Thursday, July 22, 2010
1. What is the CAMELIA clinical trial?
CAMELIA, which stands for Cambodian Early versus Late Introduction of Antiretroviral Drugs, was a Phase III clinical trial designed to determine the best time to start anti-HIV therapy in people who are co-infected with HIV and tuberculosis (TB), who have just begun treatment for TB, and whose immune systems are severely damaged by HIV. The study addressed the dilemma that starting anti-HIV therapy before an individual’s TB infection is under control can lead to a serious and even fatal condition called Immune Reconstitution Inflammatory Syndrome, yet starting anti-HIV therapy too late may allow the patient to die from HIV infection. The trial, also known as ANRS 1295, compared whether the chance of survival is greater if such individuals start taking an anti-HIV drug cocktail two weeks after beginning treatment for TB or eight weeks after beginning treatment for TB.
2. Who conducted and funded this study?
The study was conducted within the research agenda of the Cambodian National Center for HIV/AIDS, Dermatology and STD under the leadership of principal investigators François-Xavier Blanc, M.D., of Bicêtre University Hospital, Le Kremlin-Bicêtre, France; Anne E. Goldfeld, M.D., of Harvard Medical School, Boston; and Sok Thim, M.D., of the Cambodian Health Committee, Phnom Penh.
The study was sponsored and funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and the French National Agency for Research on AIDS and Viral Hepatitis (ANRS). NIAID funded the study through a grant from the Comprehensive International Program for Research on AIDS.
3. Why was CAMELIA conducted?
When CAMELIA was designed, the current World Health Organization recommendation was that HIV-infected individuals with newly diagnosed TB and very weak immune systems should begin taking anti-HIV treatment known as highly active antiretroviral therapy (HAART) between two and eight weeks after starting TB treatment. This recommendation of a delay of up to eight weeks was designed to minimize severe complications from TB-HIV drug interactions and illness or death from Immune Reconstitution Inflammatory Syndrome. At the same time, other data suggested that administering HAART sooner than eight weeks after the start of TB treatment would decrease the risk of illness and death in HIV-TB co-infected individuals with grave immune-system damage by helping their immune systems fight both diseases better. These observations led to conflicting opinions about the best time to start HAART in the population of concern. The medical community needed a randomized clinical trial to help resolve the dilemma. CAMELIA was designed to meet this need.
4. Who participated in CAMELIA?
The study participants were 661 Cambodian men and women ages 18 and older who were co-infected with HIV and TB, had fewer than 200 CD4+ T cells per cubic millimeter (mm3) upon enrollment in the trial, had never been treated for HIV, and either had never received TB treatment or had started no more than a week before enrollment.
At the beginning of the study, the participants had a median age of 35 years and a median CD4+ T cell count of 25 cells/mm3, a sign of extremely poor immune function due to untreated HIV infection.
5. When and where did CAMELIA take place?
CAMELIA took place between January 2006 and May 2010 at five sites in Cambodia:
6. What was the study design?
All participants began receiving treatment for TB no more than a week before enrollment in the study or shortly after enrollment. Then they were assigned at random to begin HAART either two weeks after starting TB treatment or eight weeks after starting TB treatment.
The TB treatment regimen lasted 26 weeks and consisted of daily rifampicin, isoniazid, ethambutol and pyrazinamide for the first two months, followed by daily rifampicin and isoniazid for the remaining four months. Pyridoxine was given as a supplement throughout this period. The HAART regimen consisted of daily stavudine, lamivudine and efavirenz. Both regimens were in keeping with the standard of care for treating HIV-TB co-infection in Cambodia.
Study staff followed the participants for 50 weeks after the last volunteer enrolled in the trial, performing clinical exams and biological tests at frequent intervals to monitor participants’ health and safety.
7. How was TB diagnosed in study participants?
Fluid was gathered from potential participants in the form of sputum, lymph node drainage, stool, cerebrospinal fluid, or pleural fluid. Individuals whose fluid sample tested positive for acid-fast bacteria were eligible for the study. The sample was then cultured in a lab to see if the TB bacterium, Mycobacterium tuberculosis, would grow. If the bacteria were growing, this positive culture confirmed the diagnosis of TB.
8. What were the results of the study?
By May 2010, the end of the follow-up period, 59 of the 332 participants who had started HAART two weeks after beginning TB treatment had died, while 90 of the 329 participants who started HAART eight weeks after beginning TB treatment had died. This 33 percent difference was statistically significant, leading the principal investigators to conclude that starting HAART two weeks after beginning TB treatment boosts the chance of survival for people with HIV-TB co-infection and severely damaged immune systems.
At that time, the study investigators also found that the presence of HIV RNA was undetectable in 96.5 percent of the surviving participants, meaning HAART had successfully controlled the virus in those individuals.
9. Are the surviving participants continuing to receive treatment for HIV now that the study has ended?
Yes. Physicians at the study sites are continuing to provide HAART regimens to the surviving participants, with antiretroviral drugs supplied by the Cambodian National Center for HIV/AIDS, Dermatology and STD.
10. Have the results of CAMELIA changed the standard of care in Cambodia for HIV-TB co-infection in people with severely damaged immune systems?
Yes. In response to the results of CAMELIA, the Cambodian Ministry of Health has changed its national standard of care for patients co-infected with TB and HIV to begin HAART two weeks after starting TB treatment.
For more information about the CAMELIA clinical trial, please see NIH-Funded Study Finds Early HAART during TB Treatment Boosts Survival Rate in People Co-Infected with HIV and TB.
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Last Updated July 21, 2010
Last Reviewed July 22, 2010