View clinical trials related to HIV Infections.
Filter by:The objective of this study is to evaluate the safety and utility of bacteriophage phi X174 immunization as a tool to assess the immune competence of HIV-infected patients at different stages of disease in vivo, and to assess the impact of viral load levels and therapy-induced changes in viral load levels on the response to immunization with the neo-antigen bacteriophage phi X174. Bacteriophage phi X174 immunization is a method that has been in use for more than 25 years to assess the immunity of patients with various types of primary and secondary immunodeficiencies, including 48 HIV-infected patients. This is a prospective open-label, controlled study which will enroll 39 HIV-infected patients and 13 healthy volunteers, male or female with 18 years of age and over. The HIV-infected patients will be divided into 3 groups according to their CD4 cell count: less than 200 cells/mm(3), between 200 and 500 cells/mm(3) and greater than 500 cells/mm(3). After screening and a two week pre-study evaluation, all eligible participants will receive a primary, secondary and tertiary immunization with 2 x 10(9) PFU/kg of bacteriophage phi X174 six weeks apart. Patients who present with detectable levels of viral load at entry will be offered a more effective antiviral drug regimen. Patients will have to be on a stable antiviral regimen for at least one month prior to receiving the primary immunization. Patients will return for visits 1, 2 and 4 weeks after each immunization for clinical and laboratory evaluations. The study endpoints are: safety (as measured by incidence of adverse events, CD4 cell count and HIV plasma RNA), kinetics of bacteriophage clearance following primary immunization, quantitation of bacteriophage phi X174 specific antibody titers following primary, secondary and tertiary immunizations and determination of qualitative and quantitative antibody isotype switching following secondary and tertiary immunizations.
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.
This study will test the safety and effectiveness of genetically altered T lymphocytes (white blood cells of the immune system) in reducing viral load in patients infected with the human immunodeficiency virus (HIV). The lymphocytes will have two genes inserted into them; a laboratory-manufactured anti-HIV gene designed to inhibit HIV reproduction (either the RevTD or Rev-TD-antiTAR gene), and a "marker" gene that will show whether or not the inserted genes have gotten into the cells. Identical twin pairs 18 years of age and older- one of whom is HIV-positive (infected with the human immunodeficiency virus) and the other HIV-negative (not infected) may be eligible for this study. All participants will have a complete medical history and physical examination, blood tests and a tetanus booster shot, if indicated. The non HIV-infected twin will then undergo lymphapheresis to collect lymphocytes. In this procedure, whole blood is collected through a needle placed in an arm vein. The blood circulates through a machine that separates it into its components. The lymphocytes are then removed, and the red cells and plasma are returned to the donor, either through the same needle or through a second needle placed in the other arm. The donor cells are grown in the laboratory for a few days, and then the new genes are inserted into them. The genetically altered cells are grown in the laboratory for several days until their numbers increase approximately a thousand-fold. They are then infused intravenously (through a vein) into the infected twin. These procedures-lymphapheresis, gene modification and infusion-will be repeated at approximately 2-month intervals up to four times. Each lymphocyte infusion takes about 60 minutes. The patient's vital signs (temperature, pulse, blood pressure and breathing) are monitored frequently during the infusion and hourly for 4 hours after the infusion. Blood samples are taken the day of the infusion, 3 days later, and then weekly to monitor the gene-modified cells, immune status, viral activity, and other factors. These tests may be done less often as the study progresses and more is learned about the safety of the infusions. The infusions are done on an outpatient basis unless side effects require that they be done in the hospital with post-infusion monitoring for at least 24 hours. Patients will be followed for long-term effects of treatment monthly for the first 3 months, once a month for the next 9 months and yearly from then on. This study will contribute information about the use and side effects of gene therapy in HIV infection that may lead to new treatment strategies. A potential direct benefit to HIV-infected individuals participating in this study is reduced viral load; in laboratory studies, the RevTD and Rev-TD-antiTAR genes have inhibited HIV spread in the test tube. However, this is an early phase of study, and the likelihood of receiving this benefit is unknown.
This study will test the effectiveness of topical thalidomide in healing mouth sores in HIV infected patients. Oral (PO) thalidomide heals these sores at a dose of 200 mg per day. However, PO thalidomide can cause drowsiness, skin rashes, allergic reactions, increased viral load, and even nerve damage that may not be reversible. This study will evaluate the efficacy of a topical formulation of thalidomide (placed directly on the surface of the sore) for the healing of these sores. Persons with HIV infection of acquired immunodeficiency of at least 18 years of age with one or more chronic, painful intraoral lesions may be eligible for this study. Subjects must be referred by a primary care physician who is managing their care, and must have HIV/AIDS status confirmed. Patients' HIV treatment regimen will not be altered and those receiving highly active therapy will not be excluded. Patients will be excluded if they are concurrently being treated for mucosal lesions (including topical or systemic steroids, viscous lidocaine, topical or systemic anti-fungals, or mouthwashes), or concurrent thalidomide therapy; receving chemotherapy or radiation therapy for neoplasms; using concurrent acute therapy for opportunistic infections; concurrent use of sedatives (such as CNS depressants or alcohol use); history of allergy to thalidomide; pre-existing peripheral neuropathy of grade II or higher; pregnant or lactating females or those not practicing contraception according to FDA guidelines for thalidomide.
