Active Tuberculosis Is Associated with Worse Clinical Outcomes in HIV-Infected African Patients on Antiretroviral Therapy

<div><h3>Objective</h3><p>This cohort study utilized data from a large HIV treatment program in western Kenya to describe the impact of active tuberculosis (TB) on clinical outcomes among African patients on antiretroviral therapy (ART).</p> <h3>Design</h3><p>We included all patients initiating ART between March 2004 and November 2007. Clinical (signs and symptoms), radiological (chest radiographs) and laboratory (mycobacterial smears, culture and tissue histology) criteria were used to record the diagnosis of TB disease in the program’s electronic medical record system.</p> <h3>Methods</h3><p>We assessed the impact of TB disease on mortality, loss to follow-up (LTFU) and incident AIDS-defining events (ADEs) through Cox models and CD4 cell and weight response to ART by non-linear mixed models.</p> <h3>Results</h3><p>We studied 21,242 patients initiating ART–5,186 (24%) with TB; 62% female; median age 37 years. There were proportionately more men in the active TB (46%) than in the non-TB (35%) group. Adjusting for baseline HIV-disease severity, TB patients were more likely to die (hazard ratio – HR = 1.32, 95% CI 1.18–1.47) or have incident ADEs (HR = 1.31, 95% CI: 1.19–1.45). They had lower median CD4 cell counts (77 versus 109), weight (52.5 versus 55.0 kg) and higher ADE risk at baseline (CD4-adjusted odds ratio = 1.55, 95% CI: 1.31–1.85). ART adherence was similarly good in both groups. Adjusting for gender and baseline CD4 cell count, TB patients experienced virtually identical rise in CD4 counts after ART initiation as those without. However, the overall CD4 count at one year was lower among patients with TB (251 versus 269 cells/µl).</p> <h3>Conclusions</h3><p>Clinically detected TB disease is associated with greater mortality and morbidity despite salutary response to ART. Data suggest that identifying HIV patients co-infected with TB earlier in the HIV-disease trajectory may not fully address TB-related morbidity and mortality.</p> </div

Kaplan-Meier curve of mortality (left) and new AIDS Defining Events (right) in the TB group (dashed line) versus the non-TB group (solid line).

<p>Kaplan-Meier curve of mortality (left) and new AIDS Defining Events (right) in the TB group (dashed line) versus the non-TB group (solid line).</p

Results from the piece-wise linear model for CD4 response after ART initiation.

1<p>Confidence intervals were derived based on the delta method of approximation, using estimates of the variance of the parameters produced by the GEE model. Note that the overall differences in CD4 counts present in the TB versus non-TB groups, are not evident among the three CD4 groupings suggesting that differences in CD4 response are a function of higher rates of baseline immunosuppression among TB patients rather than an independent TB-associated effect.</p

Baseline social, demographic and clinical characteristics of patients on ART in an ambulatory HIV care program in western Kenya, by TB status.

1<p>Difference between proportions (categorical variables) or means (continuous variables) of TB versus non-TB group.</p>2<p>Difference in the proportion of subjects with CD4<50 cells/ml in the TB versus the non-TB group.</p>3<p>Patients presenting with an AIDS-defining event (other than extra-pulmonary TB) 3 months prior and 2 months after ART initiation (some CD4 data are missing).</p

Estimated hazard ratios for death, Loss To Follow-Up, incident AIDS Defining Event (ADE) and first-line ART failure for patients with TB/HIV initiating ART compared to non-TB co-infected patients.

1<p>Adjusted according to CD4 count at ART initiation.</p>2<p>Including extra-pulmonary TB.</p>3<p>Surrogate marker for 1^st Line ART Failure.</p