Santiago Moreno, MD
In adults with HIV infection and newly diagnosed tuberculosis (TB), does timing of initiation of antiretroviral therapy (ART) after start of anti-TB therapy affect mortality?
Randomized controlled trial (Cambodian Early versus Late Introduction of Antiretrovirals [CAMELIA] trial). ClinicalTrials.gov NCT01300481.
{Allocation concealed}*.†
Unblinded.†
Median 25 months.
5 hospitals in Cambodia.
661 inpatients and outpatients ≥ 18 years of age (median age 35 y, 64% men) who had HIV infection, CD4+ T-cell count ≤ 200 cells/mm3 in the previous 14 days, no previous ART, and a new diagnosis of pulmonary or extrapulmonary TB (positive smear for acid-fast bacilli), with start of TB treatment < 1 week before enrollment. Exclusion criteria included impaired hepatic function, treatment for previous TB, and pregnancy or breastfeeding.
Earlier (2 weeks, n = 332) or later (8 weeks, n = 329) initiation of ART (stavudine, lamivudine, and efavirenz according to Cambodian national guidelines) after start of anti- TB therapy (isoniazid, rifampin, ethambutol, and pyrazinamide daily for 2 mo, followed by isoniazid and rifampin daily for 4 mo).
Primary outcome was mortality. Secondary outcomes included cured TB, TB-associated immune reconstitution inflammatory syndrome (IRIS) (worsening or emergence of TB symptoms after start of ART, with no evidence of newly acquired infection; evolution of drug-resistant tuberculosis; infection with a previously identified pathogen; or side effects of ART), CD4+ T-cell counts, and undetectable viral load (< 2.4 log10 [250] copies/mm).
96% completed follow-up or died (intention-to-treat analysis).
Earlier ART reduced mortality but increased TB-associated IRIS more than later ART (Table). Earlier and later ART did not differ for cured TB (48% vs 45%, {P = 0.42}‡), CD4+ T-cell counts (median gain 118 vs 112 cells/mm3, P = 0.22), or patients with undetectable viral load (P = 0.82).
In adults with HIV and newly diagnosed tuberculosis (TB), earlier initiation of antiretroviral therapy within 2 weeks after start of anti-TB therapy reduced mortality but increased TB-associated immune reconstitution inflammatory syndrome.
§IRIS = immune reconstitution inflammatory syndrome; other abbreviations defined in Glossary. RRR, RRI, NNT, and NNH calculated from control event rates and hazard ratios in article.
||Adjusted for study site and CD4+ T-cell count at baseline.
Moreno S. Earlier initiation of antiretroviral therapy after start of antituberculosis therapy reduced mortality in HIV. Ann Intern Med. ;156:JC3–2. doi: 10.7326/0003-4819-156-6-201202210-02002
Download citation file:
© 2019
Published: Ann Intern Med. 2012;156(6):JC3-2.
DOI: 10.7326/0003-4819-156-6-201202210-02002
HIV, Infectious Disease, Mycobacterial Infections.
Results provided by: