Active clinical trials for "HIV Infections"

To determine the safety and tolerability of hydroxyurea at two doses alone and in combination with didanosine (ddI). To compare the short term antiviral effect of ddI monotherapy versus hydroxyurea plus ddI, as measured by plasma RNA levels at 8 weeks of therapy. [AS PER AMENDMENT 10/1/97: Accrual to arms involving hydroxyurea alone has been closed.] Current antiviral therapies for HIV-1 are limited by a few choices, and the lack of sustained clinical benefit from the drugs. The mechanisms that account for the lack of prolonged inhibition of viral replication by these agents are not fully understood. The activity of RT inhibitors might be potentiated by inhibiting host cellular enzymes essential for efficient HIV reverse transcription. Based on this information, comparisons of the antiviral effects of ddI monotherapy and hydroxyurea plus ddI, with the cellular enzyme ribonucleotide reductase as a potential target, should be done.

To compare the proportion of patients who sustain suppression of plasma HIV RNA to undetectable levels [AS PER AMENDMENT 09/19/97: below 200 copies/mL by Roche UltraSensitive assay] among the 3 regimens during the maintenance phase. The objective of antiretroviral therapy is to reduce HIV replication, preserve immunologic function and delay the development of HIV-related complications. In patients administered potent antiretroviral regimens, HIV RNA levels are reduced below 500 copies/ml of plasma and below the level of detection of commercially available assays. This protocol attempts to learn if a less intensive regimen can successfully sustain viral suppression after induction with a triple-drug regimen. The study also addresses whether HIV can be eradicated in patients following prolonged treatment with induction and maintenance regimens.

1) To determine whether it is possible to remove and culture (increase in number and activate) in the laboratory, CD8(+) lymphocytes (white blood cells) from HIV-infected patients receiving zidovudine (AZT); 2) To determine the toxicity of returning to the patients intravenously the expanded and activated autologous cells (given to the patient from whom they were taken), with and without giving the patients recombinant interleukin-2 ( aldesleukin; IL-2 ) at the same time; 3) To radiolabel (mark) the CD8(+) lymphocytes with Indium 111, and then scan the patients to determine the distribution of the CD8(+) lymphocytes in those who are and are not given IL-2 infusions; 4) To determine the toxicity of IL-2 given at the same time with autologous CD8(+) lymphocytes; 5) To measure changes in the immunology of the subjects following these treatments. CD8(+) cells are suppressor/killer lymphocyte cells that act to limit replication of viruses. It is hoped that the reinfusion of activated autologous CD8(+) cells into patients with AIDS will help to control opportunistic infections such as cytomegalovirus and toxoplasmosis (two of the leading causes of sickness and death in AIDS patients). This treatment may also stop the HIV virus from replicating (reproducing itself) in the AIDS patient. Further activation of these cells, once infused, may be necessary. It is hoped that IL-2 will stimulate the patient's immune system against the AIDS virus along with the activated CD8(+) cells. Thus, IL-2 will be given, and its effects studied.

To evaluate how the drug dextran sulfate (DS) is absorbed by the stomach and intestines when taken by mouth. To evaluate its effect on blood coagulation. DS has been reported to have anti-HIV activity. However, it is not known how much of the drug is absorbed into the bloodstream and can be used by the body when DS is taken by mouth.

To determine the safety and effectiveness of treatment with ribavirin (RBV) plus isoprinosine (INPX) in preventing the development of AIDS in patients infected with the AIDS virus (HIV). Also to determine the maximal dose of RBV that can be tolerated by HIV-infected patients when RBV is given with INPX. The patients may or may not have generalized lymphadenopathy syndrome (LAS). RBV has prevented the development of AIDS in some HIV-infected patients with LAS and INPX has stimulated the immune system of patients infected with HIV. The immune system fights infections in the human body, and the HIV attacks T cells that are an important part of the immune system. Reports from individual cases treated with both RBV and INPX suggest that clinical improvements occurred in HIV-infected patients, but there is no reliable information on the safety and effectiveness of this drug combination in such patients.

To test whether zidovudine (AZT) is useful as a treatment for the neurologic syndrome called AIDS dementia complex. To determine how long AZT takes to reach cerebral spinal fluid (CSF), how long, and at what concentration it is found there. HIV infection can result in impairment in the function of the brain and spinal cord, leading to disturbances in the ability to think clearly and in strength and coordination. This disorder, which has been called the AIDS dementia complex, may be due to a direct effect of HIV on the nervous system. It is known that AZT does get into the brain to some extent, where it may reduce growth of HIV. It is hoped that AZT will stabilize or improve the symptoms of the AIDS dementia complex.

To evaluate the long-term safety and effectiveness of the drug 2',3'-dideoxycytidine ( zalcitabine; ddC ) in treating patients with AIDS or advanced AIDS related complex ( ARC ). Recent studies show that a certain group of drugs (dideoxynucleosides) are effective in treating patients with HIV infection. ddC is a dideoxynucleoside and test tube studies show that it may be valuable in treating AIDS patients. ddC has been shown to be well tolerated in certain patients with AIDS.

Part I studies the effect of quinine on how zidovudine (AZT) is used by the body and eliminated through the kidneys in HIV infected patients. Part II studies the effect of probenecid and quinine on the same aspects. Because AZT leaves the bloodstream quickly, patients must take the drug frequently to keep adequate amounts in their bodies. Probenecid and quinine may slow down the rate at which AZT leaves the body. Therefore, taking these drugs along with AZT may reduce the amount of AZT needed for treatment.

To determine the safety of ampligen at several doses in HIV-infected patients who have not yet developed AIDS or advanced AIDS related complex (ARC). Biologic, antiviral, and immunologic effects will be studied. Evidence indicates that a long period with no symptoms follows infection with HIV. Individuals who are infected with the virus could benefit from therapy with a drug that acts to kill the virus or to stimulate the immune system of the individual or both. The immune system is the means the human body has for fighting infections. Ampligen is a suitable drug for clinical trials against HIV because it has been shown to stimulate the immune system and to inhibit HIV in vitro (test tube) at drug levels that can be achieved without noticeable clinical side effects.

To determine the safety and tolerance of alvircept sudotox (sCD4-PE40) given at various dosing intervals and concentrations. To determine whether frequent dosing alters immunogenicity or toxicity. To obtain preliminary data to ascertain whether sCD4-PE40 has activity against HIV in human subjects. To determine whether there is any additive toxicity with combined use of sCD4-PE40 and zidovudine (AZT). There is some evidence that AZT and sCD4-PE40, an experimental drug with anti-HIV activity previously demonstrated in vitro, may produce increased benefit when used in combination in HIV-infected patients.