Hydroxychloroquine treatment of patients with human immunodeficiency virus type 1.
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.
Sperber
K
K
Division of Clinical Immunology, Mount Sinai Medical Center, New York, New York, USA.
Louie
M
M
Kraus
T
T
Proner
J
J
Sapira
E
E
Lin
S
S
Stecher
V
V
Mayer
L
L
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006886:Hydroxychloroquine / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000378:metabolism; D018655:Lymphocyte Count / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D015347:RNA Probes; D012367:RNA, Viral / Q000032:analysis; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D015850:Interleukin-6; D015347:RNA Probes; D012367:RNA, Viral; D006886:Hydroxychloroquine