The Impact of Implementation Fidelity on Mortality Under a CD4-Stratified Timing Strategy for Antiretroviral Therapy in Patients With Tuberculosis

• Published in: American journal of epidemiology Vol. 181; no. 9; pp. 714 - 722
• Main Authors: Patel, Monita R, Westreich, Daniel, Yotebieng, Marcel, Nana, Mbonze, Eron, Joseph J, Behets, Frieda, Van Rie, Annelies
• Format: Journal Article
• Language: English
• Published: United States Oxford Publishing Limited (England) 01.05.2015; Oxford University Press
• Subjects: Adult; Anti-Retroviral Agents - administration & dosage; Antiretroviral drugs; CD4 Lymphocyte Count; Confidence intervals; Democratic Republic of the Congo - epidemiology; Female; Guideline Adherence - statistics & numerical data; HIV Infections - complications; HIV Infections - drug therapy; HIV Infections - immunology; HIV Infections - mortality; Humans; Impact analysis; Male; Middle Aged; Mortality; Original Contributions; Patients; Primary Health Care - statistics & numerical data; Prospective Studies; Tuberculosis; Tuberculosis - complications; Democratic Republic of the Congo; Congo-Democratic Republic of Congo; human immunodeficiency virus; antiretroviral therapy; causal inference; implementation fidelity; HIV; parametric g-formula; tuberculosis
• ISSN: 0002-9262; 1476-6256
• DOI: 10.1093/aje/kwu338

Among patients with tuberculosis and human immunodeficiency virus type 1, CD4-stratified initiation of antiretroviral therapy (ART) is recommended, with earlier ART in those with low CD4 counts. However, the impact of implementation fidelity to this recommendation is unknown. We examined a prospective cohort study of 395 adult patients diagnosed with tuberculosis and human immunodeficiency virus between August 2007 and November 2009 in Kinshasa, Democratic Republic of the Congo. ART was to be initiated after 1 month of tuberculosis treatment at a CD4 count of <100 cells/mm(3) or World Health Organization stage 4 (other than extrapulmonary tuberculosis) and after 2 months of tuberculosis treatment at a CD4 count of 100-350 cells/mm(3). We used the parametric g-formula to estimate the impact of implementation fidelity on 6-month mortality. Observed implementation fidelity was low (46%); 54% of patients either experienced delays in ART initiation or did not initiate ART, which could be avoided under perfect implementation fidelity. The observed mortality risk was 12.0% (95% confidence interval (CI): 8.2, 15.7); under complete (counterfactual) implementation fidelity, the mortality risk was 7.8% (95% CI: 2.4, 12.3), corresponding to a risk reduction of 4.2% (95% CI: 0.3, 8.1) and a preventable fraction of 35.1% (95% CI: 2.9, 67.9). Strategies to achieve high implementation fidelity to CD4-stratified ART timing are needed to maximize survival benefit.