Effects of TB Treatment on Virologic and CD4 Response to ART
Effects of TB Treatment on Virologic and CD4 Response to ART
Objective: To determine the impact of tuberculosis (TB) treatment at the time of combination antiretroviral therapy (cART) initiation on virologic and CD4 cell count response to cART.
Methods: Systematic review and meta-analysis of studies reporting HIV RNA and CD4 cell count response, stratified by TB treatment status at cART initiation. Stratified random-effects and meta-regression analyses were used when possible.
Results: Twenty-five eligible cohort studies reported data on 49 578 (range 42–15 646) adults, of whom 8826 (18%) were receiving TB treatment at cART initiation. Seventeen studies reported virologic response; 21 reported CD4 cell count response. The summarized random-effects relative risk (RRRE) of virologic suppression in those receiving vs. not receiving TB treatment at different time points following cART initiation was 1.06 (0.86–1.29) at 1–4 months, 0.91 (0.83–1.00) at 6 months, 0.99 (0.94–1.05) at 11–12 months, and 0.99 (0.77–1.28) at 18–48 months. The overall RRRE at 1–48 months was 0.97 (95% confidence interval 0.92–1.03). Available data regarding the effect of TB treatment on virologic failure were heterogeneous and inconclusive (13 estimates). Differences in median CD4 cell count gain between those receiving vs. not receiving TB treatment ranged from −10 to 60 cells/μl (median 27) by 6 months (seven estimates) and −10 to 29 (median 6) by 11–12 months (five estimates), although the heterogeneity of the response measures did not support meta-analysis.
Conclusion: Patients receiving TB treatment at cART initiation experience similar virologic suppression and CD4 cell count reconstitution as those not receiving TB treatment, reinforcing the need to start cART during TB treatment and allowing more confidence in clinical decision-making.
Tuberculosis (TB) threatens the health of people living with HIV (PLWH). Globally in 2011, 13% of incident TB cases were coinfected with HIV and an estimated 0.4 million TB deaths occurred among PLWH. Given the World Health Organization's 2010 recommendation that all PLWH with TB be initiated on combination antiretroviral therapy (cART), regardless of CD4 cell count, and the goal of 100% cART coverage of coinfected patients by 2015, many individuals are initiating cART while concurrently on TB therapy. PLWH who are also being treated for TB may experience a differential response to cART due to drug–drug interactions, an increased risk of drug toxicity, immune reconstitution inflammatory syndrome (IRIS), and the potential for lower adherence due to the high pill burden. The effect of TB treatment and its associated potential challenges and complications regarding a patient's response to cART require careful evaluation.
We aimed to describe the impact of receiving TB treatment at the time of cART initiation on virologic and CD4 cell count response to cART among HIV-infected adults. In addition, we highlighted the various outcome measures used in the literature and make recommendations for some methodological standards that may ease future between-study comparisons.
Abstract and Introduction
Abstract
Objective: To determine the impact of tuberculosis (TB) treatment at the time of combination antiretroviral therapy (cART) initiation on virologic and CD4 cell count response to cART.
Methods: Systematic review and meta-analysis of studies reporting HIV RNA and CD4 cell count response, stratified by TB treatment status at cART initiation. Stratified random-effects and meta-regression analyses were used when possible.
Results: Twenty-five eligible cohort studies reported data on 49 578 (range 42–15 646) adults, of whom 8826 (18%) were receiving TB treatment at cART initiation. Seventeen studies reported virologic response; 21 reported CD4 cell count response. The summarized random-effects relative risk (RRRE) of virologic suppression in those receiving vs. not receiving TB treatment at different time points following cART initiation was 1.06 (0.86–1.29) at 1–4 months, 0.91 (0.83–1.00) at 6 months, 0.99 (0.94–1.05) at 11–12 months, and 0.99 (0.77–1.28) at 18–48 months. The overall RRRE at 1–48 months was 0.97 (95% confidence interval 0.92–1.03). Available data regarding the effect of TB treatment on virologic failure were heterogeneous and inconclusive (13 estimates). Differences in median CD4 cell count gain between those receiving vs. not receiving TB treatment ranged from −10 to 60 cells/μl (median 27) by 6 months (seven estimates) and −10 to 29 (median 6) by 11–12 months (five estimates), although the heterogeneity of the response measures did not support meta-analysis.
Conclusion: Patients receiving TB treatment at cART initiation experience similar virologic suppression and CD4 cell count reconstitution as those not receiving TB treatment, reinforcing the need to start cART during TB treatment and allowing more confidence in clinical decision-making.
Introduction
Tuberculosis (TB) threatens the health of people living with HIV (PLWH). Globally in 2011, 13% of incident TB cases were coinfected with HIV and an estimated 0.4 million TB deaths occurred among PLWH. Given the World Health Organization's 2010 recommendation that all PLWH with TB be initiated on combination antiretroviral therapy (cART), regardless of CD4 cell count, and the goal of 100% cART coverage of coinfected patients by 2015, many individuals are initiating cART while concurrently on TB therapy. PLWH who are also being treated for TB may experience a differential response to cART due to drug–drug interactions, an increased risk of drug toxicity, immune reconstitution inflammatory syndrome (IRIS), and the potential for lower adherence due to the high pill burden. The effect of TB treatment and its associated potential challenges and complications regarding a patient's response to cART require careful evaluation.
We aimed to describe the impact of receiving TB treatment at the time of cART initiation on virologic and CD4 cell count response to cART among HIV-infected adults. In addition, we highlighted the various outcome measures used in the literature and make recommendations for some methodological standards that may ease future between-study comparisons.
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