Daily Highlight Report 2 from Lisbon – 7th European AIDS Conference

Jules Levin, NATAP

This is Jules Levin reporting from Lisbon after day 2 of the pre-conference satellite symposiums. Yesterday’s Report 1 contained a 48 week update of RTV+IDV 400mg+400mg bid study with pharmacokinetics of RTV+IDV. This report contains presentation today at Nevirapine symposium sponsored by Boerhinger Ingelheim by Lydia Ruiz, a Spanish investigator, discussing preliminary 24 week data from a lipodystrophy study. The study purpose is to evaluate the clinical, biochemical, immunological and virological impact of switching from a PI to NVP in for patients with lipodystrophy and HIV suppression.

HIV+adults suffering clinically evident lipodystropy were enrolled. They had been on the same protease inhibitor therapy at least 9 months, had baseline CD4 above 100, and HIV-RNA below 400 copies/ml for 6 months. Patients were excluded for prior NVP experience and an OI within prior 4 weeks. Patients were randomized to ddI+d4T+NVP +antihistimines (first 15 days to prevent rash) or to d4T+3TC+same PI. Patients were assessed at screening, baseline, and every 4 weeks thereafter to check whether there was a rebound in HIV-RNA. 3TC was substituted by ddI in order to spare 3TC for rescue therapy in case virologic failure occurred. CD4s, triglycerides (TG), total cholesterol (CHOL), DEXA and anthropometric changes were determined at baseline and every
3 months.

Results
63 of 106 patients recruited (31 in group 1; 32 in group 2) have completed 24 weeks of the study. Evidence of NVP rash was seen in 3 patients in group 1. Plasma viral load was above 400 in 4 patients in group 1 and 3 in group 2.

Treatment Failures and Toxicity

*only 1 discontinued treatment for rash ** not associated with NVP

They observed a significant decline in CHOL from 224 to 203 (p=0.05) at week 24 which continued to week 36. The change in TG was not statistically significant but reduced from 267 at baseline to 210 at week 24; trend appeared to continue on graph at week 36. CD4s increased by small amounts in both groups. About 95% of patients in NVP group had below 20 copies/ml at week 24 and 36. In PI group, about 82% had <20 copies/ml at week 24 and 36. At baseline, about 50% of patients in both group had below 5 copies/ml, while at week 24 70% in NVP group and 60% in PI group had below 5 copies/ml. Anthropometric measurements and DEXA parameters improved in NVP group but differences did not reach statistical significance by week 24. But improvements did occur in measurements at week 24 in abdomen pleat, waist circumfrance, hip circumfrance, and trunk DEXA change. Quality of life improved significantly in the NVP group when patients were surveyed..

Ruiz and Joep Lange, who chaired the session, offered their anecdotal experience. Lange said he has seen improvements in lipodystrophy with patients who switched from PI to NVP. He also said, and Ruiz agreed, it could take a long time to see improvement: one year or more. And Ruiz agreed that some patients show improvements. Some researchers would likely say they want to see longer term hard data before they conclude switching to NVP or efavirenz can reverse lipodystrophy. Ruiz reported normal lactic acidemia and L-carnitine were found in both groups at baseline and week 24. Later in session a report was presented that the use of antihistimines reduced the incidence of NVP rash. I’ll try to report details tomorrow. Its past my bedtime now. Time to watch TV.