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  9th Conference on Retroviruses and Opportunistic Infections
Seattle, Washington, February, 2002
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New Drugs Reported at 9th Retrovirus Conference
Reported by Jules Levin
  Two new, second generation NNRTIs showed effectiveness in studies for patients with resistance to nevirapine or efavirenz. TMC-125, from Tibotec-Virco, showed a 0.9 log reduction in a 7-day study of 16 patients with extensive NNRTI resistance. Patients stayed on the same nukes for the 7-day study. In a second 7-day study of TMC-125 monotherapy in 12 treatment-naive patients, the viral load decline was a potent 2 log and the initial viral load decline was as rapid as seen with a 5-drug triple-class regimen. Both study authors commented on the potency of this drug, in early studies.
Another second generation NNRTI called DPC-083 from Bristol Myers also showed potency for patients with resistance to efavirenz or nevirapine, and for patients naive to treatment. 4/10 patients (on-treatment analysis) who did not add new NRTIs but simply switched their NNRTI to DPC-083 had <400 copies/ml after 8 weeks; 72% of patients who added 1 new NRTI had <400 copies/ml. The viral load reduction was more than 1 log. In a second study of DPC-083 in treatment-naive patients, this drug appeared to be as potent as efavirenz. Although patients experienced rash and CNS side effects, the rate appeared to be less than that seen with efavirenz in the lower DPC-083 dose groups. When using the higher DPC-083 dose rash frequency was higher than for efavirenz. So the dose for treatment-naive patients has been identified , but not yet for NNRTI resistant patients. More study is needed.
10 treatment-naive patients received Tenofovir once daily monotherapy. They were hospitalized for the first 72 hours to monitor their viral load reductions closely. Their viral load was 20,000 and CD4s were 600+. 6 were African-American and 9 men. The median viral load reduction was 1.6 log at day 21. And the initial decline in viral load was as rapid as with Norvir monotherapy. The study authors concluded Tenofovir is as potent as a potent PI. And that further studies are warranted in treatment-naive patients. The implications from this study are that Tenofovir may be useful as a first-line therapy. Doctors recommend following kidney related lab tests every 2 months while on therapy. Tenofovir appears to be easy to tolerate and the once per day dosing is convenient.
Initial information was presented on the first integrase inhibitor (S-1360) from Shionogi-Glaxo Smith Kline to reach this far in development. It showed potent antiviral activity against viruses from patients in the test tube. It was synergistic in the test tube with other HIV ART medications. The preclinical safety data is so far good. And the drug appears to be active against the integrase target.
There were two interesting presentations on entry inhibitors in development. Bristol Myers announced for the first time at a conference their development program for entry inhibitors. They presented on an entry inhibitor it appears they will try to develop.
Schering Plough presented data in HIV+ humans on their entry inhibitor. SCH-C has a 24 hour half-life, which suggests it can be dosed once daily. Schering reported data from a study in 12 HIV+ patients who received 25 mg twice a day of SCH-C monotherapy. CD4 counts were >250; viral load was 5000-200,000, and it was a 10-day study. Higher dosing, 50 and 100 mg bid was given in this study but results weren't presented. CD4s were 377 and viral load was 38,000 on average. There were no discontinuations due to adverse events. 7/12 reported at least 1 AE: headache, bad taste. There was 1 severe AE. The concern about this drug is that it prolongs QT. This relates to heart beats. It is not known if this is a significant & prohibitive problem yet. 10/12 patients had at least a 0.50 log reduction. The viral load rebound after stopping drug was slow. And the viral load decline was steep after a couple of days. Some patients had 1.0 or 1.4 log reductions. The presenter said the drug was well tolerated, and the QT effect was small. Schering also has SCH-D as a backup to this drug.
These studies presented very encouraging information saying the drug pipeline for patients with drug resistance is promising. as well, the new drugs--2 new entry inhibitors, and an integrase inhibitor offer new treatment options and strategies. More detailed reports on these drugs and the conference will follow.