RESEARCH PAPER
Anti-tuberculosis drug concentrations and treatment outcomes among HIV-infected patients with tuberculosis
Submission date: 2017-03-05
Final revision date: 2018-02-10
Acceptance date: 2018-02-12
Publication date: 2018-05-21
HIV & AIDS Review 2018;17(2):111-116
KEYWORDS
TOPICS
ABSTRACT
Introduction:
A poor response to tuberculosis (TB) treatment in patients with human immunodeficiency virus (HIV) infection can be related to inadequate adherence or low anti-tuberculosis drug concentrations in serum. Therapeutic drug monitoring (TDM) may be a useful tool to optimize drug therapy in these patients. This study aimed to determine serum concentrations of anti-TB drugs and treatment outcomes in HIV/TB patients.
Material and methods:
Twenty-two HIV/TB infected patients were entered into the study. Venous blood was obtained 2 h after a daily dose of isoniazid (INH), rifampin (RIF), and pyrazinamide (PZA). Serum levels of anti-TB drugs were analyzed using high pressure liquid chromatography (HPLC) and compared with published normal ranges. Treatment outcomes were assessed according to World Health Organization (WHO) definitions.
Results:
All the patients (median age: 35 years [range 27-57 years], median CD4+: 16 cells/mm3 [range 5-444 cells/mm3]) had low or very low serum concentrations of INH and RIF. Serum concentration of PZA was in the reference (normal) range in 5 (22.73%) patients. Of 22 patients, 4 were considered cured, 10 died on TB treatment or during follow-up, 5 relapsed after treatment, and 3 were lost to follow-up.
Conclusions:
Low serum concentrations of anti-TB drugs and poor treatment outcomes are common among our patients. Further studies in a wider patient sample are required to explore the association between anti-TB drug concentrations and treatment outcomes.
A poor response to tuberculosis (TB) treatment in patients with human immunodeficiency virus (HIV) infection can be related to inadequate adherence or low anti-tuberculosis drug concentrations in serum. Therapeutic drug monitoring (TDM) may be a useful tool to optimize drug therapy in these patients. This study aimed to determine serum concentrations of anti-TB drugs and treatment outcomes in HIV/TB patients.
Material and methods:
Twenty-two HIV/TB infected patients were entered into the study. Venous blood was obtained 2 h after a daily dose of isoniazid (INH), rifampin (RIF), and pyrazinamide (PZA). Serum levels of anti-TB drugs were analyzed using high pressure liquid chromatography (HPLC) and compared with published normal ranges. Treatment outcomes were assessed according to World Health Organization (WHO) definitions.
Results:
All the patients (median age: 35 years [range 27-57 years], median CD4+: 16 cells/mm3 [range 5-444 cells/mm3]) had low or very low serum concentrations of INH and RIF. Serum concentration of PZA was in the reference (normal) range in 5 (22.73%) patients. Of 22 patients, 4 were considered cured, 10 died on TB treatment or during follow-up, 5 relapsed after treatment, and 3 were lost to follow-up.
Conclusions:
Low serum concentrations of anti-TB drugs and poor treatment outcomes are common among our patients. Further studies in a wider patient sample are required to explore the association between anti-TB drug concentrations and treatment outcomes.
REFERENCES (31)
1.
CDC. Managing Drug Interactions in the Treatment of HIV-Related Tuberculosis. Available at: http://www.cdc.gov/tb/TB_HIV_D... (Accessed: 30 October 2014).
2.
Getahun H, Gunneberg C, Granich R, Nunn P. HIV infection associated tuberculosis: the epidemiology and the response. Clin Infect Dis 2010; 50 Suppl 3: S201-207.
3.
McIlleron H, Meintjes G, Burman WJ. Maartens G. Complications of antiretroviral therapy in patients with tuberculosis: drug interactions, toxicity, and immune reconstitution inflammatory syndrome. J Infect Dis 2007: 196 Suppl 1: S63-75.
4.
Holland DP, Hamilton CD, Weintrob AC, et al. Therapeutic drug monitoring of antimycobacterial drugs in patients with both tuberculosis and advanced human immunodeficiency virus infection. Pharmacotherapy 2009; 29: 503-510.
5.
Gurumurthy P, Ramachandran G, Hemanth Kumar AK, et al. Decreased bioavailability of rifampin and other antituberculosis drugs in patients with advanced human immunodeficiency virus disease. Antimicrob Agents Chemother 2004; 48: 4473-4475.
6.
Taylor B, Smith PJ. Dose AIDS impair the absorption of antituberculosis agents? Int J Tuberc Lung Dis 1998; 2: 670-675.
7.
Gurumurthy P, Ramachandran G, Hemanth Kumar AK, Rajasekaran S. Malabsorption of Rifampin and Isoniazid in HIV-Infected Patients With and Without Tuberculosis. Clin Infect Dis 2004; 38: 280-283.
8.
Burhan E, Ruesen C, Ruslami R, et al. Isoniazid, rifampin, and pyrazinamide plasma concentrations in relation to treatment response in Indonesian pulmonary tuberculosis patients. Antimicrob Agents Chemother 2013; 57: 3614-3619.
