Is Starting Antiretroviral Therapy (ART) in HIV Positive Adults with CD4 Cell Count of <300 Cells/μl within Four Weeks of Initiating New Tuberculosis (TB) Therapy More Effective in Reducing Mortality Rates than Starting ART Four Weeks or Later after Initiating New TB Therapy?
Date of Award
Selective Evidence-Based Medicine Review
Master of Science in Health Sciences - Physician Assistant
John Cavenagh, PhD, PA-C
OBJECTIVE: The objective of this selective EBM review is to determine whether or not starting antiretroviral therapy (ART) in HIV positive adults with CD4 cell count of /µl within four weeks of initiating new tuberculosis therapy more effective in reducing mortality rates than starting ART four weeks or later after initiating new tuberculosis therapy.
STUDY DESIGN: Systematic review of three English language primary studies published in the New England Journal of Medicine in 2011.
DATA SOURCES: Three open label, randomized, controlled trials published in 2011, comparing the timing of ART for HIV+ adults with confirmed or suspected new TB infections to reduce mortality rates in reference to initiating TB therapy were obtained using PubMed, Medline and OVID databases.
OUTCOME MEASURED: Outcomes measured include mortality rate, new AIDS defining illness, and immune reconstitution inflammatory syndrome (IRIS).
RESULTS: Karim et. al. (2011) found in patients with a CD4+ cell count less than 300 cells/µl the incidence rate of death was 7.0% in the earlier ART group compared to 6.9% in the later ART group, with IRIS occurring in 20.0% in the early ART and 8.4% in the late ART group. In groups with CD4+ cell counts of less than 50 cells/µl the mortality rates were 8.1% and 20.0% and incidence rates of IRIS as 37.8% and 11.4% for early and late ART respectively. Blanc et. al. (2011) found in patients with CD4+ cell counts of 200 or less cells/µl a 17.8% mortality rate in the early ART group compared to a 27.4% mortality rate in the late ART group. They also found a significant increase in IRIS in the early ART group, 42.5% compared to just 20.0%. Havlir et. al. (2011) found a 7.7% mortality
rate in the early ART group and 9.2% in the late ART group with both groups starting with a CD4+ count of less than 200 cells/µl. For patients with CD4+ T-cell count of less than 50 cells/µl, they found the mortality rate and incidence of new AIDS-defining illnesses was significantly lower in the early ART group 15.5% vs. 26.6% in the later group.
CONCLUSIONS: Karim et al. and Havlir et al. both found that starting ART early in TB therapy showed no significant statistical difference in mortality outcomes in patient with a CD4+ cell count less than 300 cells/µl, but if the group has a CD4+ count of less than 50 cells/µl, new AIDS related illness and death were reduced. Blanc et al. found that survival improved when ART was initiated within 2 weeks of starting TB therapy in HIV + adults with a CD4+ count of 200 or less cells/µl. All three studies showed an increase incidence of IRIS when ART was started within four weeks of initiating TB therapy.
Erlien, Janna, "Is Starting Antiretroviral Therapy (ART) in HIV Positive Adults with CD4 Cell Count of <300 Cells>/μl within Four Weeks of Initiating New Tuberculosis (TB) Therapy More Effective in Reducing Mortality Rates than Starting ART Four Weeks or Later after Initiating New TB Therapy?" (2013). PCOM Physician Assistant Studies Student Scholarship. 123.