The role of abacavir (ABC, 1592) in antiretroviral therapy-experienced patients: results from a randomized, double-blind, trial. CNA3002 European Study Team.
OBJECTIVE
To compare the antiviral activity of abacavir (ABC) with stable background therapy (SBG) and SBG alone in antiretroviral therapy-experienced subjects as demonstrated by the proportion of subjects with plasma HIV-1 RNA < or = 400 copies/ml, plasma HIV-1 RNA and CD4 cell count profiles, and safety and tolerance of the two regimens over 16 weeks.


METHODS
One-hundred and eighty-five HIV-1 infected adults, with CD4 cell counts > or = 100 x 10(6)/l and plasma HIV-1 RNA of 400-50,000 copies/ml and who had received SBG therapy for at least 12 weeks, were randomized to receive ABC (300 mg twice daily) or placebo in a double blind, multi-centre study.


METHODS
Antiretroviral activity was assessed by measuring changes in plasma HIV-1 RNA levels and CD4 cell counts. Genotypic and phenotypic resistance was determined at baseline and week 16. Evaluation of safety and tolerance was based on clinical adverse events and laboratory analyses.


RESULTS
At week 16 significantly more subjects receiving ABC + SBG had plasma HIV-1 RNA < or = 400 copies/ml (36/92, 39%) than subjects receiving SBG alone (7/93, 8%; P < 0.001). A similar response was observed in both the lamivudine naive and lamivudine-experienced subjects. The presence of the M184V mutation did not preclude an antiviral response to ABC; 73% of subjects with the M184V mutation alone experienced a > or = 1.0 log10 copies/ml reduction in plasma HIV-1 RNA or had a value of < or = 400 copies/ml by week 16.


CONCLUSIONS
ABC was generally well tolerated and exerted significant antiviral effect when added to combination antiretroviral therapy over 16 weeks.
Katlama
C
C
Hopital de la Pitie Salpetriere, Paris, France.
Clotet
B
B
Plettenberg
A
A
Jost
J
J
Arasteh
K
K
Bernasconi
E
E
Jeantils
V
V
Cutrell
A
A
Stone
C
C
Ait-Khaled
M
M
Purdon
S
S
D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015224:Dideoxynucleosides / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D004311:Double-Blind Method; D004352:Drug Resistance, Microbial; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load; D000099227:Abacavir
D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D054303:HIV Reverse Transcriptase; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D000099227:Abacavir