Virologic response and safety of the abacavir/lamivudine fixed-dose formulation as part of highly active antiretroviral therapy: analyses of six clinical studies.
OBJECTIVE
We analyzed virologic response and safety data from six recent clinical studies conducted in antiretroviral-naïve subjects treated with ABC/3TC or its components to assess the impact of baseline viral load on efficacy and safety endpoints used in the ACTG5202 protocol.


METHODS
Primary endpoints were time to virologic failure (confirmed HIV-1 RNA > or = 1,000 copies/mL at 16-24 weeks or > or = 200 copies/mL at > or = 24 weeks) and time to first grade 3 or 4 adverse event or laboratory abnormality that was at least one grade higher than at baseline. The survival distributions of both endpoints were estimated using the Kaplan-Meier method overall and by baseline viral load (<100,000 vs. 100,000 copies/mL). A weighted mean of the virologic response and 95% confidence intervals (CI) were calculated by inverse-variance weighting for baseline viral load 100,000 copies/mL across studies.


RESULTS
For subjects with baseline HIV-1 RNA 100,000 copies/mL, the rate of virologic survival ranged from 87% to 95% by 48 weeks. Few subjects treated with ABC/3TC developed grade 3 or 4 adverse events, laboratory toxicities, or changes in lipid levels. The weighted mean (CI) for the pooled virologic response was 91% (87%-96%).


CONCLUSIONS
Based on the A5202 endpoints, ABC/3TC-containing regimens in this analysis had a high rate of virologic survival and were generally well tolerated in antiretroviral-naïve subjects regardless of baseline viral load. The pooled virologic response for ABC/3TC in our analysis is higher than the A5202 estimate.
Ha
Belinda
B
GlaxoSmithKline, Research Triangle Park, North Carolina, USA. Belinda.f.ha@gsk.com
Liao
Qiming M
QM
Dix
Lynn P
LP
Pappa
Keith A
KA
D000293:Adolescent; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000592:standards; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods / Q000592:standards*; D002219:Carbamates / Q000494:pharmacology; D002986:Clinical Trials as Topic; D015224:Dideoxynucleosides; D004338:Drug Combinations; D005260:Female; D005663:Furans; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D019259:Lamivudine / Q000494:pharmacology* / Q000592:standards; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D010755:Organophosphates / Q000494:pharmacology; D011744:Pyrimidinones / Q000494:pharmacology; D012367:RNA, Viral / Q000097:blood; D016032:Randomized Controlled Trials as Topic; D013449:Sulfonamides / Q000494:pharmacology; D016019:Survival Analysis; D019562:Viral Load; D055815:Young Adult; D000099227:Abacavir
D019380:Anti-HIV Agents; D002219:Carbamates; D015224:Dideoxynucleosides; D004338:Drug Combinations; D005663:Furans; D019259:Lamivudine; D061466:Lopinavir; D010755:Organophosphates; D011744:Pyrimidinones; D012367:RNA, Viral; D013449:Sulfonamides; C492871:abacavir, lamivudine drug combination; D000099227:Abacavir; C426859:fosamprenavir