May 2001

Merck working toward HIV vaccine

ATLANTA — Merck scientists recently unveiled data from a 3-month preliminary study geared toward creating an HIV-1 vaccine.

Merck is using Tranzfect technology, a delivery system for DNA-based vaccines first developed by CytRx Corporation, to test different vaccine regimens in rhesus monkeys. For the study, a highly virulent SHIV (a combination of HIV and simian immunodeficiency virus) was used. The vaccines tested were not designed to prevent against SHIV infection, but to slow the progression of SHIV to AIDS. Researchers said the vaccines produced a specific cellular response that reduced the severity of SHIV infection, while slowing the progression to AIDS and death. Researchers were encouraged to find that one vaccine tested (CytRx’s CRL-1005 compound) reduced plasma levels and maintained CD4 cell count after SHIV infection.

Once-daily treatment may simplify dosing regimen

NOORDWIJK, Netherlands — A series of preliminary results from several studies, announced at the International Workshop on HIV Clinical Pharmacology here suggest that a simplified regimen might be effective in controlling HIV.

Researchers looking at the efficacy of once-daily treatment with saquinavir (Fortovase, Roche) plus a mini-dose of ritonavir (Norvir, Abbot) have found that the one-a-day treatment produces results similar to the three-a-day treatment.

In an ongoing study, Fortovase is administered to treatment-naïve HIV-positive patients once daily in 1,600 mg doses along with 100 mg of ritonavir and two nucleoside reverse transcriptase inhibitors. At week four, the Fortovase regimen showed higher levels of concentration in patients and more time covered within 24 hours than previously observed in the currently approved dosage. Levels of tolerability were also high. The most common side effects reported were nausea, diarrhea, vomiting and headache.

In a separate study, 66 patients switched from twice daily Fortovase (1,400 mg) to once daily Fortovase (1,600 mg). At week 24, 100% of patients recorded HIV RNA levels below 400 copies/mL, while 92% maintained a plasma viral load below 50 copies/mL. In the group, the median CD4 cell count increased by 157 cells after 24 weeks.

Sustiva shows long term benefits

ISTANBUL, Turkey — According to recently presented data, the use of efavirenz (Sustiva, DuPont) continues to provide greater viral suppression through three years of follow-up than use of a protease inhibitor. Additionally, when Sustiva is substituted for a protease inhibitor, patients experience greater suppression of viral load.

According to data presented at the European Congress of Clinical Microbiology and Infectious Diseases, 52% of patients from a 1997 study show a reduction of viral load to less than 50 copies/mL compared to 30% in a protease inhibitor-containing regimen. At 144 weeks of follow up, 55% of patients taking Sustiva, AZT and 3TC had viral load less than 400 copies/mL, while 34% of patients taking indinavir (Crixivan, Merck), AZT and 3TC showed similar results.

Sustiva is similarly effective when it used to replace a protease inhibitor-containing regimen. In one study, patients with two years experience in protease inhibitor therapy were randomly switched to Sustiva plus two nucleoside reverse transcriptase inhibitors. The results show that 95% of patients on the Sustiva therapy maintained a viral load of less than 50 copies/mL compared with 74% on the protease therapy. Additionally, Sustiva patients were less likely to discontinue treatment due to adverse effects.