Antiretroviral Therapy during Tuberculosis Treatment Improves Survival
antiretroviral therapy (ART) 2 weeks rather than 2 months
after beginning tuberculosis (TB) treatment led to longer
survival for HIV positive people with severe immune deficiency
in the CAMELIA study, researchers reported at the XVIII International
AIDS Conference (AIDS 2010) last
week in Vienna. Cambodian patients receiving early ART were
more likely to develop immune reconstitution inflammatory
syndrome (IRIS), but this was generally manageable and starting
sooner reduced mortality by more than 30%.
is the text of a press release from the National Institute of Allergy
and Infectious Diseases (NIAID), which partially funded the research,
describing the study findings and their implications.
NIH-Funded Study Finds
Early HAART during TB Treatment
Boosts Survival Rate in People Co-Infected with HIV and TB
clinical trial in Cambodia has found it possible to prolong the survival
of untreated HIV-infected adults with very weak immune systems and newly
diagnosed tuberculosis (TB) by starting anti-HIV therapy two weeks after
beginning TB treatment, rather than waiting eight weeks, as has been
standard. This finding by scientists co-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, brings physicians closer to optimizing the treatment of severely
immunosuppressed individuals with HIV-TB co-infection. The findings
were presented today at the XVIII International AIDS Conference in Vienna
by principal investigators Francois-Xavier Blanc, MD, Anne E. Goldfeld,
MD, and Sok Thim, MD.
"These results are just one example of how our best science can
advance the treatment of an important disease, TB, that exacts a huge
toll among HIV-infected individuals," says NIAID Director Anthony
S. Fauci, MD. "With an estimated 1.4 million HIV-infected individuals
developing TB in 2008 alone, we must continue to pursue 21st-century
solutions to the scourge of HIV-TB co-infection, as well as other diseases
that afflict HIV-infected people."
Individuals with HIV-TB co-infection in resource-limited countries frequently
come to the attention of healthcare professionals for the first time
when HIV already has severely damaged their immune systems. Such people
often die during the first few months after beginning TB treatment.
Clinicians agree that starting anti-HIV therapy during that short window
can stave off death for some patients, but data on the best time to
start have proven inconclusive and opinions have varied. The dilemma
is that starting anti-HIV therapy before the TB infection is under control
can cause the patient to become very sick and even die from a condition
known as Immune Reconstitution Inflammatory Syndrome, but starting anti-HIV
therapy too late may allow the patient to die from HIV infection. TB
accounted for nearly a quarter of HIV-related deaths worldwide in 2008.
The clinical trial, called the Cambodian Early versus Late Introduction
of Antiretroviral Drugs (CAMELIA), or ANRS 1295, launched in January
2006 at five sites in Cambodia, a country with a high prevalence of
TB and HIV. The study staff enrolled 661 volunteers ages 18 and older
with newly diagnosed HIV-TB co-infection and very weak immune systems
(measured as fewer than 200 CD4+ T cells per cubic millimeter of blood).
The participants all began receiving treatment for TB and were assigned
at random to begin antiretroviral therapy for HIV either two weeks later
or eight weeks later. The volunteers received powerful antiretroviral
drug cocktails known as highly active antiretroviral therapy, or HAART.
Study staff followed the participants for 50 weeks after the last volunteer
had enrolled in the trial, performing clinical exams and biological
tests at frequent intervals to monitor participants' health and safety.
By the end of the follow-up period, 59 out of 332 participants who had
started HAART two weeks after beginning TB treatment had died, while
90 out of 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, rather than waiting eight
weeks, boosts the chance of survival for people with HIV-TB co-infection
and severely damaged immune systems.
CAMELIA was conducted within the research agenda of the Cambodian National
Center for HIV/AIDS, Dermatology and STD under the leadership of Dr.
Blanc of Bicetre University Hospital, France; Dr. Goldfeld of Harvard
Medical School, Boston; and Dr. Sok of the Cambodian Health Committee,
Phnom Penh. NIAID provided funding for the study to the Cambodian Health
Committee via a grant from the Comprehensive International Program for
Research on AIDS.
For more information about CAMELIA, please see Questions
and Answers: The CAMELIA Clinical Trial.
affiliations: Pneumology Unit, Internal Medicine Department, Bicêtre
Hospital, Assistance Publique - Hôpitaux de Paris, Le Kremlin-Bicêtre,
Paris, France; Cambodian Health Committee, Phnom Penh, Cambodia; European
George Pompidou Hospital, Assistance Publique - Hôpitaux de Paris,
Paris, France; Institut Pasteur in Cambodia, Phnom Penh, Cambodia; Agence
Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS),
Paris, France; Institut Pasteur, Paris, France; Khmer Soviet Friendship
Hospital, Infectious Diseases Department, Phnom Penh, Cambodia; Donkeo
Provincial Hospital, Takeo, Cambodia; Médecins Sans Frontières,
Cambodia, Phnom Penh, Cambodia; Svay Rieng Provincial Hospital, Svay
Rieng, Cambodia; Calmette Hospital, Phnom Penh, Cambodia; Siem Reap
Referral Hospital, Siem Reap, Cambodia; Khmer Soviet Friendship Hospital,
Pneumology Department, Phnom Penh, Cambodia; Division of AIDS, NIAID,
National Institutes of Health, Bethesda, MD; Harvard Medical School,
Blanc, T Sok, D Laureillard, and others. 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. XVIII International
AIDS Conference. Vienna, July 18-23, 2010. Abstract THLBB106.
NIH-Funded Study Finds Early HAART during TB Treatment Boosts Survival
Rate in People Co-Infected with HIV and TB. NIH News. July 22, 2010.