Efavirenz pharmacokinetics and pharmacodynamics in HIV-infected persons receiving rifapentine and isoniazid for tuberculosis prevention

Citation: Podany AT, Bao Y, Swindells S, Chaisson RE, Andersen JW, Mwelase T, Supparatpinyo K, Mohapi L, Gupta A, Benson Cam, Kim P, Fletcher CV on behalf of the ACTG A5279 Study Team. Efavirenz pharmacokinetics and pharmacodynamics in HIV-infected persons receiving rifapentine and efavirenz-pharmacokinetics-and-pharmacodynamics-in-hiv-infected-person. Clin Infect Dis. 2015 Oct 15;61(8):1322-7. doi: 10.1093/cid/civ464. Epub 2015 Jun 16. PMID: 26082504. PMCID: PMC4583578.

Access full article:

http://www.ncbi.nlm.nih.gov/pubmed/26082504

BACKGROUND:

Concomitant use of rifamycins to treat or prevent tuberculosis can result in subtherapeutic concentrations of antiretroviral drugs. We studied the interaction of efavirenz with daily rifapentine and isoniazid in human immunodeficiency virus (HIV)-infected individuals receiving a 4-week regimen to prevent tuberculosis.

METHODS:

Participants receiving daily rifapentine and isoniazid with efavirenz had pharmacokinetic evaluations at baseline and weeks 2 and 4 of concomitant therapy. Efavirenz apparent oral clearance was estimated and the geometric mean ratio (GMR) of values before and during rifapentine and isoniazid was calculated. HIV type 1 (HIV-1) RNA was measured at baseline and week 8.

RESULTS:

Eighty-seven participants were evaluable: 54% were female, and the median age was 35 years (interquartile range [IQR], 29-44 years). Numbers of participants with efavirenz concentrations ≥1 mg/L were 85 (98%) at week 0; 81 (93%) at week 2; 78 (90%) at week 4; and 75 (86%) at weeks 2 and 4. Median efavirenz apparent oral clearance was 9.3 L/hour (IQR, 6.42-13.22 L/hour) at baseline and 9.8 L/hour (IQR, 7.04-15.59 L/hour) during rifapentine/isoniazid treatment (GMR, 1.04 [90% confidence interval, .97-1.13]). Seventy-nine of 85 (93%) participants had undetectable HIV-1 RNA (<40 copies/mL) at entry; 71 of 75 (95%) participants had undetectable HIV-1 RNA at week 8. Two participants with undetectable HIV-1 RNA at study entry were detectable (43 and 47 copies/mL) at week 8.

CONCLUSIONS:

The proportion of participants with midinterval efavirenz concentrations ≥1 mg/L did not cross below the prespecified threshold of >80%, and virologic suppression was maintained. Four weeks of daily rifapentine plus isoniazid can be coadministered with efavirenz without clinically meaningful reductions in efavirenz mid-dosing concentrations or virologic suppression.

Clin Infect Dis. 2015 Jun 16. pii: civ464. [Epub ahead of print]

Categories

CRS
Topics

Clinical Trials

A5253: Sensitivity and Specificity of Mycobacterium...

An estimated 3 million HIV-infected individuals will enter programs for antiretroviral (ARV) treatment in the coming year, with...

Read More

A5320: Viral Hepatitis C Infection Long-term Cohort Study...

A5320/V-HICS is an observational, prospective, long-term follow-up study in hepatitis C virus (HCV) monoinfected and HCV/HIV-1...

Read More

NWCS 414, Evaluation of a Serum Biosignature for Identifying...

We will address our hypothesis using a case-control study design. We plan to leverage the existing biorepository of...

Read More

A5324: A Randomized, Double-Blinded, Placebo-Controlled...

ACTG A5324 is a phase IV randomized, double-blinded, placebo-controlled study to assess the efficacy of adding Maraviroc (MVC)...

Read More

IMPAACT 2034 - Phase I Study of the Pharmacokinetics,...

This is a Phase I, multi-site, open-label, non-comparative study of the PK, safety, tolerability, and acceptability of a...

Read More