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

In 2012, an estimated 1.1 million (14%) of the 8.6 million patients diagnosed with active tuberculosis (TB) disease worldwide were also infected with human immunodeficiency virus (HIV) (1). Although, under current World Health Organization (WHO) guidelines, all people diagnosed with TB and HIV are eligible for antiretroviral therapy (ART), only 57% initiated ART during TB treatment in 2012 (1). Findings from randomized controlled trials demonstrated that early ART, defined as within 2–4 weeks of start of TB treatment, reduces mortality in patients with a CD4 count of 50 cells/mm3 (2–4). On the basis of these findings, the WHO recommends ART initiation within 2 weeks of TB treatment for patients with a CD4 count of <50 cells/mm3 and within 8 weeks for all people diagnosed with HIV and TB (5). Findings from randomized controlled trials are not always replicable in less strictly controlled settings. Observational studies from sub-Saharan Africa have found that most patients initiate ART late, after 8 weeks of TB treatment (6–10). Lack of integration of TB and HIV treatment services has been identified as one of the key contributors to this delay (9, 10). Interventions to integrate TB and HIV services have been shown to reduce, but not eliminate, delay in ART initiation (11, 12). Implementation fidelity, defined as the degree to which an intervention is implemented as intended, is a potential modifier of the relationship between an intervention and its intended outcome and is important to translation of evidence-based recommendations into clinical practice (13, 14). Achieving high implementation fidelity can help to replicate the success an intervention has achieved in randomized controlled trials (13). The relatively low coverage of timely ART initiation in patients with TB suggests that implementation fidelity to the 2012 WHO guidelines for timing of ART initiation in TB patients may be a challenge in routine clinical settings, even with integrated HIV/TB treatment. Data on implementation fidelity in resource-limited settings and its impact on desired outcomes are limited. We aimed to quantify the impact of implementation fidelity to CD4-stratified timing of ART initiation for TB patients on mortality in a prospective cohort of patients receiving integrated TB/HIV treatment at the primary care level in Kinshasa, Democratic Republic of the Congo.