Being Alive; November 1997

Merck's Phase II Trial

Merck simultaneously released the results of a phase II trial of efavirenz (DMP-266). In combination with Merck's protease inhibitor indinavir (Crixivan), efavirenz resulted in an average viral load reduction of 2.38 logs (out of a possible 2.49 logs) after 48 weeks of treatment. The average CD4 cell count increase was 240 for the fifty-nine patients who received this combination. A comparison group was given indinavir alone for the first 12 weeks and then the combination; at 48 weeks this group had a 1.89 log average reduction (out of a possible 2.42 logs), and an average CD4 increase of 150.

Eighty-eight percent of the volunteers in the combination arm experienced a viral load reduction to the undetectable range (less than 400 copies), vs. 68% in the comparison group (Crixivan alone for 12 weeks and then the combination).

A Second Trial

Another trial has shown efavirenz to have potent activity in combination with Crixivan (indinavir), at least in relatively treatment-naive patients. Dr. Douglas Mayers of National Naval Medical Center in Bethesda presented results of his trial of efavirenz in combination with Crixivan at the 37th ICAAC. Some 100 asymptomatic HIV+ patients with a history of nucleoside treatment (but not protease inhibitor or non-nucleoside therapy) were randomized into two arms equivalent to those described above: one arm received efavirenz in combination with Crixivan, the other Crixivan alone for 24 weeks. In the first group, viral levels became undetectable in 94% of the patients; in the second group the figure was only 47%.

"Side effects such as insomnia that do occur can be overcome by dividing the dose," Dr Mayers added. "Some patients do develop a rash in the second week of therapy, but you give a non-sedating antihistamine and treat through it, so it's not something that has caused us to withdraw anyone." Efavirenz, a non-nucleoside reverse transcriptase inhibitor, needs to be taken only once a day. It has proven to be effective against many HIV variants which are resistant to other NNRTIs. A warning, however: in laboratory tests, resistance to efavirenz has been shown to develop slowly, so it should never be used alone as monotherapy, only in combination with other antiretrovirals.

Expanded Access

Because of the current limited supply of efavirenz (Sustiva), for the next three months the expanded access program will only be open to those who have had a CD4 count less than or equal to 50, within the last 90 days. Efavirenz "must be used with at least one or more antiviral drugs to which the patient has had no prior exposure," states a company brochure for physicians. "At least one other drug must be changed in a failing regimen if Sustiva is added. Optimally, when possible, the failing regimen should be changed entirely. If a patient is intolerant to an existing antiviral drug and the viral load is undetectable, Sustiva may be substituted for the agent that is not tolerated."

People wishing to enroll in this program must be at least 13, not be "hospitalized for any reason and/or being treated for an acute, serious life-threatening condition such as Pneumocystis carinii pneumonia or sepsis, or requiring IV antibiotics or chemotherapeutic agents." Other exclusions include concomitant use of terfenadine, astemizole, or cisapride, use of NNRTIs within 14 days of beginning this program, certain abnormal lab values, and pregnant or breastfeeding women.

Joint Enrollment In Expanded Access Programs

People in this program may, however, also be receiving experimental medications through other expanded-access programs. DuPont Merck, Glaxo Wellcome, and Gilead are working together to facilitate joint enrollment (for efavirenz, 1592, and adefovir) for appropriate patients, so that patients who are unable to use the approved treatments can start more than one new drug at the same time.

Efavirenz will be provided for free, but people in the program must cover (either through insurance or personally) the expense of CD4 and blood-chemistry lab tests required to qualify for the efavirenz program, and any other expenses.

For more information, call the Sustiva Expanded Access Program, 800.998.6854, 8 a.m. to 6 p.m. Eastern time, Monday through Friday.

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