Combined therapy with saquinavir, ritonavir and stavudine in moderately to severely immunosuppressed HIV-infected protease inhibitor-naive patients.
OBJECTIVE
To assess the short-term and long-term effect of a combination of saquinavir, ritonavir and stavudine in moderately to severely immunosuppressed protease inhibitor-naive patients.


METHODS
Prospective open-label multicentre study.


METHODS
A total of 64 protease inhibitor-naive and stavudine-naive HIV-infected patients with a CD4 count of < 250 cells/microL and > 10 000 HIV-1 RNA copies/mL received saquinavir hard-gelatin capsules, ritonavir and stavudine. Full (drop in viraemia of > 2 log10 and/or < 500 copies/mL) and partial responders (drop to between 500 and 5000 viraemia copies/mL) at week 9 (end of phase I) entered the second phase (additional 12-month period).


RESULTS
Fifty-six patients completed phase I, 45 (70%) full responders and nine (14%) partial responders by intent-to-treat analysis. Thirty-nine patients completed phase II, 33 (52%) full responders and two (3%) partial responders. Six patients had < 50 HIV-1 RNA copies/mL at week 9, and 20 (31%) patients at month 12 of phase II. Mean CD4 cell counts increased significantly in the 56 patients from 89 to 184 cells/microL after 9 weeks and from 100 to 292 cells/microL in the 39 patients treated for another 12 months. Higher baseline viraemia and lower baseline CD4 cell counts were not associated with an unfavourable virological response at week 9 and month 12 of phase II. HIV DNA in peripheral blood monocytes decreased substantially (- 1.5 log10) but was detectable in all except one patient at the end of phase II.


CONCLUSIONS
In protease- and stavudine-naive HIV-infected patients with moderate to severe immunosuppression, saquinavir in combination with ritonavir and stavudine caused a substantial long-term decrease in plasma viral load in approximately half the participants and a substantial increase in CD4 cell counts.
Battegay
M
M
Basel Centre for HIV Research, Outpatient Department of Internal Medicine, University Hospital Basel, Switzerland. mbattegay@uhbs.ch
Vernazza
P L
PL
Bernasconi
E
E
Flepp
M
M
Sendi
P
P
Erb
P
P
Malinverni
R
R
Jaccard
C
C
Morgenthaler
S
S
Bedoucha
V
V
Hirschel
B
B
D000293:Adolescent; D000328:Adult; D000368:Aged; D015331:Cohort Studies; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D016867:Immunocompromised Host; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D019438:Ritonavir / Q000008:administration & dosage / Q000627:therapeutic use*; D019258:Saquinavir / Q000008:administration & dosage / Q000627:therapeutic use*; D018119:Stavudine / Q000008:administration & dosage / Q000627:therapeutic use*; D013557:Switzerland; D016896:Treatment Outcome; D019562:Viral Load
D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D018119:Stavudine; D019258:Saquinavir; D019438:Ritonavir