We propose to conduct a multifactorial genetic study of cancer risk-related behaviors and other complex human characteristics. The main areas of interest are tobacco smoking, excess alcohol consumption, psychological traits, and HIV/AIDS susceptibility and progression. The subjects will be adult male and female probands who display one or more of the phenotypes of interest together with their brothers, sisters and parents. Information on tobacco and alcohol use, psychological and personality traits, sexual behavior, HIV status and progression, and other characteristics with possible genetic components will be obtained through structured interviews and questionnaires. DNA will be prepared from blood samples and typed for a series of candidate genes chosen for function and for random polymorphic markers. By correlating the genotypic and phenotypic information, we hope to identify individual loci that interactively contribute to many different aspects of human health and disease.
Children with symptomatic HIV-1 (Human Immunodeficiency Virus) infection are at increased risk for developing severely disabling neurological and neuropsychological deficits. HIV-1 related CNS (Central Nervous System) disease is a clinical syndrome, manifested by varying and sometimes discordant degrees of cognitive, motor and behavioral impairment. A continuum of clinical presentations attributed to the effects of HIV-1 infection on the CNS, ranging from apparently normal development, decreases in the rate of new learning to the loss of acquired skills have been observed. Two domains of psychological functioning appear most susceptible to the effects of HIV infection on the central nervous system in children: expressive behavior and attentional processes (Brouwers, et al, 1994). Attention deficits have been documented as a relative weakness on the "freedom from distractibility" subclass of IQ tests (Brouwers et al, 1989) and on behavior assessment (Moss et al, 1994). Attention, however, has many subcomponents such as focused attention, divided attention, vigilance, etc. Direct assessment of attentional functioning using reaction time has not yet been conducted and questions whether attentional components are differentially affected by the virus have not been addressed. The proposed study would assess different components of attentional functioning in children with HIV-1 disease. A quantitative and systematic method is developed that could complement the existing standardized instruments used for measuring attention and neurocognitive function in this population. Simple alerted visual reaction time will be measured with varying preparatory intervals, a two-choice reaction time in a go/no-go paradigm will be administered, and a continuous performance, divided reaction time test and an object decision task will be given. Performance on these measures will also be related to measures of brain structure and stage of HIV-1 disease.
Patients enrolled in NIH protocol 95-I-0133 at the Clinical Center may participate in an extension phase of this study in which the drug prednisone will be eliminated from the treatment regimen. Prednisone is associated with avascular necrosis, a condition that has been found in a number of patients in this study. Also, certain patients in this protocol may receive future interleukin-2 treatment cycles at home. Home administration of IL-2 injections involves less frequent data and safety monitoring and no medical evaluations at the Clinical Center except at the beginning of each cycle. To be eligible for home administration of IL-2, patients must: - Be enrolled in a current NIAID protocol for IL-2 therapy and have received at least 1 year of treatment on the protocol, with at least two well-tolerated outpatient cycles at a stable dose. - Have a history of tolerable side effects while receiving IL-2 without frequent medical interventions, intravenous fluid replacement or dose reductions. - Not have had any significant clinical or laboratory abnormalities during days 0 to 5 of the last two outpatient cycles. - Have a strong relationship with a private physician or health-care provider who has been involved in the patient's care and is willing to help supervise the patient's care during each home IL-2 cycle. - Live in a home with easy telephone access and have proved reliable in responding to telephone calls from clinic staff. - Give the clinic staff contact information for a close friend or relative who will agree to serve as a caregiver during each home cycle, providing the patient non-medical assistance and checking on his or her condition daily. - Have reasonable access to emergency medical services and a nearby medical facility. - Have proved reliable and consistent in using sterile technique, reconstituting IL-2 vials and administering subcutaneous IL-2 injections. - Be receiving outpatient IL-2 injections cycles at least once every 6 months as part of their normal protocol participation. - Have access to a home weight scale and be able to weigh themselves each day for safety monitoring. Participants will receive IL-2 cycles on the same schedule they followed in their original protocol participation. They will be seen at the Clinical Center at regularly scheduled follow-up visits between cycles and for a medical evaluation and blood drawing before the start of each cycle to determine the safety of administering the cycle. During the home cycle, the patient's case manager or other team member will place monitoring telephone calls on days 2 and 4 of the cycle and again a week later. The timing and number of these calls may change depending on the findings of ongoing assessments of their usefulness. Patients will be required to notify the study team promptly of any complications or other problems that develop with therapy.
