View clinical trials related to HIV Infections.
Filter by:To define relationships between 1) HIV load and risk of CMV disease, 2) CMV load and the risk of developing CMV disease, and 3) CMV load and HIV load. To establish threshold CMV and HIV load values in peripheral blood fractions that are associated with development of CMV end-organ disease. To define the natural history of CMV diseases in the context of highly active antiretroviral therapy (HAART). Establishment of threshold CMV and HIV load values associated with CMV disease would facilitate identification of HIV-infected individuals truly at risk for CMV disease in whom targeted prophylactic interventions to prevent CMV disease would be indicated. These studies would also further the understanding of the natural history of CMV disease within the context of AIDS. Natural history studies conducted prior to the advent of highly active antiretroviral therapy (HAART; i.e., 3-drug regimens that include HIV reverse transcriptase and protease inhibitors) have demonstrated that the risk for developing CMV disease increases with progression of HIV disease and with declining CD4 counts. Presently the need exists to define the natural history of CMV disease in patients with AIDS within the context of HAART.
To evaluate the safety, tolerability and immunogenicity in humans of the APL-400-047 vaccine when administered intramuscularly by needle and syringe at 1 of 3 doses or by Biojector at the intermediate dose. [AS PER AMENDMENT 07/98: To evaluate the tolerability, safety, and immunogenicity of an increased dose in an additional group of volunteers.] DNA-based immunization mimics live-attenuated virus vaccination by stimulation of both the humoral and cellular arms of the immune system; thus, potentially providing the advantages of a live virus vaccination but without the potential risks. It is essential that novel vaccine strategies (including DNA-based immunizations) continue to be developed and enter Phase I human testing because to date, no candidate vaccine from any of the approximately 30 AVEG Phase I or II trials has progressed to a Phase III efficacy trial. Use of a Biojector jet gun for vaccine delivery may also have potential psychological, comfort, safety and immunologic advantages over the traditional needle and syringe method of delivery.
Steps I and II: The purpose of this study is the following: To look at how many patients achieve undetectable HIV blood levels at Week 16. To look at the absolute change in HIV blood levels from the beginning of the study to Week 16. To look at the safety and tolerability of nelfinavir (NFV) and efavirenz (EFV) when used in combination or separately in regimens containing reverse transcriptase inhibitors (RTIs). For the 2 extension studies (Weeks 49 to 144): To look at the proportion of patients whose long-term viral load remains undetectable at Week 96. To look at the time from the beginning of the study to treatment failure, with patients evaluated through Week 144. Step III: To look at the proportion of patients whose HIV blood levels are undetectable 16 weeks after starting the salvage study treatment. To assess safety, toxicity, and tolerance of salvage study drug treatment. (This study has been changed by adding new objectives.) Achieving viral suppression has been widely endorsed as the primary goal of HIV therapy. However, there are few established guidelines for devising combinations of different classes of drugs which will enhance the potential for achieving viral suppression, reducing the risk of toxicity, and preserving therapeutic options for future use. This study includes 2 anti-HIV drugs, NFV (a protease inhibitor [PI]) and EFV (a nonnucleoside reverse transcriptase inhibitor [NNRTI]), for use either alone or in combination with RTI therapy for the purpose of limiting HIV replication. Patients with treatment failure at Week 16 choose 1 of the following 3 alternative salvage therapies: 2-drug PI regimen (saquinavir and ritonavir) plus adefovir dipivoxil and L-carnitine; EFV or NFV (if not already given) plus 2 new approved anti-HIV drugs outside the study; or the best available treatment outside the study. The new RTI, adefovir dipivoxil, is added to the 2-drug PI regimen to achieve suppression of viral replication and thereby delay disease progression. (This rationale reflects a change in the treatment given to patients with treatment failure at Week 16.)
To compare the virologic response between abacavir (ABC, 1592U89) regimens (drug vs. placebo) and between the 2 dosing regimens (BID vs. TID) with respect to the proportion of patients with plasma HIV RNA levels below the limit of detection [AS PER AMENDMENT 8/27/97: < 500 copies/ml at week 16]. To evaluate the safety and tolerance of the study arms. [AS PER AMENDMENT 3/10/99: During the extension period, compare the time to detectable viremia (2 consecutive plasma HIV RNA levels greater than or equal to 500 copies/ml) between ABC and placebo.] Therapeutically, there is a need to explore potent alternative therapy for patients who have received, or are currently receiving, a double nucleoside analog combination including lamivudine (3TC), a regimen that was proven to be clinically inferior to indinavir (IDV) when combined with zidovudine/3TC in study ACTG 320. In order to produce and maintain a maximal antiviral response, all patients in this study will receive 2 or 3 potent, new agents; ABC, a nucleoside analog, EFV, a non-nucleoside reverse transcriptase inhibitor (NNRTI), and IDV, a protease inhibitor. Virologically, the major question this protocol seeks to answer is how prior 3TC exposure in a dual nucleoside regimen influences the response to subsequent treatment. It is unclear whether it is best to add a protease inhibitor either 1) an NNRTI at 1 of 2 doses, or 2) an NNRTI at 1 of 2 doses plus a new nucleoside analog to achieve plasma HIV RNA levels that are below the limits of detection.
