Abstract
BackgroundUnderstanding the immune response to combination antiretroviral therapy (cART) is essential for a clear approach to tuberculosis (TB) preventive therapy. We investigated the immunological recovery in cART-treated HIV-infected patients developing TB compared to those who remained free of TB.MethodsWe extracted data of HIV-infected patients from a multicenter cohort for the HIV clinical surveillance in Germany. No patients included in our study had TB at the beginning of the observation. Using a longitudinal mixed model, we assessed the differences in the mean change of biomarkers (CD4+ cell count, CD8+ cell count, CD4:CD8 ratio and viral load) since cART initiation in patients who remained free of TB vs. those developing TB. To detect the best-fit trajectories of the immunological biomarkers, we applied a multivariable fractional polynomials model.ResultsWe analyzed a total of 10,671 HIV-infected patients including 139 patients who developed TB during follow-up. The highest TB incidences were observed during the first two years since cART initiation (0.32 and 0.50 per 100 person-years). In an adjusted multivariable mixed model, we found that the average change in CD4+ cell count recovery was significantly greater by 33 cells/μl in patients who remained free of TB compared with those developing TB. After the initial three months of cART, 65.6% of patients who remaining free of TB achieved CD4+ count of ≥400 cells/μl, while only 11.3% of patients developing TB reached this immunological status after the three months of cART. We found no differences in the average change of CD8+ cell count, CD4:CD8 ratio or viral load between the two-patient groups.ConclusionAll HIV-infected patients responded to cART. However, patients developing TB showed reduced recovery in CD4+ cell count and this might partly explain the incident TB in HIV-infected patients receiving cART. These findings reinforce the importance of adjunctive TB preventive therapy for patients with reduced recovery in CD4+ cell count.
Highlights
Understanding the immune response to combination antiretroviral therapy is essential for a clear approach to tuberculosis (TB) preventive therapy
CART is associated with a dramatic decline in TB risk by 70%-90% among HIV-infected patients [5], TB incidence remains elevated in settings with high [5, 6] and low TB incidence [5, 7]
We aimed to investigate whether the average change in immunological biomarkers is associated with TB development and to analyze the immunological dynamic in combination antiretroviral therapy (cART)-treated HIV-infected patients in relation to development of active TB
Summary
Understanding the immune response to combination antiretroviral therapy (cART) is essential for a clear approach to tuberculosis (TB) preventive therapy. We investigated the immunological recovery in cART-treated HIV-infected patients developing TB compared to those who remained free of TB. Infection with HIV is the most potent risk factor for tuberculosis (TB) [1]. CART is associated with a dramatic decline in TB risk by 70%-90% among HIV-infected patients [5], TB incidence remains elevated in settings with high [5, 6] and low TB incidence [5, 7]. HIV infection was associated with lower TB treatment success rates even in settings with available cART [9, 10]
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