A Study on the Effect of Chemotherapy Combined With Anti-HIV Drugs in HIV-Positive Patients
Condition: HIV Infections
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to determine the safety of anti-HIV drugs combined with low-dose
      chemotherapy (consisting of cyclophosphamide [CTX]) in HIV-positive patients. This study
      examines whether this combination therapy can reduce the number of HIV-infected cells hidden
      in the lymph nodes and blood.

      Current anti-HIV drug treatments can greatly reduce the levels of HIV in the human body.
      However, HIV can hide in certain immune cells and escape the drugs' effects. Chemotherapy
      using CTX destroys these immune cells. When used with standard anti-HIV drug treatments, CTX
      may be able to speed up the elimination of HIV-infected cells.
    

Detailed description: 
      HAART is a potent suppressor of plasma and lymph node HIV RNA. However, studies suggest that
      HAART cannot significantly diminish reservoirs of chronically HIV-infected cells. Strategies
      designed to eradicate all HIV infection should seek to actively target these reservoirs. CTX
      administration has been shown to eliminate a large number of lymphoid tissue T cells and
      macrophages, appearing to actively target chronically HIV-infected cells. As lymphoid organs
      are repopulated following initial depletion with CTX, HAART may protect repopulating cells
      from becoming HIV-infected, resulting in a net additional removal of the HIV-infected
      lymphoid reservoir.

      In Step 1 of this 2-step protocol, all patients receive a HAART regimen of nelfinavir (NFV)
      plus stavudine (d4T) plus lamivudine (3TC). Patients who achieve an acceptable virologic
      response, defined as 2 consecutive HIV RNA determinations below 500 copies/ml at least 2
      weeks apart between Weeks 4 and 16 of Step 1 [AS PER AMENDMENT 10/30/98: defined as 2
      consecutive plasma HIV RNA determinations below 50 copies/ml by the Roche Ultrasensitive
      assay within a 4-week period between Weeks 4 and 24], are randomized to Arm A or B of Step 2.
      In Arm A, patients receive NFV plus d4T plus 3TC. In Arm B, patients receive NFV plus d4T
      plus 3TC plus 3 escalating doses of CTX at 6-week intervals. Patients in both arms are
      followed for at least 52 weeks following randomization to Step 2. During this time, patients
      undergo blood tests and lymph node biopsies to measure HIV DNA and RNA levels and to
      characterize the T cell population. Additionally, patients undergo a chest CT of the thymus
      before randomization to Step 2 and at Week 52 of Step 2. Cerebrospinal fluid may be obtained
      at Week 52 to determine the amount of HIV RNA and DNA present. [AS PER AMENDMENT 10/30/98:
      G-CSF is given after the first dose of CTX, at the discretion of the investigator, and after
      the second and third doses, for up to 14 days, until the absolute neutrophil count is 10,000
      cells/mm3. Also, CTX doses may be modified based on pharmacokinetic study results.]
    

Intervention name(s): Nelfinavir mesylate; Lamivudine; Filgrastim; Stavudine; Cyclophosphamide
Intervention type(s): Drug; Drug; Drug; Drug; Drug
Intervention MeSH terms: Lamivudine; Stavudine; Nelfinavir; Cyclophosphamide
Primary purpose: Treatment
Keywords: Cyclophosphamide; Dose-Response Relationship, Drug; Drug Therapy, Combination; Granulocyte Colony-Stimulating Factor; Combined Modality Therapy; Antineoplastic Agents; Lymph Nodes; Stavudine; HIV Protease Inhibitors; Lamivudine; DNA, Viral; RNA, Viral; Reverse Transcriptase Inhibitors; Anti-HIV Agents; Nelfinavir; Antineoplastic Agents, Alkylating