When to Start HIV Treatment in Previously Untreated HIV/TB Coinfected Individuals - Full Text View

Purpose

In Cambodia, the prevalence of tuberculosis (TB) and HIV infection is high. Treating TB/HIV coinfected individuals is difficult due to drug-drug interactions between TB treatment and Highly Active Antiretroviral Therapy (HAART). The purpose of this study is to determine when to start HAART in HIV/TB coinfected individuals with low CD4 counts who have not been on treatment before.

Condition	Intervention	Phase
HIV Infections Tuberculosis	Drug: Antiretroviral therapy (ARV) Drug: Tuberculosis (TB) treatment	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	CAMELIA: Early vs. Late Introduction of Antiretroviral Therapy in Naive HIV Infected Patients With Tuberculosis in Cambodia

Resource links provided by NLM:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: HIV/AIDS Tuberculosis

U.S. FDA Resources

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:

Survival at the end of the study [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Survival rate [ Time Frame: 50 weeks after enrollment ] [ Designated as safety issue: Yes ]
Safety [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Immune reconstitution syndrome [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Tuberculosis (TB) paradoxical reaction [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Occurence of opportunistic infections [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
TB recurrence [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Evaluation of antiretroviral therapy [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Resistance to ARV and TB treatment [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Adherence to TB and ARV treatment [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Enrollment:	661
Study Start Date:	January 2006
Study Completion Date:	May 2010
Primary Completion Date:	October 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 Early treatment with HAART: 2 weeks following starting treatment for TB	Drug: Antiretroviral therapy (ARV) Stavudine, lamivudine and efavirenz Drug: Tuberculosis (TB) treatment Rifampicin, isoniazid, ethambutol and pyrazinamide during the first 2 months of TB treatment; rifampicin and isoniazid during the last 4 months of TB treatment
Experimental: 2 Late treatment with HAART: 2 months following starting treatment for TB	Drug: Antiretroviral therapy (ARV) Stavudine, lamivudine and efavirenz Drug: Tuberculosis (TB) treatment Rifampicin, isoniazid, ethambutol and pyrazinamide during the first 2 months of TB treatment; rifampicin and isoniazid during the last 4 months of TB treatment

Detailed Description:

According to the World Health Organization (WHO), the the prevalence of TB in Cambodia is more than double that in other developing countries and up to 30 times higher than that in the United States or Western Europe. It is estimated that over 8 % of individuals newly diagnosed with TB are also HIV coinfected. The use of HAART in HIV/TB coinfected individuals effectively lowers the viral load and improves immune function; however, HAART has been shown to cause severe complications, including drug-drug interactions and a temporary exacerbation of TB symptoms. The purpose of this study is to determine the optimal time to initiate HAART (include drugs used here: d4T + 3TC + efavirenz?) in previously untreated HIV/TB coinfected individuals with low CD4 counts.

This study will last 3 years. Participants will be randomly assigned to either the "early" arm or the "late" arm. Participants in the early arm will receive HAART 2 weeks following starting treatment for TB. Participants in the late arm will receive HAART 2 months following starting treatment for TB. All participants will receive stavudine, lamivudine and efavirenz as part of the HAART regimen. Additionally, all participants will receive rifampicin, isoniazid, ethambutol and pyrazinamide during the first 2 months of TB treatment and isoniazid and rifampicin during the last 4 months of TB treatment. Study visits will occur two weeks after starting TB treatment, two weeks after starting HAART, every four weeks during the TB treatment phase, every two months until Week 58 and then at Week 78 study visits will occur every six months until the end of the study. A physical exam and blood tests will occur at every visit. At Weeks 0 and 26 of TB treatment, participants will receive a tuberculin skin test. Eye exams will occur at Weeks 0 and 8 of TB treatment. A chest X-ray will be performed at Weeks 0, 8, 26 and of TB treatment.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

HIV Infected
CD4 count of or less than 200 cells/ml within 14 days prior to study entry
Positive acid-fast bacilli (AFB) test on any type of smear (e.g., sputum, lymph node drainage, stool, cerebral spinal fluid, pleural fluid)
Antiretroviral therapy (ARV) treatment naive
Tuberculosis (TB) treatment started less than one week prior to study entry
Willing to use an acceptable method of contraception for the duration of the study

Exclusion Criteria:

HIV uninfected
CD4 count greater than 200 cells/ml
Suspected tuberculosis with negative AFB test
Impaired liver function
Unable to adhere to study procedures
Previous suspected or documented TB treatment
Previous ARV treatment
Pregnancy or breastfeeding

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01300481

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Principal Investigator:	Francois-Xavier Blanc	Internal Medicine Department, Bicetre University Hospital
Principal Investigator:	Sok Thim	Cambodian Health Committee
Principal Investigator:	Anne E. Goldfeld	CBR Institute for Biomedical Research, Harvard Medical School

More Information

Publications:

Burman WJ, Jones BE. Treatment of HIV-related tuberculosis in the era of effective antiretroviral therapy. Am J Respir Crit Care Med. 2001 Jul 1;164(1):7-12. Review. No abstract available.

Dean GL, Edwards SG, Ives NJ, Matthews G, Fox EF, Navaratne L, Fisher M, Taylor GP, Miller R, Taylor CB, de Ruiter A, Pozniak AL. Treatment of tuberculosis in HIV-infected persons in the era of highly active antiretroviral therapy. AIDS. 2002 Jan 4;16(1):75-83.

Schluger NW, Perez D, Liu YM. Reconstitution of immune responses to tuberculosis in patients with HIV infection who receive antiretroviral therapy. Chest. 2002 Aug;122(2):597-602.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Blanc FX, Sok T, Laureillard D, Borand L, Rekacewicz C, Nerrienet E, Madec Y, Marcy O, Chan S, Prak N, Kim C, Lak KK, Hak C, Dim B, Sin CI, Sun S, Guillard B, Sar B, Vong S, Fernandez M, Fox L, Delfraissy JF, Goldfeld AE; CAMELIA (ANRS 1295–CIPRA KH001) Study Team. Earlier versus later start of antiretroviral therapy in HIV-infected adults with tuberculosis. N Engl J Med. 2011 Oct 20;365(16):1471-81.

Responsible Party:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT01300481 History of Changes
Other Study ID Numbers:	CIPRA KH 001, ANRS 1295
Study First Received:	February 17, 2011
Last Updated:	October 26, 2012
Health Authority:	United States: Federal Government

Additional relevant MeSH terms:

HIV Infections
Acquired Immunodeficiency Syndrome
Tuberculosis
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral

Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections

ClinicalTrials.gov processed this record on May 16, 2013

When to Start HIV Treatment in Previously Untreated HIV/TB Coinfected Individuals (CAMELIA)