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August, 2006 Literature Review CD4-guided structured antiretroviral treatment interruption strategy in HIV-infected adults in west Africa (Trivacan ANRS 1269 trial): a randomized trial Summary: The Trivacan 1269 trial is an ANRS trial done in Cote d'Ivoire to determine the efficacy of structured treatment interruption. Methods: All patients had continuous antiretroviral therapy for 6-18 months using either AZT/3TC combined with either EFV or IDV/r (800/100 twice daily). There were 651 participants randomized to one of three arms: 1) continuous treatment (110 participants); 2) CD4 guided treatment (216 participants) or 3) four months-on then two months-off (325 participants). Group 3 was not presented and will not be discussed further. For the CD4 guided group, treatment was suspended when the CD4 count exceed 350 cells/mm3 and was restarted when the CD4 count decreased below 250 cells/mm3. Results: The study was discontinued for the CD4-guided groups after a median follow-up of 20 months. At this time, there was not a significant difference between the two groups for mortality, but there was a statistically significant increase in "severe morbidity" in the CD4 guided treatment group with 17.6 events/100 person-years compared to 6.7/100 person-years in the control group. The most frequent severe events were bacterial infections including E. coli, salmonella and S. pneumoniae as the dominant pathogens. Infections involving these three organisms totaled one in the continuous treatment arm and 28 in the CD4 cell guided group. These results are summarized in the following table:
Conclusion: The authors conclude that the CD4 guided treatment interruption was associated with morbidity rates that were 2.5 fold higher compared to continuous treatment. This difference was attributed to high rates of common diseases in patients with CD4 counts of 200-500 cells/mm3. Commentary: This was one of the major papers presented at the 2005 CROI having negative results for CD4 cell guided treatment interruption. The other was the SMART trial. Both concluded that this therapeutic tactic should not be used, but the reasons were somewhat different. Both showed excessive rates of morbidity, but the Trivacan trial showed most of the difference could be attributed to severe bacterial infections; by contrast, the SMART trial showed high rates of "events", but many were attributed to adverse drug reactions, opportunistic infections and death. Both studies have been criticized for the trial design in which the CD4 cell guided strategy was to discontinue treatment when the CD4 count was above 350 cells/mm3 and restart when it decreased below 250 cells/mm3; many others who are doing these trials have used more conservative thresholds, generally restarting treatment when the CD4 count was below 350 cells/mm3. Nevertheless, these two studies have clearly dampened enthusiasm for CD4 cell guided treatment interruption which is now considered "experimental". Literature Review by John G. Barlett, M.D. Professor, Division of Infectious Diseases |
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