HIV AIDS News [International Conference on AIDS (12th: 1998: Geneva, Switzerland)]

Durable clinical anti-HIV-1 activity (72 weeks) and tolerability for efavirenz
(DMP 266) in combination with indinavir (IDV) [DMP 266-003, Cohort IV]
12th World AIDS Conference
June 28 - July 3, 1998
Geneva, Switzerland
S. Riddler, J. Kahn, C. Hicks, D. Havlir, D. Stein, J. Horton, and N. Ruiz
University of Pittsburgh, Pittsbugh, PA; San Francisco General Hospital, San
Francisco, CA; Duke University, Durham, NC; UCSD Treatment Center, San
Diego, CA; Albany Medical College, Albany, NY; and Carolinas Medical
Center, Charlotte, NC and The DuPont Merck Pharmaceutical Company,
Wilmington, DE.
Introduction: Efavirenz (EFV, SUSTIVATM, DMP 266) is an investigational
nonnucleoside reverse transcriptase inhibitor (NNRTI). Pharmacokinetic
evaluation supports once-daily administration.
Objectives: Evaluate the safety, tolerability, and long-term antiretroviral
activity of EFV (200 mg qd increased to 600 mg qd at 36 weeks) and IDV
(800/1000 mg q8h) given in combination compared with that of IDV
(800/1000 mg q8h) alone in asymptomatic or mildly symptomatic patients.
Dosing: Fifty-nine patients randomized to EFV+IDV initiated treatment with
both drugs simultaneously. Forty-two patients randomized to initiate
treatment with IDV alone subsequently added d4T and EFV after 12 weeks.
Methodology: Multicenter, blinded study (101 patients) with plasma samples
taken at defined intervals. HIV-1 RNA (copies/mL) determined by RT-PCR
(Amplicor~); CD4 (cells/mm3) determined by flow cytometry. Demographics:
Men=86%; age=38.5 years (+8.0); prior NRTI therapy=71%; mean years
HIV+=5.0~3.6. Baseline Values: Mean plasma HIV RNA=5.06 logio ~0.55;
mean CD4=283~118 cells/mm3. Preliminary Results: At 60 weeks, the
percentage of patients with plasma HIV RNA below quantifiable levels (BQL),
(BQL= <400 copies/mL) was: EFV+IDV=89%; IDV+d4T+EFV=68%. Mean
loglo decrease in plasma HIV RNA (truncated at 400 copies/mL) at 60 weeks:
EFV+IDV=-2.5+0.09; IDV+d4T+EFV=-1.9+0.20. Mean increases at 60 weeks
for CD4 count: EFV+IDV=+267 (+26) cells/mm3; IDV+d4T+EFV=+210(+36)
cells/mm3. Seventy-two (72) week updates of this data will be presented.
Tolerability. Both treatment arms were generally well tolerated out greater
than 1 year at 72 weeks. Updated tolerability data will be presented.
Conclusion: EFV dosed once daily in combination with IDV provides
sustained, durable, viral suppression.