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

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

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections; Tuberculosis
• Intervention / Treatment: Drug: LPV/r

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 Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• Thailand
  • Bangkok, Thailand, 10330
    • HIV-NAT Thai Red Cross AIDS Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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%

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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)

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
identify toxicities	Toxicity of combined treatment for TB and HIV infections - the established DAIDS/ACTG toxicity grading scale of clinical and laboratory toxicities will be used.	48 weeks
CD4	CD4 response (mean CD4 rise from baseline)	48 weeks
HIV RNA	HIV RNA response (% < 50 copies/ml at week 12, 24 and 48)	48 weeks
genotypic resistant	The emergence of NRTI and/or lopinavir genotypic resistant and its clinically	48 weeks

Collaborators and Investigators

• Sponsor: The HIV Netherlands Australia Thailand Research Collaboration
• Collaborators: Department of Disease Control, Ministry of Public Health Thailand
• Investigators: Principal Investigator: Anchalee Avihingsanon, MD, The HIV Netherlands Australia Thailand Research Collaboration

Publications and helpful links

Helpful Links

• HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT)

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: June 4, 2010
• First Submitted That Met QC Criteria: June 4, 2010
• First Posted (Estimate): June 7, 2010

Study Record Updates

• Last Update Posted (Actual): July 17, 2020
• Last Update Submitted That Met QC Criteria: July 15, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: safety; pharmacokinetics; efficacy; Lopinavir/ritonavir; HIV/TB; rifampicin containing anti-tuberculosis therapy; Pharmacokinetics and safety of Lopinavir/ritonavir with rifampicin containing anti-tuberculosis therapy
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis
• Other Study ID Numbers: HIV-NAT 104