Background: Adverse drug interactions between rifabutin (RBT) and efavirenz (EFV) have raised pharmacokinetic (PK) concerns in the treatment of HIV-infected TB patients (pts).

Methods: PK drug levels of all HIV-infected TB pts admitted to AGH, Florida, between June 2000 and September 2002 and concomitantly treated with RBT and an EFV-containing antiretroviral therapy (ART) were analyzed. The initial dose of RBT was 300 or 450 mg twice weekly and of EFV was 600 mg daily. T-cell studies, HIV viral load (VL), and isoniazid (INH) and RBT serum drug levels (2 and 6 hrs after dose) were obtained within 7 days prior to initiation of ART. Follow-up T-cell studies, HIV VL, and INH and RBT (2 and 6 hrs after dose), and EFV (peak and trough, 4 and 24 hrs after dose) serum levels were obtained 2–6 wks after initiation of ART.

Results: There were 20 pts (median age 43, male 10, race [black 16, white 1, Hispanic 3]). On admission, medians of the initial absolute CD4 count, CD4%, CD4/CD8 ratio and VL (all n = 20), were 82 (range 4–669), 8.6% (0.5–37.2), 0.18 (0.00–0.70), and 124,580 (< 400 – >750,000), respectively. The repeat absolute CD4 count, CD4%, CD4/CD8 ratio, and HIV VL (all n = 20) were 171 (range 11–1,212), 17.0% (1.6–40.4), 0.30 (0.02–0.82), and 924.5 (< 400–8,623), respectively. There was significant improvement in absolute CD4 count, percent and ratio as well as HIV VL (all p < 0.01). Six (6) of 20 pts were on 450 mg of RBT, and 14/20 were on 300 mg. Median RBT levels (2 and 6 hrs after ingestion) drawn pre-ART were 0.17 and 0.50 on 450 mg, 0.12 and 0.15 on 300 mg. Levels done 2 wks after ART were 0.16 and 0.21 (p > 0.2 and p < 0.03 compared to pre-ART, by Wilcoxon signed rank test) on 450 mg and 0.14 and 0.11 (both p > 0.2 compared to pre ART) on 300 mg (expected range 0.3–0.9 mcg/ml). Fourteen (14) of 20 pts were also on INH 900 mg twice wkly. Median 2 and 6 hrs INH levels before vs after ART were 5.44 and 0.86 vs 6.90 and 1.59 (p > 0.2 compared to preART), respectively (expected range 10–15 mcg/ml). Median EFV levels at 4 and 24 hrs were 2.99 and 1.35 (expected levels at 4 to 5 hrs and 24 hrs are 3–10 and 0.5–1.6 mcg/ml), respectively. All pts had or are in the process of successful completion of TB therapy.

Conclusion: In pts on concurrent RBT and EFV, neither RBT nor EFV serum levels were significantly affected except for lower 6 hrs RBT level after EFV initiation. Pts on RBT 300 mg did not appear to reach the expected PK range, supporting the current recommendation for RBT of 450 mg twice wkly when using an EFV-containing ART. EFV serum levels were within expected range, suggesting that the concomitant use of both agents may be effective.