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
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
1Pneumology Unit, Internal Medicine Department, Bicêtre Hospital, Assistance Publique - Hôpitaux de Paris, Le Kremlin-Bicêtre, France, 2Cambodian Health Committee, Phnom Penh, Cambodia, 3European George Pompidou Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France, 4Institut Pasteur in Cambodia, Phnom Penh, Cambodia, 5Agence Nationale de Recherche sur le SIDA et les hépatites virales (ANRS), Paris, France, 6Institut Pasteur, Paris, France, 7Khmer Soviet Friendship Hospital, Infectious Diseases Department, Phnom Penh, Cambodia, 8Donkeo Provincial Hospital, Takeo, Cambodia, 9Médecins Sans Frontières, Cambodia, Phnom Penh, Cambodia, 10Svay Rieng Provincial Hospital, Svay Rieng, Cambodia, 11Calmette Hospital, Phnom Penh, Cambodia, 12Siem Reap Referral Hospital, Siem Reap, Cambodia, 13Khmer Soviet Friendship Hospital, Pneumology Department, Phnom Penh, Cambodia, 14Division of AIDS, NIAID, National Institutes of Health (NIH), Bethesda, United States, 15Harvard Medical School, Boston, United States
Background: Tuberculosis (TB) remains the largest cause of death
among people living with HIV/AIDS, especially among those with profound
immunosuppression. Case-fatality among co-infected patients occurs mainly in the first
months after TB treatment initiation. Therefore, robust data regarding optimal timing of HAART
initiation within this early period are critically needed.
(CAMbodian Early vs. Late Introduction of Antiretroviral drugs:
ANRS 1295/12160-CIPRA KH001/10425), an
open-labelled randomized clinical trial, was designed to compare the impact upon
mortality of early (2 weeks) vs. late (8 weeks) HAART initiation after TB treatment
onset in treatment-naïve adults with newly diagnosed acid-fast bacilli (AFB)
positive TB and CD4+ cell count < 200 cells/mm3.
Patients received standard 6-month TB treatment plus stavudine, lamivudine and
efavirenz in 5 sites in Cambodia and were followed through 50 weeks after the last
patient was enrolled. A log-rank test was used to compare Kaplan-Meier survival
patients (early, n=332; late, n=329) were enrolled. Median age was 35 years,
body mass index 16.7 kg/m2,
CD4+ cell count 25 cells/mm3 and viral load 5.64 log copies/ml. All AFB-positive samples, including sputum in 538 (81.4%)
patients, were cultured. As of May 13, 2010, 146 patients were known dead (59, early arm; 87, late
arm). Enhanced survival was
observed in the early arm (p< 0.01, figure). At week 50, median CD4+ gain
was 114 cells/mm3; 96.5% of patients had an undetectable viral load.
Conclusions: Initiation of HAART 2 weeks after onset
of TB treatment significantly improves survival in severely immunosuppressed
HIV-infected adults with newly diagnosed TB.
[Kaplan-Meier survival curves]
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