A comparison of stavudine, didanosine and indinavir with zidovudine, lamivudine and indinavir for the initial treatment of HIV-1 infected individuals: selection of thymidine analog regimen therapy (START II).
OBJECTIVE
Comparison of stavudine (d4T), didanosine (ddI) and indinavir (IDV) with zidovudine (ZDV), lamivudine (3TC) and IDV in HIV-1 infected patients.


METHODS
Randomized, open-label.


METHODS
Fourteen HIV Clinical Research Centers.


METHODS
Two-hundred and five patients with less than 4 weeks antiretroviral treatment, naive to 3TC and protease inhibitors and with CD4 cell counts > or = 200 x 10(6)/l and plasma HIV-1 RNA levels > or = 10,000 copies/ml.


METHODS
Stavudine 40 mg and ddI 200 mg twice daily plus IDV 800 mg every 8 h compared with ZDV 200 mg every 8 h or 300 mg twice daily, 3TC 150 mg twice daily plus IDV.


METHODS
The proportion of patients with plasma HIV-1 RNA levels < 500 copies/ml and < or = 50 copies/ml and changes in CD4 cell counts were compared.


RESULTS
In an analysis of the primary endpoint, 61% of patients on d4T + ddI + IDV and 45% of patients on ZDV + 3TC + IDV had all HIV-1 RNA values obtained between weeks 40 and 48 < 500 copies/ml [95% confidence interval (CI) for the difference between proportions, 1.7-30.3%; P = 0.038]. In an intent-to-treat analysis, the percentage of all patients randomized with all HIV-1 RNA levels < 500 copies/ml between 40 and 48 weeks were 53% for the d4T + ddI + IDV arm and 41% for the ZDV + 3TC + IDV arm (95% CI, -1.4% to 25.7%; P = 0.068). At 48 weeks 41% and 35% were < or = 50 copies/ml for the stavudine- and ZDV-containing arms respectively (P > 0.2). The median time-weighted average increases in CD4 cells count over 48 weeks were 150 x 10(6)/l cells for the d4T arm and 106 x 10(6)/l cells for the ZDV arm (P= 0.001). The occurrence of serious adverse events was not significantly different between arms.


CONCLUSIONS
The combination of stavudine, ddl and IDV resulted in potent antiretroviral effects over a 48-week period, comparable or superior to zidovudine, 3TC and IDV supporting the use of stavudine, ddI and a protease inhibitor as an initial antiretroviral treatment.
Eron
J J
JJ
University of North Carolina School of Medicine, Chapel Hill 27599-7030, USA.
Murphy
R L
RL
Peterson
D
D
Pottage
J
J
Parenti
D M
DM
Jemsek
J
J
Swindells
S
S
Sepulveda
G
G
Bellos
N
N
Rashbaum
B C
BC
Esinhart
J
J
Schoellkopf
N
N
Grosso
R
R
Stevens
M
M
D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D016049:Didanosine / Q000009:adverse effects / Q000627:therapeutic use; D015224:Dideoxynucleosides / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D015497:HIV-1; D006801:Humans; D019469:Indinavir / Q000009:adverse effects / Q000627:therapeutic use*; D019259:Lamivudine / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D018119:Stavudine / Q000009:adverse effects / Q000627:therapeutic use; D013936:Thymidine / Q000031:analogs & derivatives; D019562:Viral Load; D015215:Zidovudine / Q000009:adverse effects / Q000627:therapeutic use
D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D015215:Zidovudine; D019469:Indinavir; D018119:Stavudine; D016049:Didanosine; D013936:Thymidine