Early vs Late Introduction of Antiretroviral Therapy in HIV-infected Patients With Tuberculosis (ANRS 1295 CAMELIA)
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|ClinicalTrials.gov Identifier: NCT00226434|
Recruitment Status : Completed
First Posted : September 27, 2005
Last Update Posted : March 16, 2012
In Cambodia the prevalence of both tuberculosis (TB) and Human Immunodeficiency Virus (HIV) infection is high. Data suggest that aggressive management of HIV infection, which includes Anti-Retroviral Therapy (HAART) during treatment of TB, decreases both morbidity and mortality. On the other hand, the use of HAART for patients with TB may cause severe complications due to drug-drug interactions, and occasionally a temporary exacerbation of symptoms. These reactions may be particularly severe when HAART is started soon after the start of TB treatment.
The proposed study aims to determine the optimal time to initiate HAART in previously untreated HIV-infected adult patients with TB and low CD4 cell counts.
|Condition or disease||Intervention/treatment||Phase|
|HIV Infection Tuberculosis||Procedure: Early antiretroviral treatment Procedure: Late antiretroviral treatment||Phase 3|
In Cambodia the prevalence of both tuberculosis (TB) and Human Immunodeficiency Virus (HIV) infection is high. In 2000, there were approximately 75.000 newly diagnosed TB cases. In 2003, 1.9% of the population was infected with HIV. TB rates in Cambodia are more than double those observed in other developing countries and up to 30 times higher than those currently seen in the USA or Western Europe. It is estimated that over 8% of the newly diagnosed TB cases are co-infected with HIV, of which approximately 85% are severely immunosuppressed (CD4+ cell count < 200 x 106 cells/l).
Mortality rates were found to be 2-4 folds higher in HIV/TB co-infected patients than in TB alone. Data suggest that aggressive management of HIV infection, which includes Highly Active Anti-Retroviral Therapy (HAART) during treatment of TB decreases both morbidity and mortality by suppressing viral replication and improving immune function.
On the other hand, the use of HAART for patients with TB may cause severe complications due to drug-drug interactions, and occasionally a temporary exacerbation of symptoms, signs or radiographic manifestations of TB. Such events or 'paradoxical reactions' that occur among 7 - 36% of HIV/TB co-infected patients treated with HAART may be secondary to immune restitution. These reactions may be particularly severe when HAART is started soon after the start of TB treatment.
Most clinical teams recommend delaying the initiation of HAART to avoid the early side effects of TB treatment and simplify clinical management of the co-infected patient. However others argue that early initiation of HAART in TB patients with CD4 cell counts < 100 x 106 cells/l leads to a marked reduction of viral load despite frequent adverse events.
The proposed study aims to determine the optimal time to initiate HAART (defined as d4T + 3TC + efavirenz) in previously untreated HIV-infected adult patients with TB and low CD4 cell counts. The study is a multicentre prospective, randomized, open-label two-armed trial with no placebo. It is designed as a superiority trial to compare the "early arm" (HAART initiated 2 weeks after TB treatment onset) with the "late arm" (HAART initiated 2 months after TB treatment onset). Efficacy will be assessed by the survival rate in the two arms. Secondary objectives will include evaluation of (1) the safety of an early initiation of HAART in terms of drug interactions or paradoxical reactions, (2) the occurrence of opportunistic infections diagnosed during the follow-up period, (3) patients' adherence to TB treatment and HAART, (4) the rate of hospitalization for any cause during the trial; the measure of (5) the effectiveness of the TB treatment and HAART and (6) the predictive factors for the survival, the response to anti-TB therapy and HAART and the paradoxical reactions.
The total study duration is expected to be 4 years (3 years for enrolment and at least one year of follow-up) in five study sites: (1) Khmero-Soviet Friendship Hospital, Phnom Penh; (2) Calmette Hospital, Phnom Penh; (3) Provincial hospital, Svay Rieng province; and (4) Provincial hospital, Takeo province, (5) Provincial Hospital, Siem Reap.
The study will be carried out in compliance with the protocol and in accordance with the Declaration of Helsinki approved by the World Health Association and with the recommendations of the Good Clinical Practice.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||661 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Early vs Late Introduction of Antiretroviral Therapy in Naive HIV-infected Patients With Tuberculosis in Cambodia|
|Study Start Date :||January 2006|
|Actual Primary Completion Date :||May 2010|
|Actual Study Completion Date :||May 2010|
Procedure: Early antiretroviral treatment
The ARV treatment is started 2 weeks after the diagnosis and the start of the anti-tuberculosis treatment
|Active Comparator: 2||
Procedure: Late antiretroviral treatment
The ARV treatment is started 8 weeks after the diagnosis and the start of the anti-tuberculosis treatment
- Survival rate [ Time Frame: At the end of the study ]
- Type, frequency and severity of Adverse Events that occur during the trial and to their potential relations with the drugs, HIV or TB infection [ Time Frame: During the overall study ]
- Frequency of Immune Reconstitution Inflammatory Syndrome [ Time Frame: During the overall study ]
- Frequency of TB paradoxical reaction, defined as worsening or emergence of signs or symptoms of TB (e.g. fever, cough, shortness of breath, adenopathy or exacerbation of disease at other extra pulmonary sites) during appropriate TB treatment [ Time Frame: During the overall study ]
- Occurrence of opportunistic infections [ Time Frame: During the overall study ]
- Evaluation of TB treatment success [ Time Frame: During the overall study ]
- Evaluation of ART treatment success [ Time Frame: During the overall study ]
- Resistance to ARV treatment determined by genotyping HIV-1 strains among patients with detectable viral load on Day 0 and Week 50 [ Time Frame: Within 12 months of follow-up ]
- Patient's adherence to TB and ARV treatment evaluated based on interviews and pill counts at each study visit [ Time Frame: During the overall study ]
- Pharmacokinetic study to assess efavirenz plasma exposure will be assayed at regular time intervals [ Time Frame: Within 12 months of follow-up ]
- Survival Rate [ Time Frame: 50 weeks after enrolment ]
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): NCT00226434
|Phnom Penh, Cambodia|
|Khmero-Soviet Friendship Hospital|
|Phnom Penh, Cambodia|
|Siem Reap Referral Hospital|
|Siem Reap, Cambodia|
|Svay Rieng, Cambodia|
|Principal Investigator:||François-Xavier Blanc||Bicêtre University Hospital, France|
|Principal Investigator:||Thim Sok||Cambodian Health Committee, Phnom Penh, Cambodia|
|Principal Investigator:||Anne Goldfeld||Institute for Biomedical Research, Boston, USA|