Alternation of antiretroviral drug regimens for HIV infection.  A randomized, controlled trial. 
Mathematical modeling has suggested that alternating antiretroviral regimens while patients' viral load remains suppressed would minimize HIV resistance mutations.  To compare alternation of antiretroviral regimens with the current standard of switching regimens after viral load rebound.  Randomized, multicenter, open-label, pilot trial.  15 outpatient HIV clinics in Spain and Argentina.  161 HIV-1-infected, antiretroviral-naive persons.  Patients were assigned to continuously receive stavudine, didanosine, and efavirenz (standard of care, regimen A) or zidovudine, lamivudine, and nelfinavir (standard of care, regimen B) until virologic failure, or to alternate between those two regimens every 3 months while viral load was suppressed (regimen C).  Time to virologic failure, percentage of patients with undetectable plasma viremia over 48 weeks, CD4 and CD8 cell counts, adverse events, emergence of drug resistance, drug adherence, and quality of life.  Patients receiving standard-of-care regimens A and B did not differ.  Virologic failure over 48 weeks was delayed in the alternating therapy group compared with the pooled standard-of-care group (incidence rate, 1.2 events/1000 person-weeks [95% CI, 0.3 to 3.6 events/1000 person-weeks] vs. 4.8 events/1000 person-weeks [CI, 2.9 to 7.4 events/1000 person-weeks]; P = 0.01).  Genotypic drug resistance emerged in 79% of patients in the standard-of-care group who experienced on-therapy treatment failure.  Patients in the standard-of-care and alternating therapy groups had similar CD4 cell counts, frequency of adverse events, reported drug adherence, and quality of life.  Virologic outcome was better with alternating therapy than with the current standard of care, while adverse events and adherence were similar.  The strategy of alternating therapy merits further investigation.