Predictors of optimal viral suppression in patients switched to abacavir, lamivudine, and zidovudine: the Swiss HIV Cohort Study.
OBJECTIVE
To investigate predictors of continued HIV RNA viral load suppression in individuals switched to abacavir (ABC), lamivudine (3TC) and zidovudine (ZDV) after successful previous treatment with a protease inhibitor or non-nucleoside reverse transcriptase inhibitor-based combination antiretroviral therapy.


METHODS
An observational cohort study, which included individuals in the Swiss HIV Cohort Study switching to ABC/3TC/ZDV following successful suppression of viral load. The primary endpoint was time to treatment failure defined as the first of the following events: two consecutiveviral load measurements > 400 copies/ml under ABC/3TC/ZDV, one viral load measurement > 400 copies/ml and subsequent discontinuation of ABC/3TC/ZDV within 3 months, AIDS or death.


RESULTS
We included 495 individuals; 47 experienced treatment failure in 1459 person-years of follow-up [rate = 3.22 events/100 person-years; 95% confidence interval (95% CI), 2.30-4.14]. Of all failures, 62% occurred in the first year after switching to ABC/3TC/ZDV. In a Cox regression analysis, treatment failure was independently associated with earlier exposure to nucleoside reverse transcriptase inhibitor (NRTI) mono or dual therapy [hazard ratio (HR), 8.02; 95% CI, 4.19-15.35) and low CD4 cell count at the time of the switch (HR, 0.66; 95% CI, 0.51-0.87 by +100 cells/microl up to 500 cells/microl). In patients without earlier exposure to mono or dual therapy, AIDS prior to switch to simplified maintenance therapy was an additional risk factor.


CONCLUSIONS
The failure rate was low in patients with suppressed viral load and switch to ABC/3TC/ZDV treatment. Patients with earlier exposure to mono or dual NRTI therapy, low CD4 cell count at time of switch, or AIDS are at increased risk of treatment failure, limiting the use of ABC/3TC/ZDV in these patient groups.
Wolbers
Marcel
M
Basel Institute for Clinical Epidemiology, University Hospital Basel, Switzerland.
Opravil
Milos
M
von Wyl
Viktor
V
Hirschel
Bernard
B
Furrer
Hansjakob
H
Cavassini
Matthias
M
Vernazza
Pietro
P
Bernasconi
Enos
E
Battegay
Manuel
M
Yerly
Sabine
S
Günthard
Huldrych
H
Bucher
Heiner C
HC
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D015224:Dideoxynucleosides / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D019450:Genes, MDR; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D016016:Proportional Hazards Models; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D013557:Switzerland; D017211:Treatment Failure; D019562:Viral Load; D015215:Zidovudine / Q000627:therapeutic use*; D000099227:Abacavir
D015224:Dideoxynucleosides; D017320:HIV Protease Inhibitors; D019259:Lamivudine; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D000099227:Abacavir