9.
Babalik A, Babalik A, Mannix S, et al. Therapeutic drug monitoring in the treatment of active tuberculosis. Can Respir J 2011; 18: 225-229.
10.
Um SW, Lee SW, Kwon SY, et al. Low serum concentrations of anti-tuberculosis drugs and determinants of their serum levels. Int J Tuberc Lung Dis 2007; 11: 972-978.
11.
Heysell SK, Moore JL, Keller SJ, Houpt ER. Therapeutic drug monitoring for slow response to tuberculosis treatment in a state control program, Virginia, USA. Emerg Infect Dis 2010; 6: 1546-1553.
12.
Park JS, Lee JY, Lee YJ, et al. Serum Levels of Antituberculosis Drugs and Their Effect on Tuberculosis Treatment Outcome. Antimicrob Agents Chemother 2015; 60: 92-98.
13.
World Health Organization Tuberculosis Unit, Division of Communicable Disease: Guidelines for Tuberculosis Treatment in Adults and Children in National Treatment Programmes. World Health Organization, Geneva 1991.
14.
Definitions and reporting framework for tuberculosis – 2013 revision. World Health Organization, Geneva 2013 (WHO/HTM/TB/2013.2).
15.
Peloquin CA. Using therapeutic drug monitoring to dose the antimycobacterial drugs. Clin Chest Med 1997; 18: 79-87.
16.
Kimerling ME, Phillips P, Patterson P, et al. Low serum antimycobacterial drug levels in non-HIV-infected tuberculosis patients. Chest 1998; 113: 1178-1183.
17.
Ray J, Gardiner I, Marriott D. Managing antituberculosis drug therapy by therapeutic drug monitoring of rifampicin and isoniazid. Intern Med J 2003; 33: 229-234.
18.
Weiner M, Benator D, Burman W, et al. Tuberculosis Trials Consortium, Association between acquired rifamycin resistance and the pharmacokinetics of rifabutin and isoniazid among patients with HIV and tuberculosis. Clin Infect Dis 2005; 40: 1481-1491.
19.
Weiner M, Burman W, Vernon A, et al. Tuberculosis Trials Consortium, Low isoniazid concentrations and outcome of tuberculosis treatment with once-weekly isoniazid and rifapentine. Am J Respir Crit Care Med 2003; 167: 1341-1347.
20.
Mehta JB, Shantaveerapa H, Byrd RP Jr, et al. Utility of rifampin blood levels in the treatment and follow-up of active pulmonary tuberculosis in patients who were slow to respond to routine directly observed therapy. Chest 2001; 120: 1520-1524.
21.
Morehead RS. Delayed death from pulmonary tuberculosis: unsuspected subtherapeutic drug levels. South Med J 2000; 93: 507-510.
22.
Gilljam M, Berning SE, Peloquin CA, et al. Therapeutic drug monitoring in patients with cystic fibrosis and mycobacterial disease. Eur Respir J 1999; 14: 347-351.
23.
Padmapriyadarsini C, Narendran G, Swaminathan S. Diagnosis & treatment of tuberculosis in HIV co-infected patients. Indian J Med Res 2011; 134: 850-865.
24.
Fahimi F, Kobarfard F, Tabarsi P, et al. Isoniazid blood levels in patients with pulmonary tuberculosis at a tuberculosis referral center. Chemotherapy 2011; 57: 7-11.
25.
Peloquin CA. Pharmacology of the antimycobacterial drugs. Med Clin North Am 1993; 77: 1253-1262.
26.
Narita M, Hisada M, Thimmappa B, et al. Tuberculosis recurrence: multivariate analysis of serum levels of tuberculosis drugs, human immunodeficiency virus status, and other risk factors. Clin Infect Dis 2001; 32: 515-517.
27.
McIlleron H, Wash P, Burger A, et al. Determinants of rifampin, isoniazid, pyrazinamide, and ethambutol pharmacokinetics in a cohort of tuberculosis patients. Antimicrob Agents Chemother 2006; 50: 1170-1177.
28.
Sahai J, Gallicano K, Swick L, et al. Reduced plasma concentrations of antituberculosis drugs in patients with HIV infection. Ann Intern Med 1997; 127: 289-293.
29.
Tappero JW, Bradford WZ, Agerton TB, et al. Serum concentrations of antimycobacterial drugs in patients with pulmonary tuberculosis in Botswana. Clin Infect Dis 2005; 41: 461-469.
30.
van Crevel R, Alisjahbana B, de Lange WC, et al. Low plasma concentrations of rifampicin in tuberculosis patients in Indonesia. Int J Tuberc Lung Dis 2002; 6: 497-502.
31.
Verhagen LM, López D, Hermans PW, et al. Pharmacokinetics of anti-tuberculosis drugs in Venezuelan children younger than 16 years of age: supportive evidence for the implementation of revised WHO dosing recommendations. Trop Med Int Health 2012; 17: 1449-1456.
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