Clinical trial NCT01138202: Pharmacokinetics (PK) and Safety of 2 Different Doses of Lopinavir/Ritonavir in in HIV/Tuberculosis (TB) Co-infected Patients Receiving Rifampicin Containing Anti-tuberculosis Therapy
Official title: A Pilot Study of the Pharmacokinetics and Safety of Lopinavir/Ritonavir 400/100mg Bid Versus Lopinavir/Ritonavir 600/150 mg BID Combined With Nucleoside Analogue Reverse Transcriptase Inhibitors in HIV/TB Co-infected Patients Receiving Rifampicin Containing Anti-tuberculosis Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Tuberculosis
Keywords: pharmacokinetics
safety
efficacy
Lopinavir/ritonavir
HIV/TB
rifampicin containing anti-tuberculosis therapy
Pharmacokinetics and safety of Lopinavir/ritonavir with rifampicin containing anti-tuberculosis therapy
Lead sponsor: The HIV Netherlands Australia Thailand Research Collaboration
Sponsor class: OTHER
Collaborators: name: Ministry of Health, Thailand
First posted: 2010-06-07
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: OTHER

Brief summary: To assess safety, efficacy and impact of Lopinavir/ritonavir 400/100mg bid or Lopinavir/ritonavir 600/150mg bid in combination with rifampicin-containing anti-TB therapy.

Detailed description: Fixed dose combination of d4T+3TC+NVP (GPOvir) is widely used in Thai HIV infected since June 2002. The prevalence of NNRTI resistance has increased since 2005. Tuberculosis can develop following NNRTI-based regimen failure or after introduction of a new salvage regimen with a boosted PI (immune recovery syndrome). Although, Efavirenz based HAART is preferred in TB/HIV with rifampicin containing antituberculosis. However, Efavirenz could not be used in case of NNRTI failure, intolerance or toxicity. It remains unknown how to optimally treat HIV /TB in populations in which rifampicin has to be used. Moreover, Rifabutin which is recommended when use concomitant with boosted PI4, 5, is not feasible in Thailand and other developing countries due to cost, toxicity and dosing considerations. If ritonavir-boosted LPV demonstrates suitable pharmacokinetics, and is well tolerated, this regimen might prove extremely useful and could be widely implemented. LPV/r is potent and widely available boosted PI in National Health System in Thailand. We therefore believe that there is a strong rationale and impetus for the study of LPV/r 400/100 mg bid versus LPV/r 600/150 mg 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 .

Eligibility criteria: Inclusion Criteria:

1. Confirmed HIV positive after voluntary counseling and testing
2. Aged \>18-60years of age
3. ARV naïve and NNRTI failure ( PI naive)
4. CD4+ cell count of \<350 cells/mm3 at the time of diagnosed TB
5. ALT \<5 times ULN
6. Serum creatinine \<1.4 mg/dl
7. Hemoglobin \>8 mg/L
8. TB is diagnosed and planned to receive stable doses of rifampicin-containing anti-TB therapy for at least a 2 week period after initiation of ART
9. No other active OI (CDC class C event), except oral candidiasis or disseminated MAC
10. Able to provide written informed consent

Exclusion Criteria:

1. Current use of steroid (except short course steroid for IRIS) and other immunosuppressive agents.
2. Current use of any prohibited medications related to drug pharmacokinetics.
3. 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.
4. Unlikely to be able to remain in follow-up for the protocol defined period.
5. Patients with proven or suspected acute hepatitis. Patients with chronic viral hepatitis are eligible provided ALT, AST \< 5 x ULN.
6. Karnofsky performance score \<30%

Primary outcomes:
measure: plasma concentration level
timeFrame: 12 hours
Secondary outcomes:
measure: identify toxicities
timeFrame: 48 weeks
measure: CD4
timeFrame: 48 weeks
measure: HIV RNA
timeFrame: 48 weeks
measure: genotypic resistant
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Bangkok
country: Thailand
facility: HIV-NAT Thai Red Cross AIDS Research Center
Study officials:
affiliation: The HIV Netherlands Australia Thailand Research Collaboration
name: Anchalee Avihingsanon, MD
role: PRINCIPAL_INVESTIGATOR
References: