NEW YORK (Reuters Health) – The dilemma of when to start antiretroviral therapy (ART) in patients presenting with tuberculous meningitis associated with HIV infection has been answered by the findings of a study conducted in Vietnam: immediate initiation of ART after starting TB therapy does not improve outcomes and adverse effects are worse than when ART is deferred.

The findings are reported in the June 1st issue of Clinical Infectious Diseases by Dr. M. Estee Torok, with Cambridge University Hospitals NHS Foundation Trust in the UK, and a multinational team of colleagues.

As they explain, the best time to begin antiretroviral therapy in patients with HIV and tuberculosis is controversial. Starting ART early with TB treatment is potentially complicated by drug toxicities, interactions and immune reconstitution inflammatory syndrome, while delaying ART may lead to HIV progression. These issues are even more critical in treating tuberculous meningitis, the most severe form of TB.

The investigators therefore conducted a randomized trial of immediate ART, begun within 7 days of starting TB treatment, versus deferred ART, initiated after 2 months of TB treatment, in 235 patients with HIV-associated tuberculous meningitis recruited in Ho Chi Minh City.

ART consisted of zidovudine, lamivudine, and efavirenz, and standard antituberculosis treatment was given with adjunctive dexamethasone and prophylactic co-trimoxazole.

In the 9 months following randomization, 76 patients in the immediate ART group died compared with 70 in the deferred group (hazard ratio 1.12, p=0.50), according to the report.

“Indeed, the overall mortality among patients with HIV-associated TBM (tuberculous meningitis) who were treated with ART was surprisingly similar to that among historical patients who did not receive ART during tuberculosis treatment,” the authors comment.

Severe adverse events (grade 3 or 4) occurred very frequently in both arms of the study, but significantly more patients in the immediate ART group than the deferred group experienced grade 4 adverse events (102 vs 87, respectively; p=0.04), the researchers found.

These results suggest “that it may be safer to defer initiation of ART in patients presenting with HIV-associated TBM,” Dr. Torok and colleagues conclude.

In reviewing the timing of ART during different opportunistic infections in different populations, the authors of an accompanying editorial comment: “In the case of TB meningitis in Vietnam, the stark reality may be that the prognosis of the patients is so poor that adjustments in the timing of ART are largely futile.”

The study authors add, “Our findings emphasize the need for early diagnosis and treatment of HIV infection, before patients present with advanced disease and life threatening opportunistic infections such as TBM.”

Timing of Initiation of Antiretroviral Therapy in Human Immunodeficiency Virus (HIV)–Associated Tuberculous Meningitis
Clin Infect Dis 2011;52:1374-1383.