Suboptimal Exposure to Anti‐TB Drugs in a TBM/HIV+ Population Is Not Related to Antiretroviral Therapy
A placebo‐controlled trial that compares the outcomes of immediate vs. deferred initiation of antiretroviral therapy in HIV +ve tuberculous meningitis (TBM) patients was conducted in Vietnam in 2011. Here, the pharmacokinetics of rifampicin, isoniazid, pyrazinamide, and ethambutol were investigated...
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| Veröffentlicht in: | Clinical pharmacology and therapeutics 2018-03, Vol.103 (3), p.449-457 |
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| container_title | Clinical pharmacology and therapeutics |
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| creator | Török, ME Aljayyoussi, G Waterhouse, D Chau, TTH Mai, NTH Phu, NH Hien, TT Hope, W Farrar, JJ Ward, SA |
| description | A placebo‐controlled trial that compares the outcomes of immediate vs. deferred initiation of antiretroviral therapy in HIV +ve tuberculous meningitis (TBM) patients was conducted in Vietnam in 2011. Here, the pharmacokinetics of rifampicin, isoniazid, pyrazinamide, and ethambutol were investigated in the presence and absence of anti‐HIV treatment in 85 patients. Pharmacokinetic analyses show that HIV therapy has no significant impact on the pharmacokinetics of TB drugs in this cohort. The same population, however, displayed generally low cerebrospinal fluid (CSF) and systemic exposures to rifampicin compared to previously reported HIV –ve cohorts. Elevated CSF concentrations of pyrazinamide, on the other hand, were strongly and independently correlated with increased mortality and neurological toxicity. The findings suggest that the current standard dosing regimens may put the patient at risk of treatment failure from suboptimal rifampicin exposure, and potentially increasing the risk of adverse central nervous system events that are independently correlated with pyrazinamide CSF exposure. |
| doi_str_mv | 10.1002/cpt.646 |
| format | Article |
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Here, the pharmacokinetics of rifampicin, isoniazid, pyrazinamide, and ethambutol were investigated in the presence and absence of anti‐HIV treatment in 85 patients. Pharmacokinetic analyses show that HIV therapy has no significant impact on the pharmacokinetics of TB drugs in this cohort. The same population, however, displayed generally low cerebrospinal fluid (CSF) and systemic exposures to rifampicin compared to previously reported HIV –ve cohorts. Elevated CSF concentrations of pyrazinamide, on the other hand, were strongly and independently correlated with increased mortality and neurological toxicity. 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The findings suggest that the current standard dosing regimens may put the patient at risk of treatment failure from suboptimal rifampicin exposure, and potentially increasing the risk of adverse central nervous system events that are independently correlated with pyrazinamide CSF exposure.</description><subject>Adult</subject><subject>Aged</subject><subject>Antiretroviral Therapy, Highly Active - adverse effects</subject><subject>Antitubercular Agents - pharmacokinetics</subject><subject>Antitubercular Agents - therapeutic use</subject><subject>Coinfection</subject><subject>Double-Blind Method</subject><subject>Drug Interactions</subject><subject>Female</subject><subject>HIV Seropositivity - complications</subject><subject>HIV Seropositivity - mortality</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Neurotoxicity Syndromes - epidemiology</subject><subject>Neurotoxicity Syndromes - metabolism</subject><subject>Survival Analysis</subject><subject>Treatment Failure</subject><subject>Tuberculosis, Meningeal - complications</subject><subject>Tuberculosis, Meningeal - drug therapy</subject><subject>Tuberculosis, Meningeal - mortality</subject><issn>0009-9236</issn><issn>1532-6535</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kNFOwjAUhhujEUTjG5jeeUEGbbd26yUgCgkq0ent0o4zmRl06TaVOx_BZ_RJLEG88-rPn3znT86H0DklPUoI66dl3ROBOEBtyn3mCe7zQ9QmhEhPMl-00ElVvboayCg6Ri0WUUFYyNpo-dhoU9b5ShV4_FGaqrGAa4MH6zr__vyKh_jKNi8VztdY4Xh4259Mn7t4bsqmUHVu1nha4TtT4wdwHRb7Uwu1NW-5davxEqwqN6foKFNFBWe_2UFP1-N4NPFm9zfT0WDmpUxw4UEqlVABRAJ0mkmmaQiLjHHNs1BEAfiSU52qTAtfEhoFIZdUMdAKfOEi8jvocrebWlNVFrKktO47u0koSbauEucqca4cebEjy0avYPHH7eU4oLsD3vMCNv_tJKN5vJ37AY9pc5g</recordid><startdate>201803</startdate><enddate>201803</enddate><creator>Török, ME</creator><creator>Aljayyoussi, G</creator><creator>Waterhouse, D</creator><creator>Chau, TTH</creator><creator>Mai, NTH</creator><creator>Phu, NH</creator><creator>Hien, TT</creator><creator>Hope, W</creator><creator>Farrar, JJ</creator><creator>Ward, SA</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>201803</creationdate><title>Suboptimal