DIRECT Study: 800/100 mg Indinavir-Ritonavir BID +abacavir/3TC

We saw at Durban a number of studies reporting relatively longer-term data on various dosing combinations of IDV-RTV double PI regimens (400-400, 800-100, 800-200). At ICAAC M Watkins reported preliminary data from the DIRECT Study, which is a small multi-center, open-label 24 week pilot study with a 24-week extension. The study is a single-arm non-comparative trial of 800/100 mg bid of indinavir & ritonavir with 3TC and abacavir in treatment naÔve patients.

Although 89 HIV-infected patients were enrolled, only 80 were available for analysis because 9 were excluded for incomplete data a the time of analysis. There were 80% men, 48% caucasian (31% African-American, 20% Hispanic), and 11% with AIDS defining illnesses. Of 80 patients in analysis, mean CD4 was 275 and viral load 5.01 log (102,000 copies/ml).

At week 24, 50 patients were continuing in study, which is 60% of 80 and 56% of 89. 16 patients discontinued (18% of 89). Reasons for discontinuation: clinical adverse event n=8 9%), HIV increase 0, Lab adverse event 0, Lost to follow-up 1, other (mover; heroin withdrawal).

Clinical Adverse Events Summary

6 (6.7%) of patients discontinued due to drug related AE. 10 reportedly had serious AE, 3 had drug related AE and 2 discontinued due to drug related AE.

NEPHROLITHIASIS

15 patients had neprholithiasis (15/89 16.9%). Nephrolithiasis was defined as flank pain, with or without hematuria or urolithiasis. 3/89 discontinued (3.3%). 10/15 patients continued on therapy without interruption, 2/15 patients temporarily interrupted therapy. 3/15 discontinued due to nephrolithiasis.

Analysis of the incidence of nephrolithiasis in a study is subject to a number of variables that are not easy to sort out. The patient's adherence to adequate hydration is never monitored and it's obviously very difficult to do that. In warm climates or when it is hot, hydration requirements may be increased but you don't know if patients are adhering to that. The study site for this trial were listed as Philadelphia, Miami, San Francisco and Denver. In the Summer in New York City it can be very hot and hydration requirements may have to be increased.

VIRAL SUPPRESSION

Investigators said they used the observed data analysis because this is a preliminary analysis and not all patients have reached week 24.

Watkins is tracking fasting lipids. Visual observation of graph on poster showed at baseline tryglicerides were about 100 and cholesterol 150 mg/dL (n=19). At week 24 (n=20) fasting triglycerides were about 150 and cholesterol about 210.

Lab Adverse Events

26 (32%) patients had lab AE: 2 elevated triglycerides, 7 elevated cholesterol, 2 elevated glucose, 4 elevated ALT, 16 elevated total serum bilirubin, 11 increased indirect serum bilirubin.