Background:
Patients co-infected with HIV and M. tuberculosis (MTB) receiving treatment
with rifabutin (RFB) and other TB medications, are now treated with highly
active antiretroviral therapy (HAART). Although ritonavir (RTV) may increase
blood levels of RFB, the recommended dose of RFB 150mg given twice weekly
(2/wk) may be sub-therapeutic.
Objective:
To determine the serum RFB levels when given 150mg, 2/wk with once-daily APV
and RTV.
Methods:
Antiretroviral naïve patients, who are pan-sensitive to TB medications and
have completed 2 months of TB treatment were enrolled in the study. They
were treated with a RFB 150mg, 2/wk and INH 15mg/kg (with vitamin B6 50mg)
2/wk with once-daily doses of APV 1200 mg, RTV 200 mg, abacavir (ABC) 300
mg, and lamivudine (3TC) 300 mg as directly observed treatment. Plasma
concentrations of APV and RFB levels were measured at baseline, at 2, 4, 6
and 8 weeks of therapy. Samples were obtained at pre-dose, 2- and 4-hours
post-dose. Samples were analyzed using solid phase extraction and HPLC
(lower limit of detection 0.05 g/mL). When baseline RFB levels were below
0.1 g/mL, the dose was increased. INH/vitamin B6 were given per CDC
guidelines. Data were pooled and presented using descriptive statistics.
Results:
So far, two patients have completed the PK study. Serum RFB levels from 36
time points are presented (levels in g/mL). Data from additional time
points are being analyzed.
|
Rifabutin Doses |
150mg
2/wk |
300mg
2/wk |
450mg
2/wk |
|
|
Pre-dose |
2h |
4h |
Pre-dose |
2h |
4h |
Pre-dose |
2h |
4h |
|
Mean |
<0.05 |
<0.05 |
<0.05 |
0.06 |
0.26 |
0.55 |
<0.05 |
0.22 |
0.32 |
|
Std. Error |
0.003 |
0.01 |
0.01 |
<0.05 |
0.09 |
0.11 |
<0.05 |
<0.05 |
<0.05 |
|
Median |
<0.05 |
0.05 |
<0.05 |
0.05 |
0.28 |
0.39 |
<0.05 |
0.25 |
0.35 |
|
Count |
3 |
3 |
3 |
5 |
5 |
5 |
4 |
4 |
4 |
|
Expected Values (mg/mL): |
0.1-0.3 |
0.3-0.9 |
0.4-0.8 |
|
|
|
|
|
|
Conclusions:
Results suggest that when patients are given RFB in the presence of APV
1200mg/RTV 200mg/day, the levels of RFB are sub-therapeutic, despite
increasing the dose of RFB to 450 mg 2/wk. Consistent with other reports,
these data appear to support the anticipated change in CDC treatment
guidelines to administer RFB 3 times weekly in MTB patients receiving HAART
with RTV-boosted regimens.
Investigator' s
Addendum
July 02, 2003 -
Dr. Boulanger recommended that
the abstract be amended to state that
any of the post dose levels less
than 2 mcg/ml is considered low. |
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