To determine the proportion of patients whose plasma HIV-1 RNA level remains below a detectable level (less than 500/ml) after 24 weeks of study therapy with either 141W94 monotherapy or 141W94 plus zidovudine (ZDV) and lamivudine (3TC). To determine the safety and tolerability of 141W94 monotherapy and the combination of 141W94 plus 3TC in patients with HIV infection. Although dramatic inhibition of HIV-1 replication is achieved with ritonavir or indinavir monotherapy, in both cases maximum suppression required combination treatment together with nucleoside analog RT inhibitors. This study tests the hypothesis that monotherapy with 141W94 doses that result in Cmin levels far in excess of the IC90 corrected for plasma protein binding for HIV-1 can achieve the same virologic and immunologic effects in terms of magnitude and durability, as has been observed with combinations of other protease inhibitors plus nucleoside analogs.
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.
For PRAM-1: To evaluate zidovudine (ZDV) + lamivudine (3TC) vs. stavudine (d4T) + ritonavir vs. ZDV + 3TC + ritonavir with respect to the change in plasma HIV-1 RNA copy number from baseline to 48 weeks [AS PER AMENDMENT 1/5/98: 72 weeks; AS PER AMENDMENT 7/17/98: 48 weeks] in stable HIV-infected children with >= 16 weeks of prior continuous antiretroviral therapy. To evaluate the safety and tolerance of ZDV + 3TC vs. d4T + ritonavir vs. ZDV + 3TC + ritonavir based upon laboratory and clinical toxicities. AS PER AMENDMENT 10/20/97: For PRAM-1, Step 2: To evaluate d4T + nevirapine + ritonavir with respect to change in plasma HIV-1 RNA copy number from baseline to 48 weeks in children who have received at least 12 weeks of therapy on the PRAM-1 ZDV/3TC arm and have over 10,000 viral copies at weeks 12, 24, or 36. To evaluate the safety and tolerance of d4T + nevirapine + ritonavir based upon laboratory and clinical toxicities. [AS PER AMENDMENT 10/23/98: To evaluate safety and tolerance of a switch from d4T + ritonavir vs. ZDV + 3TC + ritonavir to d4T + indinavir vs. ZDV + 3TC + indinavir in stable, HIV-infected children with RNA values <= 10,000 copies/ml.] For PRAM-1: Evidence supports combination therapy with 2 or more antiviral agents as beneficial in the long-term management of HIV. The possibility exists that combination therapy may result in a synergistic or additive activity over a prolonged period of time. Also hypothesized is that the development of resistance to individual agents will be developed if viral replication is significantly decreased. AS PER AMENDMENT 10/20/97: For PRAM-1, Step 2: Interim analysis at 12 weeks on PRAM-1 indicates that the proportion of children reaching undetectable RNA levels on the ZDV + 3TC arm is significantly less than the other two arms. The protocol, therefore, has been modified (Step 2) to permit children in the ZDV + 3TC arm with RNA copy number >= 10,000 the opportunity to change to a novel therapeutic regimen (d4T + nevirapine + ritonavir).
To evaluate the safety and efficacy of adefovir dipivoxil in prolonging survival of patients with advanced HIV disease. In CMV prophylaxis substudy: To evaluate the efficacy of adefovir dipivoxil in preventing the development of CMV end-organ disease in patients with advanced HIV coinfected with CMV. The optimal treatment for HIV infection and the prevention of CMV disease has not been identified. Currently available antiretroviral therapies are hampered by both significant toxicities and the development of resistance. In addition, agents for preventing CMV disease, such as oral ganciclovir, are complicated by poor bioavailability and decreased compliance secondary to toxicities. Moreover, discordant results have been reported regarding the effectiveness of oral ganciclovir for preventing CMV disease. There is a need for newer agents with anti-HIV and anti-herpesvirus activity that have good pharmacokinetic and safety profiles and that will be well tolerated by patients. Adefovir dipivoxil is an oral pro-drug of PMEA, a nucleoside analog with activity against a broad spectrum of retroviruses and herpesviruses, including important human pathogens, such as HIV-1, HIV-2 and CMV. Due to its anti-HIV and anti-herpesvirus activity, adefovir dipivoxil may be able to decrease the incidence of opportunistic herpesvirus infections and prolong survival in patients with advanced HIV infection.
To determine the frequency of complete, marked, and partial clinical responses in patients with cryptosporidiosis treated with 6 weeks of NTZ versus 21 days of placebo. To determine the safety of NTZ in subjects with cryptosporidiosis. There is no proven therapy for cryptosporidiosis in persons with AIDS. Nitazoxanide appears to be a good candidate drug for further evaluation because of its effectiveness in preclinical models, the data from early clinical trials and its safety profile. Cooperation between clinical researchers and basic scientists in clinical trials of agents for HIV infection and its complications is a high priority for the ACTG, the NIAID, and the NIH. Thus, it is important to design a clinical trial of NTZ that includes cooperation with basic scientists.
To ascertain whether the origin of plasma HIV-1-RNA following T cell activation represents the activation of latently infected cells or an increase in cells permissive for replacing viral mutants. The mechanism by which immune stimulation increases circulating levels of HIV-1 is not known. In particular, it is uncertain whether the transient increase in plasma HIV-1 RNA is due to enhanced replication of an actively replicating pool of HIV-1, or is due instead to activation of proviral sequences in previously resting CD4+ cells. One approach to discriminate these alternatives is a "molecular pulse-chase" experiment. In this approach, drug resistant mutants would be selected by administration of Lamivudine (3TC).