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

The HIV Netherlands Australia Thailand Research Collaboration

Status and phase

Completed

Phase 2

Phase 1

Conditions

Tuberculosis

HIV Infections

Treatments

Drug: indinavir/ritonavir

Study type

Interventional

Funder types

Other

Identifiers

NCT00411996

HIV-NAT 044

Details and patient eligibility

About

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.

Full description

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.

Enrollment

20 patients

Sex

All

Ages

18 to 60 years old

Volunteers

No Healthy Volunteers

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%