The Pharmacokinetics and Safety of IDV/r With NRTIs in HIV/TB Co-infected Patients Receiving Rifampicin

Study Overview
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Brief Summary
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We believe that there is a strong rationale for the study of IDV/r 600/100 bid as a boosted-PI combination that, in the presence of RMP, is able to produce a satisfactory PK profile associated with adequate antiretroviral potency, tolerability and efficacy.

Detailed Description
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The fixed-dose combination of d4T+3TC+NVP (GPOvir) has been widely used in Thailand since June 2002. The prevalence of NNRTI resistance has increased since 2005. Efavirenz-based antiretroviral therapy (ART) is preferred in patients with TB/HIV receiving rifampin-containing TB regimens. However, efavirenz cannot be used in the context of NNRTI failure, intolerance or toxicity. The optimal ART in populations receiving rifampicin remains unknown. Rifabutin, which is recommended in combination with a boosted protease inhibitor (PI/r) is expensive and not available in Thailand and other developing countries. Ritonavir-boosted indinavir (IDV/r) is potent and the cheapest boosted PI available in Thailand. If IDV/r in combination with rifampin demonstrates suitable pharmacokinetics and is well tolerated, this regimen might prove useful and could be widely implemented. However, high rates of gastrointestinal and renal toxicity have been demonstrated in Thai patients receiving standard doses of IDV/r 800/100 BID. We believe that there is a strong rationale to study if IDV/r 600/100 BID in combination with rifampin is able to produce a satisfactory pharmacokinetic profile, with antiretroviral potency, tolerability and efficacy.

Official Title
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The Pharmacokinetics and Safety of Ritonavir-boosted Indinavir 600/100mg Bid Combined With NRTIs in ARV naïve HIV/TB Co-infected Patients Receiving Rifampicin Containing Anti-tuberculosis Therapy

Conditions
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HIV Infections, Tuberculosis

Intervention / Treatment
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* Drug: indinavir/ritonavir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed HIV positive after voluntary counselling and testing Aged between 18 and 60 years of age Antiretroviral treatment naive CD4+ cell count of <200 cells/mm3 at the time of TB diagnosis ALT <5 times ULN Serum creatinine <1.4 mg/dl Haemoglobin >8 mg/L TB diagnosis; either probable (clinical symptoms plus chest x-ray and response to anti-TB medication) or definitive( sputum AFB culture confirmed) and receiving or planning to receive rifampicin-containing anti-TB therapy for at least a 2 week period before the initiation of ART No other active OI (CDC class C event) Able to provide written informed consent Exclusion Criteria: Current use of steroids and other immunosuppressive agents Current use of any prohibited medications related to compliance and drug pharmacokinetics Patients with current alcohol or illicit substance use that in the opinion of the site Principal Investigator would conflict with any aspect of the conduct of the trial. Previous exposure to nevirapine monotherapy Unlikely to be able to remain in follow-up for the protocol defined period Patients with proven or suspected acute hepatitis. Patients with chronic viral hepatitis are eligible provided ALT, AST < 5 x ULN. Karnofsky performance score <30%

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: 1<br>IDV/r 600/100 mg + rifampicin | Drug: indinavir/ritonavir<br>* IDV/r 600/100 mg BID + rifampicin OD for at least 2 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pharmacokinetics of ritonavir-boosted indinavir 600/100mg bid in combination with rifampicin-containing anti-TB therapy. |  | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety of ritonavir-boosted indinavir 600/100mg bid in combination with rifampicin-containing anti-TB therapy |  | 48 weeks | 
| efficacy of ritonavir-boosted indinavir 600/100mg bid in combination with rifampicin-containing anti-TB therapy |  | 48 weeks | 
| the prevalence of immune recovery syndrome of TB and other HIV-related conditions after ritonavir-boosted indinavir 600/100mg bid |  | 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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indinavir/ritonavir, HIV/TB, rifampicin, PK and efficacy of IDV/RTV 600/100 mg BID with rifampicin, Treatment Naive