A Study of CD4-Stratified Timing of Antiretroviral Therapy Among Patients Receiving Integrated Tuberculosis and HIV Treatment in a Highly Resource-Limited Setting

In 2012, the World Health Organization recommended that HIV-infected patients starting tuberculosis (TB) treatment be initiated on antiretroviral therapy (ART) after 8 weeks if CD4 count greater than or equal to 50 cells/mm3 and after 2 weeks if CD4 count <50 cells/mm3. Examination of this type of CD4-stratified ART timing strategy would be useful to inform development and implementation of this new recommendation. In the Integration of TB and AntiRetroviral Treatment study, nurses implemented a CD4-stratified timing strategy for ART initiation among HIV-infected patients starting TB treatment in Kinshasa, Democratic Republic of Congo. Participants were eligible for ART initiation at 1 month if CD4 count <100 cells/mm3 or WHO clinical stage 4 for reason other than extrapulmonary TB, at 2 months if CD4 count 100-350 cells/mm3, or at completion of TB treatment if subsequently CD4 count <100 cells/mm3 or WHO clinical stage 4. We compared expected and observed timing of ART initiation and used logistic regression with backward stepwise elimination to determine predictors of delayed ART initiation, defined as deviation from strategy. Subsequently, we used the parametric g-formula to estimate the difference in 6-month mortality risk in the population with observed fidelity to CD4-stratified ART timing and in the population complete (100%) fidelity to CD4-stratifeid ART timing. Of 492 adult participants, 235 (47.8%) experienced delayed ART initiation. Contraindication to any ARV drug (adjOR 2.91, 95% CI 1.22-6.95), lower baseline CD4 count (adjOR 1.20, 95% CI 1.08-1.33 per 100 cells/mm3), TB drug intolerance (adjOR 1.93, 95% CI 1.23-3.02), and non-disclosure of HIV-infection (adjOR 1.50, 95% CI 1.03-2.18) predicted delayed ART initiation. In the subset of 395 patients eligible at 1 or 2 months, mortality risk was 12.0% with observed fidelity and 7.8% with complete fidelity, corresponding to a risk difference of -4.2% (95% CI: -8.1, -0.3, %) and preventable fraction of mortality of 35.1% (95% CI: 2.9-67.9%). Timing of ART initiation per CD4-stratified strategy in all patients may be a challenge to achieve in highly-resource settings; however, would be worthwhile to further reduce mortality among HIV-infected patients with TB. Pragmatic approaches to ensure timely ART initiation in those identified at-risk of delayed ART initiation are needed.