Active clinical trials for "HIV Infections"

To determine if intravenous (IV) and oral zidovudine (AZT) can be safely given to children aged 1 day to 3 months who were born to mothers with an HIV infection. Also to determine the correct dose of AZT for young children. Of a total of 908 pediatric AIDS cases, 78 percent have acquired HIV infection from a mother with HIV infection or at high risk for acquisition of HIV, and the number of cases in children is expected to increase over the next several years. AZT therapy may be effective in altering the course of the disease and decreasing the high mortality in these children. It is also possible that early intervention with AZT may prevent the establishment of HIV contracted before, during, or just after birth.

To compare the efficacy, safety and tolerance, and other clinical and immunologic effects of zidovudine (AZT) plus zalcitabine (dideoxycytidine; ddC), AZT plus didanosine (ddI), and AZT alternating monthly with ddI as measured by differences in survival among HIV-infected persons who have received 6 or more months of nucleoside monotherapy and have a CD4 count greater than or equal to 50 cells/mm3. Combining two nucleoside drugs has the theoretical advantage of optimal protection against the evolution of resistant strains of HIV. However, one major problem with combination nucleoside therapy in patients with advanced disease is the increased toxicity resulting from such therapy. One approach to minimize toxicity while perhaps retaining some of the benefits of combination therapy is to alternate the two drugs.

PRIMARY: To determine the efficacy and toxicity of three treatment regimens: saquinavir mesylate (Ro 31-8959) plus zidovudine (AZT) vs. AZT plus zalcitabine (dideoxycytidine; ddC) vs. Ro 31-8959 plus AZT plus ddC. SECONDARY: To investigate the pharmacokinetics and effects on various clinical parameters of the three regimens.

To determine the effects of zidovudine (AZT) alone and in combination with didanosine (ddI) on viral load in the lymphoid tissue and blood of antiretroviral-naive, HIV-infected patients with CD4 counts greater than or equal to 550 cells/mm3. Recent studies have shown that during the asymptomatic phase (clinical latency) of HIV infection, there is an extraordinarily large number of infected CD4+ lymphocytes and macrophages throughout the lymphoid system, both in latent and productive states. These findings support the belief that early intervention therapy with reverse transcriptase inhibitors could prolong the clinical latency period.

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.

This is a randomized, double blind study of the safety and immunogenicity of APL 400-003, a plasmid DNA vaccine encoding the env and rev genes of HIV-1, in HIV-negative volunteers. Three doses of vaccine are being tested: 100, 300, and 1000 micro g. 8 volunteers per dose will be randomized: 6 to plasmid vaccine, and 2 to a vehicle control. Immunizations will be administered at day 0 and weeks 4 and 8, with a booster immunization administered at week 24. An additional 5 volunteers may be included in an open manner at the dose likely to be used in subsequent studies. The primary aims of the study are to determine: 1. the safety of APL 400-003, as evaluated by clinical and laboratory safety parameters and 2. the immunogenicity of APL 400-003, as determined by a broad range of laboratory assays. Up to 33 patients (allowing for drop-outs) will be enrolled in the study, and volunteers will be followed for one year after immunization.

To make lamivudine (3TC) available to patients with progressive, symptomatic HIV disease who cannot participate in a controlled clinical trial and who are refractory or unable to tolerate other therapies. To collect data pertaining to the safety of 3TC at two dose levels. To evaluate the effect of 3TC on markers of hepatitis B in co-infected patients at five to ten selected sites.

To examine the safety and tolerance of three doses of oral vesnarinone in HIV-infected patients with CD4 count > 300 cells/mm3.

To evaluate the anti-HIV activity, safety, and tolerance of adefovir dipivoxil ( bis-POM PMEA ) in combination with standard antiretroviral therapy for 48 weeks.