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Multicenter Study
. 2017 Jul 25;17(1):517.
doi: 10.1186/s12879-017-2627-y.

Immunological recovery in tuberculosis/HIV co-infected patients on antiretroviral therapy: implication for tuberculosis preventive therapy

Basel Karo  1   2 , Gérard Krause  3   4 , Stefanie Castell  3 , Christian Kollan  5 , Osamah Hamouda  5 , Walter Haas  5 ; ClinSurv HIV Study Group
Collaborators, Affiliations
Multicenter Study

Immunological recovery in tuberculosis/HIV co-infected patients on antiretroviral therapy: implication for tuberculosis preventive therapy

Basel Karo et al. BMC Infect Dis. .

Abstract

Background: 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.

Methods: We 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.

Results: We 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.

Conclusion: All 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.

Keywords: Antiretroviral therapy; Developed country; HIV/aids; Immune recovery; Tuberculosis.

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Conflict of interest statement

Ethics approval and consent to participate

The ClinSurv HIV study protocol was approved by the German Federal Commissioner for Data Protection and Freedom of Information. No separate ethical approval or additional permission is required for secondary analysis of the study data due to the anonymous nature of the data.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Tuberculosis incidence among HIV-infected patients since cART initiation in the German ClinSurv HIV cohort, 1999-2013. TB cases diagnosed within the first three months of cART initiation were excluded. cART: combination antiretroviral therapy
Fig. 2
Fig. 2
Change in biomarkers since cART initiation among HIV-infected patients in the ClinSurv HIV cohort, 1999-2013. (a) Change in CD4+ cell count. (b) Change in CD8+ cell count. (c) Change in CD4:CD8 ratio. (d) Change in viral load
Fig. 3
Fig. 3
Immunological recovery since cART initiation among HIV-infected patients in the German ClinSurv HIV Cohort, 1999-2013. (a) Profile plot of CD4+ cell count. (b) Profile plot of CD8+ cell count. (c) Profile plot of CD4:CD8 ratio. (d) Profile plot of viral load. The best-fitting model of CD4+ cells count is FP2 (0, 0.5) for subjects who remained free of TB and is FP2 (−1,1) for subjects who developed TB. Irrespective to TB development, the best-fitting model of CD8+ cells count is FP2 (−0.5, −0.5)], of CD4:CD8 ratio is FP2 (−0.5, −0.5), and of viral load is FP2 (−2, −0.5). No measurements were included after TB diagnosis. TB: tuberculosis; FP2: second-degree fractional polynomial model
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