Alternation of antiretroviral drug regimens for HIV infection. A randomized, controlled trial.
BACKGROUND
Mathematical modeling has suggested that alternating antiretroviral regimens while patients' viral load remains suppressed would minimize HIV resistance mutations.


OBJECTIVE
To compare alternation of antiretroviral regimens with the current standard of switching regimens after viral load rebound.


METHODS
Randomized, multicenter, open-label, pilot trial.


METHODS
15 outpatient HIV clinics in Spain and Argentina.


METHODS
161 HIV-1-infected, antiretroviral-naive persons.


METHODS
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).


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Martinez-Picado
Javier
J
IrsiCaixa Foundation, Hospital Germans Trias i Pujol, Carretera de Canyet s/n, 08916 Badalona, Spain. javiermp@ns.hugtip.scs.es
Negredo
Eugènia
E
Ruiz
Lidia
L
Shintani
Ayumi
A
Fumaz
Carmina R
CR
Zala
Carlos
C
Domingo
Pere
P
Vilaró
Josep
J
Llibre
Josep M
JM
Viciana
Pompeyo
P
Hertogs
Kurt
K
Boucher
Charles
C
D'Aquila
Richard T
RT
Clotet
Bonaventura
B
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000821:virology; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects / Q000379:methods*; D018791:CD4 Lymphocyte Count; D016516:CD4-CD8 Ratio; D018450:Disease Progression; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral; D005260:Female; D006801:Humans; D008297:Male; D010349:Patient Compliance; D010865:Pilot Projects; D011788:Quality of Life; D017211:Treatment Failure; D019562:Viral Load