Activity of the soft gelatin formulation of saquinavir in combination therapy in antiretroviral-naive patients. NV15355 Study Team.
OBJECTIVE
A Phase II, open-label, randomized, parallel-arm, multicentre trial to compare the antiviral activity and safety of two formulations of saquinavir (SQV), soft gelatin (SQV-SGC) and hard gelatin (SQV-HGC) capsules, in combination with two nucleoside reverse transcriptase inhibitors (NRTI), in antiretroviral-naive, HIV-1-infected individuals.


METHODS
A total of 171 people of > or = 13 years, with plasma HIV-1 RNA levels > or = 5000 copies/ml, who had received no protease inhibitor therapy, < or = 4 weeks NRTI therapy and no antiretroviral treatment within 28 days of screening. Eighty-one people were randomized to the SQV-HGC group and 90 to the SQV-SGC group. A total of 148 patients completed 16 weeks of therapy.


METHODS
Therapy for 16 weeks with either SQV-SGC 1200 mg or SQV-HGC 600 mg, both three times a day, in combination with two NRTI.


RESULTS
Using an on-treatment analysis, patients taking SQV-SGC had a larger reduction in plasma HIV-1 RNA than those taking SQV-HGC (-2.0 versus -1.6 log10 copies/ml). Eighty per cent of those on SQV-SGC had < 400 copies HIV RNA/ml, compared with 43% in the SQV-HGC group (P = 0.001). A statistically significant difference in the area under the curve (AUC) values between the SQV-SGC and SQV-HGC arms (-1.7 versus -1.5 log10 copies/ml, respectively; P = 0.0054) was observed when withdrawals prior to week 12, major protocol violators and patients with < 75% compliance were excluded from the analysis; however, the difference between the values for the intent-to-treat population was not significant (P = 0.1929). Adverse events (mostly mild) included diarrhoea and nausea.


CONCLUSIONS
SQV-SGC was generally well tolerated and gave significantly more potent suppression of plasma HIV-1 RNA in antiretroviral-naive patients than SQVHGC.
Mitsuyasu
R T
RT
University of California, Los Angeles, USA.
Skolnik
P R
PR
Cohen
S R
SR
Conway
B
B
Gill
M J
MJ
Jensen
P C
PC
Pulvirenti
J J
JJ
Slater
L N
LN
Schooley
R T
RT
Thompson
M A
MA
Torres
R A
RA
Tsoukas
C M
CM
D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D002626:Chemistry, Pharmaceutical; D003257:Consumer Product Safety; D004359:Drug Therapy, Combination; D005260:Female; D005780:Gelatin; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood; D019258:Saquinavir / Q000008:administration & dosage / Q000627:therapeutic use*
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D005780:Gelatin; D019258:Saquinavir