48 week data on  Ritonavir+Indinavir: reported at Abbott symposium in Lisbon

Pharmacokinetic Data (See Table 14):  

Table 14.

RTV+IDV

Dose

AUC

Cmax

Cmin

IDV 3x/day

800 mg

57

7.6

0.17

IDV 2x/day

1200 mg

66

13.1

0.08

2x/day RTV

100 mg/IDV 1200 mg

170

15.5

0.81

2x/day RTV

100 mg/IDV 800

84

8.8

0.82

2x/day RTV

400 mg + IDV 400 mg

51

4.3

0.83

Abbott feels the 400/400 dose regimen is preferable. Merck is researching 800/100 IDV/RTV and 800/200. A comparative study is needed.  

Jurgen Rockstrob from the University of Bonn in Germany reported 48-week data from an open-label uncontrolled multicenter study of 400+400 bid.  90 treatment nave patients with "high median" HIV RNA of 220,000 copies/ml (range 36,000 2.9 million) and a median CD4 count of 189 (range 4 676) were included. 49% of patients were started on concomitant AZT/3TC, 38% d4T/3TC and 13% on d4T/ddI in combination with 400+400 bid RTV/IDV.

Results.  The median viral load reduction was 3.5 log at week 48 (n=54). Using the on-treatment analysis, 95% had below 500 and 91% had below 80 copies/ml at week 24 (n=54). In the ITT (Intent to Treat) analysis, the percent with below 500 copies/ml and below 80 copies/ml at week 24 was 67% and 64%, respectively. Rockstrob said the ITT data at week 48 was hampered by 4 individuals not yet reaching 48 weeks and being counted as failures due to that and because during the study individuals had to temporarily switch to RTV liquid. At week 16, prior to switching to liquid about 85% had below 500 copies/ml and about 75% had below 80 copies/ml. Mean CD4 increase was about 190 from baseline.

The adverse event rate was 38%. The most common were nausea, diarrhea, peripheral parasthesia. There were elevations in cholesterol,  triglycerides and LFTs, Two people had transient elevation of amylase and lipase, 1 thrombocytopenia, 1 osteonecrosis. So far, no cases of kidney stones, no cases of flank pain, no elevation of serum creatinine.

Mean triglycerides increased from 132 at baseline to 304 (mg/dL) at week 48. Mean cholesterol increased from 179 at baseline to 251 (mg/dL) at week 48. Creatinine was 82 at baseline and 88 at week 48.

92 patients were enrolled. There were 24 discontinuations: 6 due to adverse events (1 LFTs, 3 nausea, 2 diarrhea) 1 death, 4 lost to follow-up, 11 for non-compliance with RTV liquid and 2 other.