Drug Malabsorption and Resistant Tuberculosis in HIV-Infected Patients

Abstract

1 despite a 21-year search for a diagnosis, the patient's illness remains hazy. The diagnosis is most obviously hereditary coproporphyria. The patient and her brother were both affected.The patient had a 21-year history of recurrent abdominal pain, with neither clinical nor surgical peritonitis and in the absence of remarkable sequelae. There was evidence of autonomic disturbances: a rapid pulse, an episode of urinary retention, and decreased peristalsis with dilated loops on a plain film of the abdomen. There was also evidence of neuropsychiatric phenomena: anxiety, myalgia, and an episode of transient hemianopia, a form of focal seizure, and a postictal headache, which was misinterpreted as a conversion reaction. There was a history of intolerance of amitriptyline, isoniazid, and rifampin, which are considered unsafe in patients with porphyria. The coincidental findings of dry cough and splenomegaly probably amount to a red herring and did not contribute to the patient's illness.Several quantitative tests of spot urine samples from the patient revealed a threefold to fivefold elevation in the level of porphobilinogen, and her brother had a value that was at the upper limit of the normal range. Coproporphyrin III excretion in feces and coproporphyrinogen oxidase in leukocytes and cultured skin fibroblasts were not assayed. The erythrocyte porphobilinogen deaminase activity was normal, as one would have predicted, since it is characteristically normal in patients with hereditary coproporphyria. 2 M ARWAN S. A KASHEH , M.D. Amman, Jordan P.O. Box 9668 Instructions for Letters to the Editor Letters to the Editor are considered for publication (subject to editing and abridgment), provided they are submitted in duplicate, are typewritten and triple-spaced, and do not exceed 400 words of text, a maximum of five references, and one figure or table. Letters should have no more than three authors, and all should sign the letter. Please include a word count, your telephone number, and your fax number (if available).Letters should not duplicate similar material being submitted or published elsewhere, and they should not contain abbreviations. Financial associations or other possible conflicts of interest should always be disclosed. Submission of a letter constitutes permission for the Massachusetts Medical Society, its licensees, and its assignees to use it in the Journal 's various editions (print, data base, and optical disk), in anthologies, revisions, and any other form or medium.Letters referring to a recent Journal article must be received within four weeks of the article's publication. To expedite receipt of such letters, we encourage authors outside the United States to communicate by fax (617-739-9864 or 617-734-4457).We are unable to provide prepublication proofs, and unpublished material will not be returned to authors unless a stamped, self-addressed envelope is enclosed. Receipt of letters is not acknowledged, but correspondents will be notified when a decision is made.

Suboptimal Exposure to Anti‐TB Drugs in a TBM/HIV+ Population Is Not Related to Antiretroviral Therapy

“…The reasons behind the low RIF exposure in this cohort are unknown, and whether HIV status is the driving force behind the low exposure has been a subject of debate as previously discussed in the introduction. Other reasons might include wasting or malnutirtion and associated issues such as oedema in the small intestines, or bacterial over growth which have been reasons that were suggested in the past 33,34 .…”

Population Pharmacokinetics of Rifampin in Pulmonary Tuberculosis Patients, Including a Semimechanistic Model To Describe Variable Absorption

“…Several potential causes for this variability may be immediately discounted. No food intake was allowed until 2 h postdose, eliminating food effects as a possible source (46,73), and no significant correlation was found with HIV coinfection (11,16,17,47,49,58,64). Other sources of this variability might be attributed to the fact that the studies were conducted during clinical treatment in a hospital setting.…”

Reduced Antituberculosis Drug Concentrations in HIV-Infected Patients Who Are Men or Have Low Weight: Implications for International Dosing Guidelines

“…Reduced drug exposure among HIV-infected patients (13,19) may contribute to the worse treatment outcomes reported among patients with HIV-associated tuberculosis than for HIV-uninfected patients, notably when less robust antituberculosis regimens are used, treatment duration is 6 months or less, or intermittent dosing is employed (14,16,23,31). There is concern that the greater risk of tuberculosis recurrence among HIVinfected patients with more advanced immune suppression (4,24,37) may, in part, be due to lower drug concentrations (26,28,33).…”