Dataset Information

Early antituberculosis drug exposure in hospitalized patients with human immunodeficiency virus-associated tuberculosis.

ABSTRACT:

Aims

Patients hospitalized at the time of human immunodeficiency virus-associated tuberculosis (HIV-TB) diagnosis have high early mortality. We hypothesized that compared to outpatients, there would be lower anti-TB drug exposure in hospitalized HIV-TB patients, and amongst hospitalized patients exposure would be lower in patients who die or have high lactate (a sepsis marker).

Methods

We performed pharmacokinetic sampling in hospitalized HIV-TB patients and outpatients. Plasma rifampicin, isoniazid and pyrazinamide concentrations were measured in samples collected predose and at 1, 2.5, 4, 6 and 8 hours on the third day of standard anti-TB therapy. Twelve-week mortality was ascertained for inpatients. Noncompartmental pharmacokinetic analysis was performed.

Results

Pharmacokinetic data were collected in 59 hospitalized HIV-TB patients and 48 outpatients. Inpatient 12-week mortality was 11/59 (19%). Rifampicin, isoniazid and pyrazinamide exposure was similar between hospitalized and outpatients (maximum concentration [C_max ]: 7.4 vs 8.3 ?g mL^-1 , P = .223; 3.6 vs 3.5 ?g mL^-1 , P = .569; 50.1 vs 46.8 ?g mL^-1 , P = .081; area under the concentration-time curve from 0 to 8 hours: 41.0 vs 43.8 mg h L^-1 , P = 0.290; 13.5 vs 12.4 mg h L^-1 , P = .630; 316.5 vs 292.2 mg h L^-1 , P = .164, respectively) and not lower in inpatients who died. Rifampicin and isoniazid C_max were below recommended ranges in 61% and 39% of inpatients and 44% and 35% of outpatients. Rifampicin exposure was higher in patients with lactate >2.2 mmol L^-1 .

Conclusion

Mortality in hospitalized HIV-TB patients was high. Early anti-TB drug exposure was similar to outpatients and not lower in inpatients who died. Rifampicin and isoniazid C_max were suboptimal in 61% and 39% of inpatients and rifampicin exposure was higher in patients with high lactate. Treatment strategies need to be optimized to improve survival.

SUBMITTER: Schutz C

PROVIDER: S-EPMC7163385 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Publications

Early antituberculosis drug exposure in hospitalized patients with human immunodeficiency virus-associated tuberculosis.

Schutz Charlotte C Chirehwa Maxwell M Barr David D Ward Amy A Janssen Saskia S Burton Rosie R Wilkinson Robert J RJ Shey Muki M Wiesner Lubbe L Denti Paolo P McIlleron Helen H Maartens Gary G Meintjes Graeme G

British journal of clinical pharmacology 20200217 5

<h4>Aims</h4>Patients hospitalized at the time of human immunodeficiency virus-associated tuberculosis (HIV-TB) diagnosis have high early mortality. We hypothesized that compared to outpatients, there would be lower anti-TB drug exposure in hospitalized HIV-TB patients, and amongst hospitalized patients exposure would be lower in patients who die or have high lactate (a sepsis marker).<h4>Methods</h4>We performed pharmacokinetic sampling in hospitalized HIV-TB patients and outpatients. Plasma ri ...[more]

PMID: 31912537

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Project description:IntroductionThe association of human immunodeficiency virus (HIV) infection with Burkitt lymphoma is related to the presence of Epstein Barr virus infection and the impact of the HIV antigen on the expansion of B-polyclonal cells. In Southeast Europe, the association is rare, and recognizing this is important in the therapeutic decision to increase patient survival rate. The association of HIV with Burkitt lymphoma and tuberculosis is even more rarely described in the literature.Patient concernsWe present the case of a 40-year-old patient who presented with a 3-week history of fever (max. 38.7 °C), painful axillary swelling on the right side, lumbar pain, gait disorders, headache, and night sweats. Clinical manifestations included marked weight loss (about 30 kg in the last 2 months before his admission).DiagnosisA LyCD4 count of 38/μL and a HIV1 viral load of 384,000/mm3, classified the patient into a C3 stage. A biopsy of the right axillary lymph node was performed for suspected ganglionic tuberculosis due to immunodeficiency. Histopathological examination confirmed the diagnosis of Burkitt lymphoma. Cultures on Löwenstein-Jensen medium from sputum harvested at first admission were positive for Mycobacterium tuberculosis.InterventionsHighly active antiretroviral therapy, chemotherapeutic agents for Burkitt lymphoma, anti-tuberculous drug therapy, neurosurgical intervention of spinal cord decompression, and antibiotic therapy of the associated bacterial infection.OutcomeBurkitt lymphoma disseminated rapidly, with central nervous system, spinal cord, osteomuscular, adrenal, and spleen involvement. The evolution under treatment was unfavorable, with patient death occurring 6 months after diagnosis.ConclusionsThe association of HIV infection with Burkitt lymphoma and tuberculosis is rare in the highly active antiretroviral therapy (HAART) era, posing prompt and multidisciplinary therapeutic management issues. Similar cases of HIV-TB and Burkitt lymphoma association have been described, but none of the other cases showed the involvement of the central nervous system or of the bilateral adrenal glands.

Project description:BackgroundThe risk of individuals infected with human immunodeficiency virus (HIV)-1 developing tuberculosis (TB) is high, while both prognostic and diagnostic tools remain insensitive. The potential for plasma biomarkers to predict which HIV-1-infected individuals are likely to progress to active disease is unknown.MethodsThirteen analytes were measured from QuantiFERON Gold in-tube (QFT) plasma samples in 421 HIV-1-infected persons recruited within the screening and enrollment phases of a randomized, controlled trial of isoniazid preventive therapy. Blood for QFT was obtained pre-randomization. Individuals were classified into prevalent TB, incident TB, and control groups. Comparisons between groups, supervised learning methods, and weighted correlation network analyses were applied utilizing the unstimulated and background-corrected plasma analyte concentrations.ResultsUnstimulated samples showed higher analyte concentrations in the prevalent and incident TB groups compared to the control group. The largest differences were seen for C-X-C motif chemokine 10 (CXCL10), interleukin-2 (IL-2), IL-1?, transforming growth factor-? (TGF-?). A predictive model analysis using unstimulated analytes discriminated best between the control and prevalent TB groups (area under the curve [AUC] = 0.9), reasonably well between the incident and prevalent TB groups (AUC > 0.8), and poorly between the control and incident TB groups. Unstimulated IL-2 and IFN-? were ranked at or near the top for all comparisons, except the comparison between the control vs incident TB groups. Models using background-adjusted values performed poorly.ConclusionsSingle plasma biomarkers are unlikely to distinguish between disease states in HIV-1 co-infected individuals, and combinations of biomarkers are required. The ability to detect prevalent TB is potentially important, as no blood test hitherto has been suggested as having the utility to detect prevalent TB amongst HIV-1 co-infected persons.

Dataset Information

Early antituberculosis drug exposure in hospitalized patients with human immunodeficiency virus-associated tuberculosis.

Aims

Methods

Results

Conclusion

Publications

Early antituberculosis drug exposure in hospitalized patients with human immunodeficiency virus-associated tuberculosis.

Similar Datasets

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