TB treatment associated with loss of virologic suppression on ART

Temporal association between incident tuberculosis and poor virological outcomes in a South African antiretroviral treatment service.  

Gupta-Wright A, Wood R, Bekker LG, Lawn SD. J Acquir Immune Defic Syndr. 2013 Nov 1;64(3):261-70. doi: 10.1097/QAI.0b013e3182a23e9a.

Introduction: The temporal relationship between incident tuberculosis (TB) and virological outcomes during antiretroviral therapy (ART) is poorly defined. This was studied in a cohort in Cape Town, South Africa.

Methods: Data regarding TB diagnoses, ART regimens, and 4-monthly updated viral load (VL) and CD4 count measurements were extracted from a prospectively maintained database. Rates of virological breakthrough (VL > 1 000 copies/mL) and failure (VL > 1 000 copies/mL on serial measurements) following initial VL suppression were calculated. Poisson models were used to calculate incidence rate ratios (IRRs) and identify risk factors for these virological outcomes.

Results: Incident TB was diagnosed in 391 (28.5%) of 1 370 patients during a median of 5.2 years follow-up. Five hundred seventy-eight episodes of virological breakthrough and 231 episodes of virological failure occurred, giving rates of 10.0 episodes per 100 person-years and 4.0 episodes per 100 person-years, respectively. In multivariate analyses adjusted for baseline and time-updated risk factors, TB was an independent risk factor for adverse virological outcomes. These associations were strongly time dependent; the 6-month period following diagnosis of incident TB was associated with a substantially increased risk of virological breakthrough (IRR: 2.3, 95% confidence interval: 1.7 to 3.2) and failure (IRR: 2.6, 95% confidence interval: 1.6 to 4.3) compared with time without a TB diagnosis. Person-time preceding TB diagnosis or more than 6 months after a TB diagnosis was not associated with poor virological outcomes.

Conclusion: Incident TB during ART was strongly associated with poor virological outcomes during the 6-month period following TB diagnosis. Although underlying mechanisms remain to be defined, patients with incident TB may benefit from virological monitoring and treatment adherence support.

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Editor’s notes: Concurrent treatment with antiretroviral therapy (ART) and anti-tuberculous treatment presents multiple challenges for patients. These challenges include increased pill burden, increased risk of adverse effects, potential for drug-drug interactions and, if services are not integrated, the need to attend separate services for TB and HIV care. In this observational study among people taking ART in a Cape Town clinic, viral load monitoring was routinely performed every four months. The study only included patients who achieved initial virologic suppression; most were taking efavirenz-based ART. Loss of virologic suppression was more common among patients --- whose most recent CD4 count was low, with the longest duration of time on ART, and who were within 6 months of starting TB treatment.  The reason for this was not clear but possible explanations include poorer adherence to treatment when the pill burden is higher, adverse effects, or drug-drug interactions. If similar results are found elsewhere, it will be important to understand the reasons, so that appropriate interventions can be implemented. Virologic monitoring may be more important among people taking TB treatment concurrently with ART.

Avoid TB deaths
Africa
South Africa
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