Factors Associated with Reduced Antituberculous Serum Drug Concentrations in Patients with HIV-TB Coinfection

Abstract

We describe correlates of reduced antituberculous serum drug concentrations (SDCs) in HIV-infected patients receiving treatment for active tuberculosis (TB). Cross-sectional analysis of individuals diagnosed with HIV and active TB in Northern Alberta, Canada, was performed. Of the 30 HIV-TB cases, 27 underwent measurement of SDCs. Rates of low SDCs were 9 of 26 (34%) for isoniazid (INH) and 16 of 25 (64%) for rifamycins. Increased weight and elevated body mass index (BMI) correlated with low SDCs for rifampin (P < .05) and increased weight also correlated with reduced SDCs for INH (P < .05). This suggests that conventional antituberculous dosing may be too low and consideration should be given to increase the maximum initial weight-based doses in HIV-infected patients.

A Review of Moxifloxacin for the Treatment of Drug‐Susceptible Tuberculosis

“…Of note, most of the PK data from studies including moxifloxacin in tuberculosis treatment regimens were in HIV‐uninfected individuals and in populations outside of Africa. Although HIV coinfection itself may lead to altered PK and lower concentrations of tuberculosis drugs, little data exists on the potential interactions of moxifloxacin with antiretroviral treatment. One recent study reported a 42% increase in oral clearance of moxifloxacin, resulting in a 30% decrease in moxifloxacin AUC when coadministered with efavirenz‐based antiretroviral treatment in patients with HIV coinfection .…”

Interaction of obesity and infections

“…Seventy‐three studies examined the response to infection treatment in the obese vs. normal‐weight populations (Supporting Information http://onlinelibrary.wiley.com/doi/10.1111/obr.12320/suppinfo) . Fifteen of the studies did not find a statistically significant difference between the two groups.…”

“…Additionally, although hypothesized that eradication of parasites, which contribute to stunted growth, may lead to obesity, no such evidence is currently observed (182). Fifty-three of the 73 studies reported either a reduced or no response to treatment in obese individuals (75,(112)(113)(114)(115)(116)118,120,122,123,(125)(126)(127)(128)132,139,142,143,147,148,150,156,157,160,162,168,(170)(171)(172)(173)(174)(175)179,180). Failure to attain or sustain adequate serum or tissue drug levels in individuals of higher BMI appears to be the most common underlying explanation.…”

The Use of Therapeutic Drug Monitoring in Complex Antituberculous and Antiretroviral Drug Dosing in HIV/Tuberculosis-Coinfected Patients

“…Given the frequency of reduced antituberculous SDCs reported in the literature, the standard rifampin 600 mg dose and isoniazid 300 mg dose may be suboptimal and weight-based dosing of 10 and 5 mg/kg/d, respectively, should be considered. 8 Based on TDM, it has been suggested that the median doses required to achieve therapeutic concentrations in an HIV/TB cohort were isoniazid 600 mg/d (range, 300-1500 mg/d), rifampin 1050 mg/d (range, 600-1200 mg/d), and rifabutin 300 mg (range, 150-450 mg 3 times/week). 1 Although limited literature exists regarding the safety of higher antituberculous dosing, no patients experienced adverse effects secondary to these higher drug doses in this study.…”

“…In our previously described cohort of patients coinfected with HIV/TB who had completed antituberculous TDM, 20 (74%) of the 27 patients had a low SDC for at least 1 drug and underwent subsequent dose modification. 8 These 2 cases were selected as they provide an illustration of low SDCs and/or delayed absorption of antituberculous drugs. As shown in case 1, rifampin 900 mg daily and isoniazid 450 mg daily were required to achieve therapeutic SDCs.…”