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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

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ClinicalTrials.gov Identifier: NCT01138202
Recruitment Status : Completed
First Posted : June 7, 2010
Last Update Posted : February 22, 2016
Information provided by (Responsible Party):

Study Description
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.

Condition or disease Intervention/treatment Phase
HIV Infections Tuberculosis Drug: LPV/r Phase 2

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 .

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
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 Start Date : November 2010
Primary Completion Date : December 2015
Study Completion Date : December 2015

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: 1
boosted LPV/r 400/100 mg BID + 2 NRTI
Drug: LPV/r
LPV/r 400/100 mg BID + 2 NRTI for arm 1 (total 48 weeks) LPV/r 600/150 mg BID + 2 NRTI for arm 2 (total 48 weeks)
Experimental: 2
boosted LPV/r 600/150 mg BID + 2 NRTI
Drug: LPV/r
LPV/r 400/100 mg BID + 2 NRTI for arm 1 (total 48 weeks) LPV/r 600/150 mg BID + 2 NRTI for arm 2 (total 48 weeks)

Outcome Measures

Primary Outcome Measures :
  1. plasma concentration level [ Time Frame: 12 hours ]
    Percentage of plasma concentration level above an acceptable lower limit (lopinavir Cmin > 1 mg/L) at steady-state.

Secondary Outcome Measures :
  1. toxicity [ Time Frame: 48 weeks ]
    Toxicity of combined treatment for TB and HIV infections - the established DAIDS/ACTG toxicity grading scale of clinical and laboratory toxicities will be used.

  2. CD4 [ Time Frame: 48 weeks ]
    CD4 response (mean CD4 rise from baseline)

  3. HIV RNA [ Time Frame: 48 weeks ]
    HIV RNA response (% < 50 copies/ml at week 12, 24 and 48)

  4. genotypic resistant [ Time Frame: 48 weeks ]
    The emergence of NRTI and/or lopinavir genotypic resistant and its clinically

Eligibility Criteria

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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%
Contacts and Locations

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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01138202

HIV-NAT Thai Red Cross AIDS Research Center
Bangkok, Thailand, 10330
Sponsors and Collaborators
The HIV Netherlands Australia Thailand Research Collaboration
Department of Disease Control, Ministry of Public Health Thailand
Principal Investigator: Anchalee Avihingsanon, MD The HIV Netherlands Australia Thailand Research Collaboration
More Information

Additional Information:
Responsible Party: The HIV Netherlands Australia Thailand Research Collaboration
ClinicalTrials.gov Identifier: NCT01138202     History of Changes
Other Study ID Numbers: HIV-NAT 104
First Posted: June 7, 2010    Key Record Dates
Last Update Posted: February 22, 2016
Last Verified: February 2016

Keywords provided by The HIV Netherlands Australia Thailand Research Collaboration:
rifampicin containing anti-tuberculosis therapy
Pharmacokinetics and safety of Lopinavir/ritonavir with rifampicin containing anti-tuberculosis therapy

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Antitubercular Agents
Reverse Transcriptase Inhibitors
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Antibiotics, Antitubercular