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Alternation
of Antiretroviral Drug Regimens for HIV Infection: Efficacy, Safety
and Tolerability at Week 96 of the Swatch Study
Alternation
of antiretroviral drug regimens has been proposed
as a novel treatment strategy for HIV infection. However, some concerns
persist regarding antiviral efficacy, adherence,
toxicity
and resistance
evolution in the long term.
Methods
A
total of 161 antiretroviral-naive HIV-1-infected patients were randomized
to receive stavudine/didanosine/efavirenz
(group A) or zidovudine/lamivudine/
nelfinavir
(group B) or to alternate between the two regimens every 3 months
starting with regimen A (group C). Antiviral efficacy, adherence,
safety and tolerability were analyzed every 12 weeks.
Results
After
96 weeks, time to virological
failure was significantly delayed in the alternating
regimen compared with the standards of care regimens. Virological
suppression was seen in 46%, 48% and 58% of patients
in groups A, B and C, respectively, in the intention-to-treat analysis
and in 75%, 76% and 97% in the on-treatment analysis (A vs C: P=0.014;
B vs C: P=0.016; A vs B: P=0.849).
At
the end of the study, 94% of patients in group A and 92% in groups
B and C reported an adherence greater than 95%. Alternating therapy
was associated with a similar impact on CD4+
counts in comparison with the standards of care regimens,
as well as a lower mitochondrial
DNA/nuclear DNA (mtDNA/nDNA) ratio decrease in the
mitochondrial substudy performed on 37 patients.
The
frequency and intensity of adverse
events in the alternating group decreased during
subsequent cycles.
Discussion
Our
results favor the hypothesis that proactive therapy switching may
delay the accumulation of resistance mutations. Moreover, the alternating
regimen was well tolerated and adherence remained comparably high
in all treatment groups. The lower mtDNA/nDNA ratio decrease observed
in this group may imply a lower impact on mitochondrial
toxicity than in standard regimens.
Department
of Internal Medicine, Lluita contra la SIDA and IrsiCaixa Foundations,
Hospital Universitari Germans Trias i Pujol, Barcelona, Spain.
1/26/05
Reference
E
Negredo and others (the Swatch Study Team). Alternation of
antiretroviral drug regimens for HIV infection. Efficacy, safety
and tolerability at week 96 of the Swatch Study. Antiviral
Therapy 9(6): 889-893. December
2004.
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