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and Hepatitis.com Coverage of the
18th Conference on Retroviruses and
Opportunistic Infections (CROI 2011)
February 27 - March 2, 2011, Boston, MA
Immediate ART Improves Survival for HIV+ People
People with tuberculosis (TB) who start antiretroviral therapy (ART) immediately upon HIV diagnosis were less likely to progress to AIDS or death in the multinational ACTG 5221 STRIDE study, according to a report at 18the Conference on Retroviruses and Opportunistic Infections (CROI 2011) this month in Boston.
For people with less advanced HIV disease and higher CD4 T-cell counts, however, a short delay of 8-12 weeks reduced the likelihood of developing immune reconstitution inflammatory syndrome (IRIS).
TB is a leading cause of death for people with HIV/AIDS worldwide and is considered an opportunistic infection. In general, people diagnosed with late-stage HIV disease or AIDS are advised to start combination ART right away. TB medications can interact with HIV drugs, however, and increase the frequency of adverse side effects, so the optimal time to start ART in patients with HIV/TB coinfection has been the subject of debate.
Diane Havlir and fellow investigators aimed to shed further light on the benefits of starting antiretroviral treatment early in HIV/TB coinfected patients with varying levels of immune dysfunction. ACTG 5221 was an open-label strategy trial comparing immediate ART (starting 2 weeks after TB treatment initiation) versus early ART (starting at 8-12 weeks).
The researchers enrolled more than 800 patients with confirmed or suspected TB at more than 20 sites on 4 continents. At entry, all participants had fewer than 250 cells/mm3. This level -- indicating moderate immune deficiency -- was above the World Health Organization's ART threshold of 200 cells/mm3 when the study began, but WHO raised this to 350 cells/mm3 in 2009. They were stratified by CD4 count below or above 50 cells/mm3. The median baseline CD4 count was 77 cells/mm3.
received standard rifampicin-containing TB treatment and trimethoprim/sulfamethoxazole
(TMP/SMX) prophylaxis. In addition, they were randomly assigned (1:1)
to start HIV therapy consisting of efavirenz (Sustiva) plus tenofovir/emtricitabine
(Truvada), either within 2 weeks (median 10 days) or within 8-12 weeks
(median 10 weeks) after starting TB treatment.
Based on these findings, the researchers concluded, "Overall, immediate ART did not reduce AIDS and death compared to early ART."
But they continued, "For persons with CD4 [counts] < 50 cells/mm3 immediate ART resulted in lower rates of AIDS and death compared to early ART."
was really a dramatic reduction, and it's very urgent that antiretroviral
therapy be started in this population," Havlir said at a CROI press
conference. "We absolutely need to act on this data. This study
shows that minutes matter if you have low CD4 counts."
In a second presentation, however, Salim Abdool Karim and fellow investigators with the CAPRISA 003 SAPiT trial sounded a note of caution regarding HIV/TB patients with better-preserved immune function.
study included more than 600 HIV positive participants starting TB treatment
in Durban, South Africa. The SAPIT enrollees had less advanced HIV disease
as a group, with a median baseline CD4 count of 150 cells/mm3 -- about
double that of the STRIDE participants.
"In patients with pulmonary TB/HIV coinfection with CD4 counts < 50 cells/mm3, early ART initiation within 4 weeks of TB treatment initiation was associated with better AIDS-free survival, albeit with increased risk of IRIS," the investigators concluded.
However, they added, "in patients with CD4 [counts] > 50 cells/mm3, delaying initiation of ART to the first 4 weeks of continuation phase of TB reduced the risk of IRIS and drug switches without compromising AIDS-free survival."
"Those with severe immune deficiency should start antiretroviral therapy ASAP," Abdool Karim said at the press conference. But if CD4 count is greater than 50 cells/mm3, "physicians can make a judgment" about whether the benefits of early ART outweigh the risks.
D Havlir, P Ive, M Kendall, and others. International Randomized Trial of Immediate vs Early ART in HIV+ Patients Treated for TB: ACTG 5221 STRIDE Study. 18th Conference on Retroviruses and Opportunistic Infections. Boston. February 27-March 2, 2011. Abstract 38.
Karim, K Naidoo, N Padayatchi, and others. Optimal Timing of ART during
TB Therapy: Findings of the SAPiT Trial. 18th Conference on Retroviruses
and Opportunistic Infections. Boston. February 27-March 2, 2011. Abstract