Phnom Penh, Cambodia — A randomized clinical trial carried out by Cambodian, French and American collaborators in Cambodia has shown that survival is dramatically enhanced in people co-infected with HIV and tuberculosis when treatment for HIV is started rapidly after initiation of tuberculosis treatment. The results, to be presented July 22 at the XVIII International AIDS Conference in Vienna, answer an important question about the timing of the complicated treatment regimen required to successfully treat this common and deadly co-infection in resource-limited countries.
"Our results can be implemented into clinical practice without delay, to better use medicines we already have in hand to save countless lives around the world," says Dr. Thim Sok, co-founder and director of the Cambodian Health Committee (CHC), a nonprofit, nongovernmental health organization that has been working since 1994 to build treatment and research programs for TB and HIV in Cambodia. Sok is one of three principle investigators of the study, together with Dr. F. Xavier Blanc of France and CHC co-founder Dr. Anne Goldfeld of the United States.
The trial, the first of its kind to be carried out in Cambodia, was initiated by CHC together with the French National Agency for Research on AIDS and Viral Hepatitis (ANRS) and funded by both the ANRS and the U.S. National Institutes of Health Comprehensive International Program for Research on AIDS (CIPRA). The study also included collaborators from the Pasteur Institute of Cambodia, and Doctors Without Borders-Belgium. "We are proud that this trial was conducted in Cambodia. It required much effort and the building of a research infrastructure basically from scratch starting almost a decade ago," says Sok.
"We imagine that these findings will make a major impact on mortality due to TB and HIV co-infection globally. We expect that treatment recommendations will change and that millions of lives could be saved, " says Professor Eng Huot, the Cambodian Secretary of State for Health.
The twin spread of tuberculosis and AIDS has created a human tragedy and a growing medical crisis for the developing world. An estimated 1.37 million people worldwide have HIV/tuberculosis co-infection, and 456,000 die every year. One quarter of all deaths among HIV-infected people are from tuberculosis.
From a clinical perspective, the treatment of co-infected patients is challenging, requiring the simultaneous administration of two complicated drug regimens. The current practice is to initiate TB treatment first, followed later by the cocktail of anti-HIV drugs. However, the optimal timing for the introduction of AIDS drugs after TB therapy was unknown, especially within the timeframe of the first two months after diagnosis when mortality is the highest.
The CAMbodian Early vs. Late Introduction of Antiretrovirals (CAMELIA) trial tested whether starting severely immunodeficient AIDS patients on antiretroviral medication (AIDS drugs) two weeks or eight weeks after beginning their TB treatment results in better survival.
Conducted between 2006 and 2010, the trial treated 661 patients co-infected with HIV and tuberculosis in five hospitals in Cambodia. The patients were all severely immunocompromised, and started standard tuberculosis treatment as soon as they were included in the study. Half of the patients started triple-drug therapy against HIV two weeks after beginning TB treatment, and the other half eight weeks after. The results showed that significantly more patients died in the 8 week treatment group than in the 2 week group. Overall, the risk of death was reduced by 34% by early treatment significantly reducing mortality.
"This answer comes from the grassroots and the suffering of Cambodia and it will relieve the suffering of countless people throughout the world afflicted by TB and AIDS. This gives us much satisfaction," adds Huot.
Significant enhancement in survival with early (2 weeks) vs. late (8 weeks) initiation of highly active antiretroviral treatment (HAART) in severely immunosuppressed HIV-infected adults with newly diagnosed tuberculosis.
F.X. Blanc1, T. Sok2, D. Laureillard2,3, L. Borand4, C. Rekacewicz5, E. Nerrienet4, Y. Madec6, O. Marcy2, S. Chan2, N. Prak7, C. Kim8,9, K.K. Lak2,10, C. Hak11, B. Dim2,9,12, C.I. Sin13, S. Sun2,10, B. Guillard4, B. Sar4, S. Vong4, M. Fernandez2, L. Fox14, J.F. Delfraissy5, A.E. Goldfeld2,15
1. Pneumology Unit, Internal Medicine Department, Bicêtre Hospital, Assistance Publique - Hôpitaux de Paris, Le Kremlin-Bicêtre, France
2. Cambodian Health Committee, Phnom Penh, Cambodia
3. European George Pompidou Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France
4. Institut Pasteur in Cambodia, Phnom Penh, Cambodia
5. Agence nationale de recherche sur le sida et les hépatites virales (ANRS), Paris, France
6. Institut Pasteur, Paris, France
7. Khmer Soviet Friendship Hospital, Infectious Diseases Department, Phnom Penh, Cambodia
8. Donkeo Provincial Hospital, Takeo, Cambodia
9. Médecins Sans Frontières, Cambodia, Phnom Penh, Cambodia
10. Svay Rieng Provincial Hospital, Svay Rieng, Cambodia
11. Calmette Hospital, Phnom Penh, Cambodia
12. Siem Reap Referral Hospital, Siem Reap, Cambodia
13. Khmer Soviet Friendship Hospital, Pneumology Department, Phnom Penh, Cambodia
14. Division of AIDS, NIAID, National Institutes of Health (NIH), Bethesda, United States
15. Immune Disease Institute, Harvard Medical School, Boston, United States and the Cambodian Health Committee
International Aids Society Conference, Vienna, Late Breaker presentation, July 22nd, 2010
About the Cambodian Health Committee (CHC) (www.globalhealthcommittee.org):
Founded in Cambodia in 1994, with a base in Boston, CHC has treated and cured thousands of Cambodians of tuberculosis and provides HIV/AIDS care for thousands more. CHC's mission is to focus on those suffering from tuberculosis (TB) and AIDS, who are among the poorest in our global society. CHC operates from the core belief that good practice depends upon knowledge developed through grassroots experience and rigorous research. Now also known as the Global Health Committee, CHC is bringing its unique delivery models of care for TB and AIDS, including for drug-resistant TB, to Africa. With its strategy of delivery of care, discovery of new knowledge, and advocacy, CHC is developing global models of care while curing TB and treating AIDS one person at a time.