Treatment intensification with abacavir in HIV-infected patients with at least 12 weeks previous lamivudine/zidovudine treatment.
OBJECTIVE
To demonstrate that lamivudine and zidovudine, given separately (lamivudine/zidovudine) or as a single combination tablet (Combivir), had equivalent efficacy. To evaluate the safety and antiretroviral activity of intensification with abacavir in patients treated with lamivudine/zidovudine for > or = 12 weeks.


METHODS
A 12-week, equivalence study of lamivudine/ zidovudine versus Combivir. Patients who completed this study could enter a 48-week, intensification study of Combivir plus abacavir.


METHODS
In the equivalence study, treatment-naive patients were assessed for HIV-1 RNA, CD4 cell count and genotype. The same assessments plus phenotype were made in the intensification study. Serious adverse events were recorded in the equivalence study and all adverse events in the intensification study.


RESULTS
Lamivudine/zidovudine (n=40) and Combivir (n=35) gave equivalent reductions in plasma HIV-1 RNA levels at week 12. An identical proportion of patients (74%) in each treatment group harboured virus with the M184V mutation after 12 weeks. Fifty-two patients entered the intensification study and 44 completed 48 weeks of treatment. At the time of intensification with abacavir, all 35 patients with evaluable isolates harboured HIV-1 containing M184V. Addition of abacavir to Combivir led to further decreases in plasma HIV-1 RNA and increases in CD4 cell counts compared with the start of intensification (P<0.001 at week 48). After 48 weeks of triple therapy, multi-nucleoside resistance mutations at codons 69 and 151 were not detected in any patients. All treatment regimens were generally well tolerated.


CONCLUSIONS
Lamivudine/zidovudine and Combivir have equivalent antiretroviral activity over 12 weeks. Adding abacavir to Combivir can be a safe and effective therapeutic option for patients, including those harbouring virus with the M184V mutation.
Rozenbaum
W
W
Maladies Infectieuses Trĵpicales, Hĵpital Rothschild, Paris, France. willy.rozenbaum@rth.ap-hop-paris.fr
Katlama
C
C
Massip
P
P
Bentata
M
M
Zucman
D
D
Delfraissy
J F
JF
Trepo
C
C
David
F
F
Lanier
E R
ER
Vavro
C
C
Mamet
J P
JP
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D015224:Dideoxynucleosides / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D013997:Time Factors; D015215:Zidovudine / Q000008:administration & dosage*; D000099227:Abacavir
D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D004338:Drug Combinations; D019259:Lamivudine; D012367:RNA, Viral; D015215:Zidovudine; D000099227:Abacavir