Mildvan D; International Conference on AIDS.

Int Conf AIDS. 1991 Jun 16-21; 7: 64 (abstract no. TH.B.34).

Beth Israel Medical Center of the Mount Sinai ACTU, New York, NY, USA

OBJECTIVE: To evaluate potential synergy and toxicity of low dose ZDV + IFN-alpha. METHODS: ARC pts with CD4 greater than or equal to 200 and serum p24 greater than or equal to 70 pg/ml were randomly assigned to receive for 12 wks either ZDV at 100, 200, 400, or 600 mg/day (Cohort 1), IFN-alpha at 1, 2, 4, or 6x10(6) U sc/day (Cohort 2), or ZDV + IFN-alpha at 100 mg + 1x10(6) U, 200 mg + 2x10(6) U, 400 mg + 4x10(6) U, or 600 mg + 6x10(6) U/day (Cohort 3), in order to define dose response curves for the Combination Index method of assessing synergy. After 12 wks, Cohort 3 remained on combination Rx, while Cohorts 1 and 2 had IFN-alpha or ZDV, respectively, added to match doses in Cohort 3. Pts were seen 2x/month. RESULTS: 19/27 enrolled pts (target = 48) have now completed greater than or equal to 24 wks of Rx. During wks 1-12, greater than or equal to 50% p24 suppression was seen in 7/8 Cohort 1 pts, 4/7 Cohort 2 pts, and 3/4 Cohort 3 pts. Further p24 declines occurred in Cohort 1 and 2 pts when the second drug was added after wk 12. HIV DNA content by quantitative PCR became transiently (avg. 4 wks) undetectable in 5 Cohort 2 pts (4, during wks 1-8). Toxicities (hepatic, constitutional, hematologic, and myositis) necessitated 50% dose reductions in 9/19 pts (none in Cohort 3; wks 1-12, in 3 Cohort 2 pts; greater than or equal to wk 13, in 4 Cohort 1 and 2 Cohort 2 pts). One Cohort 2 patient voluntarily withdrew at wk 16 and developed lymphoma 3 months later; no other pt has progressed to AIDS. CONCLUSIONS: With partial accrual, we have found: 1) IFN-alpha alone decreased p24 and HIV DNA; 2) ZDV alone and combination ZDV + IFN-alpha was tolerated and suppressed p24; 3) Synergy assessment and optimal dosing/sequencing will require full enrollment.

Publication Types:

• Meeting Abstracts

Keywords:

• AIDS-Related Complex
• Acquired Immunodeficiency Syndrome
• Antigens, CD4
• Antiviral Agents
• Case-Control Studies
• HIV Infections
• HIV Seropositivity
• Humans
• Interferon Alfa-2a
• Interferon-alpha
• Zidovudine
• immunology

Other ID:

• 4003491

UI: 102196778

From Meeting Abstracts