The Bay Area Reporter - January 12, 1998
Don Howard and Matt Sharp, ACT UP/Golden Gate

In mid-December, after sometimes heated negotiations between the company and AIDS activists, the drug was made available in a very limited program only to people whose immune systems were dangerously compromised. In a meeting last week with AIDS activists, the company agreed to amend the program to allow anyone who has failed currently available drugs to access Preveon as a final option to construct a cocktail that might bring their virus under control.

ACT UP/Golden Gate played a central role in the design of Preveon's expanded access program and has supported other access programs for people who have failed older HIV therapies and need new options (including Glaxo's Abacavir/1592 program). It has taken a while for Gilead to understand the importance of making Preveon available to all patients who have failed drugs. We are hopeful that this expansion will increase options for people with AIDS and save lives. A recent study by Dr. Steven Deeks at UCSF showed that over 50% of patients at San Francisco General Hospital's Ward 86 had failed drug treatment - largely due to years of previous treatment.

Preveon is being released at the same time as two other new anti-HIV drugs, Sustiva/DMP266 from DuPont Merck (a non-nucleoside reverse transcriptase inhibitor), and Abacavir/1592 (another nucleoside) from Glaxo Wellcome. Activists felt it was important for the inclusion criteria of the three programs to allow patients to access all three drugs simultaneously as a new untried cocktail of drugs. They fought successfully to have the programs open to all people who are not able to construct a viable treatment regimen based on the Department of Health and Human Services' current treatment guidelines. DuPont Merck and Glaxo Wellcome had agreed to expand their programs; Gilead was the last to adopt the more inclusive criteria.

Preveon has been studied in a smaller number of people than other drugs in this stage of development, and the drug has a number of potential side effects. It is important for patients and their doctors to weigh the pros and cons of using Preveon in light of the scant data. In December, the company reported to activists that, of the 800 patients who have taken Preveon in studies, approximately 100 (13%) experienced moderate to severe toxicities (grade 3 or 4). One of the more worrisome potential toxicities reported to date is elevated serum creatinine levels (4%), an indication of kidney dysfunction. Elevations in certain liver and pancreas enzymes have also been observed. Other side effects reported include nausea and anorexia.

Preveon can also cause a decrease in serum-free carnitine. Severe depletion of carnitine may cause weakness, fatigue, low blood sugar, confusion, and abnormalities in liver function. The company is including a daily carnitine supplement at no charge with Preveon as part of the expanded access program.

Side effects were reversed when the drug was stopped or the dose reduced. Doctors are advised to monitor the patient routinely while using Preveon, because toxicities often develop six months or more after starting treatment. Preveon should be used with at least one or two other drugs that the patient has not previously taken.

Tide, not side

Preveon is the first of a new type of anti-HIV drugs called nucleotide analogues which are active in a broader range of cells than other drugs. Unlike older nucleoside analogues such as AZT, ddI, ddC, d4T, and 3TC, nucleotide analogues like Preveon do not require the presence of certain cellular enzymes (particularly nucleoside kinase) to become active. Preveon can be active in cells without this enzyme - specifically, monocytes/macrophages. Preveon also has antiviral activity against Hepatitis B and a wide range of herpesviruses.

Preveon has a long half-life and can be administered once daily. The current dose being used is 120 milligrams (mg.), but the company is testing the efficacy of Preveon at 60 mg. in an ongoing trial. If the efficacy at the two doses appears equivalent, patients enrolling in the expanded access program will be given the choice of receiving the 120 mg. dose or being assigned to a sub-study which would randomize them to either the 60 mg. or 120 mg. dose. There is hope that the 60 mg. dose would be as effective but have fewer side-effects than the higher dosage.

To be eligible for the Preveon expanded access program, the patient must be at least 13 years of age and have failed or be intolerant to at least two available nucleoside analogs (like AZT) and one protease inhibitor. Based on the agreement reached with activists this week, the only other requirement for access is a physician's statement that the patient is unable to construct a viable treatment regimen without Preveon.

Information for enrollment will be sent to the patient's primary care physician by calling (800) 445-3235. (Press "1" when prompted.) t

Clarification

The ACT UP/Golden Gate Writers Pool column titled "News from the HIV Research Front," published on November 27, incorrectly reported on a discovery by Bruce Walker's team at Massachusetts General Hospital and Harvard (later published in Science). Our earlier report discussed the importance of maintaining a CTL response to the virus for long-term survival. While this was correct, Dr. Walker's most recent work showed that, unlike most people with HIV infection, long-term non-progressors also maintain a vigorous HIV-specific CD-4+ T-cell response to the virus.

According to Walker's recent research, people treated with drug therapy shortly after infection (but before becoming HIV antibody-positive) generated virus-specific CD-4 responses as their viral load was reduced to undetectable levels. This contrasts with the reported lack of strong HIV-specific CD-4 responses after starting drug therapy during chronic infection.

Walker suggests that during acute infection, HIV-specific CD-4s that are activated to fight the infection are particularly susceptible to being depleted. Drug treatment during this very early stage of infection may therefore help preserve HIV-specific CD-4s, which could provide longer AIDS-free survival for those with HIV.
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