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Immediate Antiretrovirals During Acute OI Lower Death Risk: ACTG A5164
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15th Conference on Retroviruses and Opportunistic Infections
February 3-6, 2008
Boston
Mark Mascolini
Starting antiretrovirals immediately in a person with an acute opportunistic infection (OI) lowered the risk of AIDS progression and death compared with delaying antiretrovirals until OI drugs controlled the acute illness, according to results of ACTG A5164, a 282-person randomized trial [1]. Immediately treated people boosted their CD4s above 50 and 100 significantly faster than people in the deferred-antiretroviral group.
Because controversy persists over whether to start antiretrovirals straightaway in untreated people with an acute OI, Andrew Zolopa (Stanford University) and colleagues randomized 141 people with an acute OI or bacterial infection to start antiretrovirals as soon as they enrolled in the trial and 141 to defer treatment until at least 28 days after enrollment. Everyone began drugs for the OIs included in the trial--Pneumocystis pneumonia, bacterial pneumonia, cryptococcosis, Mycobacterium avium complex, or central nervous system toxoplasmosis.
The trial excluded anyone in whom antiretrovirals had failed and anyone who had taken antiretrovirals in the past 8 weeks or for more than 31 days in the past 6 months. The ACTG provided lopinavir/ritonavir, tenofovir/emtricitabine, and d4T, but clinicians could use any antiretrovirals and assumed responsibility for antiretroviral management.
ACTG A5164 had three primary endpoints:
· AIDS progression or death
· No progression, viral load above 50 copies
· No progression, viral load below 50 copies
The study group was 85% male, 36% black, and 36% Hispanic. Median age stood at 38 years, and 87% of enrollees had never injected illicit drugs. Median baseline viral load measured 5.07 log (just over 100,000 copies) and median CD4 count 29 cells (interquartile range 10 to 55). A large majority of enrollees, 92%, had never taken antiretrovirals, and almost two thirds had Pneumocystis pneumonia. Over 80% in both the immediate and deferred antiretroviral groups started a PI.
After 48 weeks Zolopa and colleagues found no significant differences between groups in any of the three primary endpoints. But 34 people (24.1%) in the deferred group versus 20 (14.2%) in the immediate group had a new AIDS diagnosis or died, a significant difference (P = 0.035). That difference meant people who started antiretrovirals immediately had half the chance of progression as people who deferred (odds ratio 0.51, 99% confidence interval 0.23 to 1.15). Time to AIDS progression or death proved significantly faster in the deferred group (P = 0.023, hazard ratio 0.53, 99% confidence interval 0.26 to 1.09). And times to CD4 counts above 50 and 100 cells were significantly shorter in the immediate group (P < 0.001 for both CD4 counts).
Because immediate antiretrovirals drove CD4s up faster, Zolopa noted, people getting immediate therapy had a smaller "window of vulnerability" to new OIs or death. Death and progression rates in the two treatment arms diverged mainly in the first 6 months of follow-up. By trial week 48 the two groups did not differ in viral load.
Zolopa summarized the impact of immediate antiretroviral therapy in six points:
· Fewer cases of AIDS progression or death
· More rapid CD4 gains
· Equivalent virologic response by 48 weeks
· Requires more regimen changes
· No difference in safety
· No difference in incidence of immune reconstitution inflammatory syndrome (IRIS)
Based on these findings the ACTG recommends immediate antiretroviral therapy for people with an acute AIDS-related OI or bacterial infection unless there are major contraindications to treatment.
Reference
1. Zolopa A, Andersen J, Komarow I, et al. Immediate vs deferred ART in the setting of acute AIDS-related opportunistic infection: final results of a randomized strategy Trial, ACTG A5164. 15th Conference on Retroviruses and Opportunistic Infections. February 3-6, 2008. Boston. Abstract 142.
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