Exposure to Anti‐TB Drugs in a TBM/HIV+ Population Is Not Related to Antiretroviral Therapy</title><author>Török, ME ; Aljayyoussi, G ; Waterhouse, D ; Chau, TTH ; Mai, NTH ; Phu, NH ; Hien, TT ; Hope, W ; Farrar, JJ ; Ward, SA</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2656-ec9a6a4e86ebcf92b17edf25b5f7684e3951bcafb63901847591a2ebae362eb83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Antiretroviral Therapy, Highly Active - adverse effects</topic><topic>Antitubercular Agents - pharmacokinetics</topic><topic>Antitubercular Agents - therapeutic use</topic><topic>Coinfection</topic><topic>Double-Blind Method</topic><topic>Drug Interactions</topic><topic>Female</topic><topic>HIV Seropositivity - complications</topic><topic>HIV Seropositivity - mortality</topic><topic>Humans</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Neurotoxicity Syndromes - epidemiology</topic><topic>Neurotoxicity Syndromes - metabolism</topic><topic>Survival Analysis</topic><topic>Treatment Failure</topic><topic>Tuberculosis, Meningeal - complications</topic><topic>Tuberculosis, Meningeal - drug therapy</topic><topic>Tuberculosis, Meningeal - mortality</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Török, ME</creatorcontrib><creatorcontrib>Aljayyoussi, G</creatorcontrib><creatorcontrib>Waterhouse, D</creatorcontrib><creatorcontrib>Chau, TTH</creatorcontrib><creatorcontrib>Mai, NTH</creatorcontrib><creatorcontrib>Phu, NH</creatorcontrib><creatorcontrib>Hien, TT</creatorcontrib><creatorcontrib>Hope, W</creatorcontrib><creatorcontrib>Farrar, JJ</creatorcontrib><creatorcontrib>Ward, SA</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>Clinical pharmacology and therapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Török, ME</au><au>Aljayyoussi, G</au><au>Waterhouse, D</au><au>Chau, TTH</au><au>Mai, NTH</au><au>Phu, NH</au><au>Hien, TT</au><au>Hope, W</au><au>Farrar, JJ</au><au>Ward, SA</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Suboptimal Exposure to Anti‐TB Drugs in a TBM/HIV+ Population Is Not Related to Antiretroviral Therapy</atitle><jtitle>Clinical pharmacology and therapeutics</jtitle><addtitle>Clin Pharmacol Ther</addtitle><date>2018-03</date><risdate>2018</risdate><volume>103</volume><issue>3</issue><spage>449</spage><epage>457</epage><pages>449-457</pages><issn>0009-9236</issn><eissn>1532-6535</eissn><abstract>A placebo‐controlled trial that compares the outcomes of immediate vs. deferred initiation of antiretroviral therapy in HIV +ve tuberculous meningitis (TBM) patients was conducted in Vietnam in 2011. Here, the pharmacokinetics of rifampicin, isoniazid, pyrazinamide, and ethambutol were investigated in the presence and absence of anti‐HIV treatment in 85 patients. Pharmacokinetic analyses show that HIV therapy has no significant impact on the pharmacokinetics of TB drugs in this cohort. The same population, however, displayed generally low cerebrospinal fluid (CSF) and systemic exposures to rifampicin compared to previously reported HIV –ve cohorts. Elevated CSF concentrations of pyrazinamide, on the other hand, were strongly and independently correlated with increased mortality and neurological toxicity. 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| subjects | Adult Aged Antiretroviral Therapy, Highly Active - adverse effects Antitubercular Agents - pharmacokinetics Antitubercular Agents - therapeutic use Coinfection Double-Blind Method Drug Interactions Female HIV Seropositivity - complications HIV Seropositivity - mortality Humans Male Middle Aged Neurotoxicity Syndromes - epidemiology Neurotoxicity Syndromes - metabolism Survival Analysis Treatment Failure Tuberculosis, Meningeal - complications Tuberculosis, Meningeal - drug therapy Tuberculosis, Meningeal - mortality |
| title | Suboptimal Exposure to Anti‐TB Drugs in a TBM/HIV+ Population Is Not Related to Antiretroviral Therapy |
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