       Document 0226
 DOCN  M9650226
 TI    Hydroxychloroquine treatment of patients with human immunodeficiency
       virus type 1.
 DT    9605
 AU    Sperber K; Louie M; Kraus T; Proner J; Sapira E; Lin S; Stecher V; Mayer
       L; Division of Clinical Immunology, Mount Sinai Medical Center, New;
       York, New York, USA.
 SO    Clin Ther. 1995 Jul-Aug;17(4):622-36. Unique Identifier : AIDSLINE
       MED/96098329
 AB    Hydroxychloroquine (HCQ), an antimalarial agent used to treat patients
       with autoimmune diseases, has been shown to suppress human
       immunodeficiency virus type 1 (HIV-1) replication in vitro in T cells
       and monocytes by inhibiting posttranscriptional modification of the
       virus. These in vitro observations have been expanded into an in vivo
       study of HCQ as a potential anti-HIV-1 agent in HIV-1-infected patients.
       A randomized, double-blind, placebo-controlled clinical trial was
       conducted in 40 asymptomatic HIV-1-infected patients who had CD4+ counts
       between 200 and 500 cells/mm3. Patients were randomly assigned to
       receive either HCQ 800 mg/d or placebo for 8 weeks. Virologic and
       immunologic parameters, including HIV-1 ribonucleic acid (RNA) via use
       of polymerase chain reaction, viral culture, antigen and mitogen
       responses, and proinflammatory cytokine levels were measured at the
       beginning and end of the study. The amount of recoverable HIV-1 RNA in
       plasma declined significantly in the HCQ group over the 8-week period (P
       = 0.022), while it increased in the placebo group. The percentage of
       CD4+ T cells remained stable in the HCQ-treated group (18.1 +/- 9.2%
       before treatment vs 18.6 +/- 10.5% after treatment) and fell
       significantly in the placebo group (21 +/- 7% before treatment vs 19.3
       +/- 6.3% after treatment; P = 0.032). However, this was not reflected as
       a change in absolute CD4+ counts for either group (HCQ, 262.8 +/- 166
       cells/mm3 vs 251 +/- 163 cells/mm3; placebo, 312 +/- 121 cells/mm3 vs
       321 +/- 124 cells/mm3). Mitogen- and antigen-specific responses remained
       constant in the HCQ group while T cell proliferative responses to
       Candida decreased in the placebo group (4.8 +/- 3.6 x 10(3) SI
       [stimulation index] vs 3.0 +/- 3.0 x 10(3) SI; P = 0.032). Lastly, serum
       interleukin 6 levels declined in the HCQ group (14.3 +/- 13.5 U/mL vs
       12.0 +/- 16.7 U/mL; P = 0.023) but not in the placebo group (11.3 +/-
       8.8 U/mL vs 7.0 +/- 11.7 U/mL); this was coincident with a decrease in
       serum immunoglobulin (Ig)G (2563 +/- 1352 mg/mL vs 2307 +/- 1372 mg/dL;
       P = 0.032), compared with the placebo group (2733 +/- 1473 mg/dL vs 2709
       +/- 1501 mg/dL). No other parameters, including serum p24 and beta-2
       microglobulin levels, were altered by HCQ therapy. HCQ thus may be
       useful in the treatment of patients with HIV-1 infection.
 DE    Acquired Immunodeficiency Syndrome/*DRUG THERAPY/IMMUNOLOGY/  VIROLOGY
       Adult  Antiviral Agents/ADVERSE EFFECTS/PHARMACOKINETICS/*THERAPEUTIC
       USE  Base Sequence  CD4-Positive T-Lymphocytes/DRUG EFFECTS
       Double-Blind Method  Female  Human  Hydroxychloroquine/ADVERSE
       EFFECTS/PHARMACOKINETICS/*THERAPEUTIC  USE  *HIV-1/DRUG
       EFFECTS/PHYSIOLOGY  Interleukin-6/METABOLISM  Lymphocyte Count/DRUG
       EFFECTS  Male  Middle Age  Molecular Sequence Data  RNA Probes  RNA,
       Viral/ANALYSIS  Support, U.S. Gov't, P.H.S.  Virus Replication/DRUG
       EFFECTS  CLINICAL TRIAL  JOURNAL ARTICLE  RANDOMIZED CONTROLLED TRIAL

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