The main objectives of this study are: 1) to determine whether various levels of severity of oral candidiasis (thrush) in the child are associated with different levels of speech production, feeding skills, and self-concept, and 2) to assess the effect of the reduction of oral thrush over time on the speech function, feeding skills, and self-concept in HIV-infected patients who already are receiving various antifungal medications for treatment of their thrush (Note: Decisions regarding antifungal therapy are made completely independent from this study). Children with HIV disease, ages 6-21 years, who have oral thrush are eligible to paricipate in the study. The child and his/her parent will be asked to complete a variety of measures at specific time intervals over approximately one month during visits to the National Institutes of Health for treatment on other protocols. First, a nurse will rate the location and severity of thrush in the child's mouth. Then the parent will complete questionnaires assessing the effect of oral thrush on the child's feeding and speech skills and everyday functioning. Finally, the child will be administered a brief speech and oral-motor evaluation and will complete some questionnaires about how the thrush affects his/her day-to-day activities and self-concept. The results of this study may help to better understand the cause of expressive language deficits observed in some children with HIV infection. More specifically, it will determine if any speech and feeding problems of HIV-infected children are associated with oral thrush. Learning more about the impact of oral thrush on the speech, feeding, and the self-concept of children with HIV disease may be used for parent and patient education and to develop rehabilitative recommendations to benefit HIV-infected patients with oral thrush.
This is a phase I/II study to determine the safety and tolerance of the protease inhibitor indinavir (MK-0639), alone and then in combination with HIV reverse transcriptase inhibitor therapy in children with HIV infection. Indinavir sulfate (the capsule formulation) has been shown to have potent antiviral activity and an acceptable safety profile in adults. HIV-infected children who have not received prior antiretroviral therapy, and children who have become refractory to prior therapy, or who have experienced toxicity to prior therapy, will be included. In addition, we will explore viral and CD4 cell kinetics before starting therapy and following exposure to antiretroviral agents. The study will be conducted in three parts. 1. In order to help interpret the antiviral activity of indinavir, the virologic and immunologic profile of children will be studied within 2 weeks prior to starting the therapeutic part. For children who have never been treated, this will be before the initiation of any antiretroviral therapy and for children who have already received antiretroviral therapy, this will be done during the initial "wash-out" phase that is routinely interposed between two different treatment regimens. 2. The initial 16 weeks of therapy will then evaluate the toxicities, pharmacokinetics, and preliminary efficacy of single drug therapy with indinavir. 3. Subsequently, all children who are able to tolerate the combination of zidovudine and lamivudine (i.e., have no prior history of intolerance to one of these two agents) will be treated with these two reverse transcriptase inhibitors in addition to the protease inhibitor indinavir. Zidovudine and lamivudine will be added after 16 weeks at a fixed dosage. Toxicity, pharmacokinetics, and preliminary efficacy of indinavir will also be investigated after combination therapy. All patients who wish to remain in this study after 96 weeks of therapy and who do not meet off study criteria will be permitted to receive extended treatment with their current indinavir combination therapy for an additional 48 weeks. The study will determine the pharmacokinetic profile of indinavir, given as single drug or in combination with zidovudine and lamivudine. It will assess the preliminary antiviral and clinical activity by monitoring clinical status, viral burden in plasma, and markers of immunologic status. Based on safety and preliminary efficacy results from studies performed in adults, we will study three dose levels which are expected to result in drug levels above the IC95 of HIV-1 for all or most of the dosing interval.
Patients with congenital or acquired immunodeficiencies are at an increased risk to develop polyclonal or oligoclonal lymphoid malignancies. Some develop a lymphoproliferative disorder that can follow a clinically aggressive course and may represent a pre-malignant lesion. Although most of these lymphoproliferative disorders are of B-cell origin, T-cell or non-B-non-T-cell processes have also been observed. The pathogenesis is only partially understood. In the case of pre-malignant conditions it is often difficult to know when and whether a therapeutic intervention is necessary and a careful consideration of potential treatment-associated morbidity is indicated. Therapies have ranged from influencing the possible infectious etiology (by treating with acyclovir), decreasing the amount of immunosuppression (in transplant patients), to the use of immunomodulatory agents, including interferons and interleukins. Recent data have indicated that the use of differentiating agents, such as the retinoids, might offer yet another treatment option. In the current study we will try to get a better understanding of the pathogenesis and natural course of lymphoproliferative disorders in immunodeficient children. The study will have two parts: an initial observation period to obtain information on the natural course of these disorders, and then a six month treatment period with the combination of a differentiating agent (13-cis-retinoic acid was used until all-trans-retinoic acid became available on 7/96) with an immunomodulatory agent (interferon-alpha2a, IFN-alpha2a).