001) • Progression of HIV • Deferred therapy 25.6% vs. Early therapy groups 6.3% (relative reduction 75%, p<0.001) • CD4 percentage • 12 wks: -7.5% Deferred group, +4.8% Early therapy (absolute difference 12.3%, p<0.001) • 24 wks: -5.6% Deferred group, +5.9% Early therapy (absolute difference 11.5%, p<0.001) • 32 wks: -4.8% Deferred group, +4.5% Early therapy (absolute difference 9.3%, p<0.001)

  12. Discussion • 1. Study limitations, questions? • 2. Clinically significant?

  13. Discussion • 3.Applicable to our patient population? • Yes • 4. Future directions?

  14. Key Points • Early HIV diagnosis and initiation of therapy at a median of 7wks reduced infant mortality by 76% and reduced HIV progression by 75% • This study advocates starting early antiretroviral therapy upon diagnosis regardless of CD4 percentage, CD4 count or clinical stage

More Related