Appropriate Timing of HAART in Co-infected HIV/TB Patients (TIME)

Initiation of a Once Daily Regimen of Tenofovir, Lamivudine and Efavirenz After 4 Weeks Versus 12 Weeks of Tuberculosis Treatment in HIV-1 Infected Patients (Time Study)

To study the optimal timing to initiate antiretroviral therapy in HIV-infected patients who are receiving tuberculosis treatment between at 4 weeks and at 12 weeks after tuberculosis treatment by comparing the composite end point of death rate, hospitalization rate and adverse drug reactions at week 48, 96 and 144.

Study Overview

• Status: Terminated
• Conditions: HIV Infections; Tuberculosis
• Intervention / Treatment: Drug: tenofovir, lamivudine, efavirenz

Detailed Description

The growing epidemic of HIV poses a serious public health threat in many countries, including Thailand. Mortality is clearly reduced in HIV and tuberculosis (TB) co-infected patients who initiate antiretroviral therapy (ART) after the treatment of TB, but the optimal timing to initiate ART is one of the major concern for patients concurrently receiving both therapies. To date, the prospective, randomized, control trial to study the optimal timing to initiate ART in the patients is still limited. In addition, the current recommendation to start ART in patients co-infected with HIV and TB is still based on expert opinions. Here, the investigators plan to investigate the optimal timing to initiate antiretroviral therapy in HIV-infected patients who are receiving tuberculosis treatment between at 4 weeks and at 12 weeks after tuberculosis treatment by comparing the composite end point of death rate, hospitalization rate and adverse drug reactions at week 48, 96 and 144 at Bamrasnaradura Infectious Diseases Institute, Ministry of Public Health, Nonthaburi, Thailand.

• Study Type: Interventional
• Enrollment (Actual): 156
• Phase: Phase 4

Contacts and Locations

Study Locations

• Thailand
  • Nonthaburi, Thailand, 11000
    • Bamrasnaradura Infectious Diseases Institute, Ministry of Public Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 18-65 years of age
2. HIV-1 infected patients
3. Naïve to antiretroviral treatment
4. Baseline CD4 cell count <350 cells/mm3 at enrolment
5. Diagnosed as having active tuberculosis by clinical features or positive acid fast stain or positive TB culture; and receiving rifampicin containing antituberculous regimen
6. Signed inform consent

Exclusion Criteria:

1. Serum transaminase enzymes ≥ 5 times of upper normal limit or total bilirubin ≥ 3 times of upper normal limit
2. Serum creatinine ≥ 2 times of upper normal limit
3. Lactation or pregnancy
4. Receiving any immunosuppressive agents

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: start antiretroviral treatment; the optimal timing to initiate antiretroviral therapy in HIV-infected patients who are receiving tuberculosis treatment between at 4 weeks and at 12 weeks after tuberculosis treatment	Drug: tenofovir, lamivudine, efavirenz; initiate tenofovir 300 mg/day, lamivudine 300 mg/day, efavirenz 600 mg/day between at 4 weeks and at 12 weeks after tuberculosis treatment; Other Names: at 4 weeks versus at 12 weeks after tuberculosis treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
death rate	48 weeeks

Secondary Outcome Measures

Outcome Measure	Time Frame
hospitalization	48 weeks
adverse events	48 weeks
composite endpoint of a. death b. hospitalization and c. adverse event	48 weeks
TB IRIS	48 weeks
Risk of death	48 weeks

Collaborators and Investigators

• Sponsor: Bamrasnaradura Infectious Diseases Institute
• Collaborators: Thai Red Cross AIDS Research Centre; Mahidol University
• Investigators: Principal Investigator: Weerawat Manosuthi, MD, Bamrasnaradura Infectious Diseases Institute, Ministry of Public Health, Nonthaburi, Thailand

Publications and helpful links

General Publications

• Kiertiburanakul S, Manosuthi W, Sungkanuparph S. Optimal timing of antiretroviral therapy initiation in patients coinfected with HIV and tuberculosis. Expert Rev Clin Pharmacol. 2011 Mar;4(2):143-6. doi: 10.1586/ecp.11.2. No abstract available.

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (Actual): May 1, 2011
• Study Completion (Actual): May 1, 2011

Study Registration Dates

• First Submitted: November 16, 2009
• First Submitted That Met QC Criteria: November 16, 2009
• First Posted (Estimate): November 17, 2009

Study Record Updates

• Last Update Posted (Estimate): November 17, 2011
• Last Update Submitted That Met QC Criteria: November 16, 2011
• Last Verified: November 1, 2011

More Information

Terms related to this study

• Keywords: HIV; antiretroviral treatment; tuberculosis; timing
• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Tenofovir; Lamivudine; Efavirenz
• Other Study ID Numbers: 0435.3/1551