Some Key New Data on Drugs - Report #5
from Jules Levin
Geneva, July 2, Thursday, 2pm
Cant wait to come home to the good old USA and NYC-big apple. Who said Europe is so great. Here in Geneva, the food stinks, the hotels mostly stink, there is suboptimal air conditioning throughout the city, the service stinks, and it is a dirty city. I prefer NYC dirt to Geneva dirt.
New data is being presented here on the following:
efavirenz (Sustiva, DMP-266)
In a naive population abacavir plus AZT/3TC was compared to AZT/3TC. I think the researchers showed 6 months of CD4 and viral load changes. The viral load reduction from this 3 NRTI regimen was comparable to a PI or NNRTI 3 drug regimen. Of course, for those who are NRTI experienced the antiviral effect may be different. In the May NATAP Reports and more extensively on our web site are a series of articles about abacavir resistance, cross-resistance and antiviral activity for individuals with NRTI experience. At the Retrovirus Conference data was reported on the correlation of abacavir viral load reductions and prior NRTI experience. Phenotypic resistance to abacavir correlated with anitiviral activity. Individuals with <4 fold abacavir phenotypic resistance were sensitive to abacavir; those with 4 to 7 fold resistance had less but some sensitivity to abacavir and those with 8 fold resistance did not respond to abacavir. They used the Virco phenotypic resistance test for this study. The test will be commercially available in the USA through LabCorp in July 98, although currently it is expensive. The level of phenotypic resistance to abacavir was reported to be associated with the previous NRTI experience one has, the number of NRTIs one has resistance to and the amount of resistance to the NRTIs. The more NRTIs one had resistance to and the higher level of resistance you had to the NRTIs the more likely you were to have phenotypic resistance to abacavir. But experience with AZT, 3TC or AZT/3TC did not in and of itself cause full resistance (8 fold) to abacavir.
PNU-140690 is the new Upjohn protease inhibitor. This PI was added to a double NRTI regimen a small number of individuals were taking. Three doses were administered to 8 persons each: 900, 1200 and 1500 mg tid. The peak viral load drop at day 11 was about 1.0, 1.3, and 1.3, respectively. By week 12 the viral load rebounded to 0.5 to 0.7 log reductions from baseline. Adding 140690 to current NRTI therapy probably will not show the drugs optimal antiviral activity. Data will be presented on this drugs activity in an initial study of individuals with PI failure.
In an initial study of ABT-378 in treatment naive individuals preliminary data showed 91% were undetectable (<400 copies/ml) and the drug was tolerable after 24 weeks (n=11). There were no reported discontinuations. The dosing was either 200 mg 378 plus 100 mg RTV bid or 400 mg 378 plus 100 mg RTV bid. After 3 weeks of 378/RTV alone d4T/3TC was added. The median HIV RNA reduction was 2.2 log, and the median CD4 increase was 150 cells. There was no difference in the activity between the two doses. Abbott is expected to explore 378s use in persons resistance to PI(s) in the Fall.
Efavirenz+AZT/3TC (protease sparing regimen) has been compared in clinical studies to EFV+IDV and IDV+AZT/3TC. Preliminary data after 6 months showed the EFV+AZT/3TC regimen to have at least comparable improvements in CD4s and viral load as the other two regimens. Efavirenz is taken once a day.
Initial preliminary data was reported for a once a day regimen consisting of nevirapine, ddI and 3TC. It is the first data Ive seen on once a day dosing of 3TC or nevirapine. The regimen was given to individuals taking methadone. After about 6 months 9/10 had <50 copies/ml. After about 10 months 85% had undetectable viral load using a standard assay.
The May 98 NATAP Reports has a detailed report on FddA which may not be cross-resistant with other NRTIs. It is from the ddI family so it may be synergistic with hydroxyurea. FddA so far does not appear to have the side effects or toxicities as ddI.
At the Late Breaker session on Friday more data will be presented. Additional data will be reported upon return to NYC on web site, in newsletter, and at foum NATAP is holding at NYU Medical Center on Saturday, July 18, in Farkas Auditorium at 1st Ave and East 31st St from 10am to 3pm. Call NATAP office for reserved seating at 212 219-0106. We will review important information from Geneva and the Intl Workshop on Resistance and Treatment Strategies.