Alternation of antiretroviral drug regimens for HIV infection. Efficacy, safety and tolerability at week 96 of the Swatch Study.
BACKGROUND
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 analysed 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.


CONCLUSIONS
Our results favour 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.
Negredo
Eugenia
E
Department of Internal Medicine, Lluita contra la SIDA and IrsiCaixa Foundations, Hospital Universitari Germans Trias i Pujol, Barcelona, Spain. enegredo@h0600.hugtip.scs.es
Paredes
Roger
R
Peraire
Joaquim
J
Pedrol
Enric
E
Côté
Helene
H
Gel
Silvia
S
Fumoz
Carmina R
CR
Ruiz
Lidia
L
Abril
Vicente
V
Rodriguez de Castro
Eduardo
E
Ochoa
Claudia
C
Martinez-Picado
Javier
J
Montaner
Julio
J
Rey-Joly
Celestino
C
Clotet
Bonaventura
B
D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D010349:Patient Compliance; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors