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Induction Then Maintenance Therapy Ineffective for HIV Infection

Since HIV antiretroviral drugs are expensive, require many doses per day, and frequently cause side effects, investigators are looking hard for more user-friendly regimens. One strategy of great interest is intensive induction followed by a simpler maintenance schedule. However, this strategy has been unsuccessful in two recent trials.

In an ACTG study, both zidovudine-naive and zidovudine-experienced patients received 6 months of zidovudine (ZDV), lamivudine (LMV), and indinavir (IND). The 309 patients whose HIV RNA levels were suppressed to below 200 copies/ml were then randomized to receive ZDV + LMV or IND or to continue the induction regimen. After a median follow-up of 8 weeks, significantly fewer patients had lost viral suppression in the triple-therapy arm (4%), compared with the dual-therapy (23%, p<0.001) and monotherapy (23%, p<0.001) arms.

In a French study, ZDV-naive patients received ZDV + LMV + IND for 3 months. The 279 whose HIV RNA levels dropped to below 500 copies/ml were then randomized to receive ZDV + LMV, ZDV + IND, or the continued induction regimen. After a median follow-up of 24 weeks, significantly fewer relapses had occurred in the triple-therapy arm (9%), compared with the ZDV + LMV (31%, p<0.001) and the ZDV + IND (22%, p<0.01) arms.

Comment: Although these two trials differed in regard to the populations studied, duration of induction, and drug combinations used during the maintenance phase, the conclusions were similar: Only the induction regimen successfully contained HIV infection. The concept of a simplified maintenance regimen is appealing but apparently entails a substantial risk of viral rebound. Since details of viral resistance in recurrences and whether patients were successfully reinduced were not given, it is difficult to evaluate the long-term significance of viral rebound with the use of an induction-maintenance strategy. Nevertheless, for the present, clinicians and patients should avoid this strategy.

— R Horsburgh

Published in Journal Watch Infectious Diseases December 1, 1998

Citation(s):

Havlir DV et al. Maintenance antiretroviral therapies in HIV-infected subjects with undetectable plasma HIV RNA after triple-drug therapy. N Engl J Med 1998 Oct 29; 339:1261-8.

• Original article (Subscription may be required)
• Medline abstract (Free)

Pialoux G et al. A randomized trial of three maintenance regimens given after three months of induction therapy with zidovudine, lamivudine, and indinavir in previously untreated HIV-1 infected patients. N Engl J Med 1998 Oct 29; 339:1269-76.

• Original article (Subscription may be required)
• Medline abstract (Free)