View clinical trials related to HIV Infection.
Filter by:It is estimated that the VHA is caring for nearly 40 percent of all HIV-infected veterans. To benefit from recent improvements in anti-HIV therapy, patients need to take their medications consistently.
Complementary and alternative medicines are widely used in the HIV-infected population. Recent data have shown serious drug interactions between certain complementary medicines and protease inhibitors. Silymarin (Milk thistle) is a commonly used dietary supplement in HIV-infected patients for treatment of hepatitis or as a hepato-protectant. Data are available suggesting that it may alter cytochrome P4503A4-mediated drug metabolism. To evaluate the effect of milk thistle on the protease inhibitor, indinavir (IDV), ten healthy subjects will receive IDV (Crixivan) alone and in combination with an over-the-counter silymarin preparation. IDV will initially be administered alone at a dose of 800 mg Q8H for four doses and serial samples will be collected for determination of IDV pharmacokinetics after the morning dose on day 2. Subjects will then initiate therapy will milk thistle using a standardized formulation and dose for three weeks after which subjects will then again take 4 doses of IDV and have serial samples collected for IDV plasma concentrations. There will then be a 11-day washout period with no drugs, after which IDV will again be given for 4 doses and samples will be collected evaluate the offset of the effects of milk thistle. To examine the effect of milk thistle on other CYP450 pathways, subjects will receive a single dose of caffeine and dextromethorphan and have urine collected before and after milk thistle, and after the washout period. Indinavir, caffeine, and dextromethorphan concentrations in plasma or urine will be determined using validated HPLC methods. Steady-state noncompartmental parameters of indinavir in the presence and absence of milk thistle will be determined. Pharmacokinetic parameters will be compared using ANOVA that will include factors for a period effect and a treatment effect. Statistical analyses will include calculation of the mean ratio of the AUC in the treatment phases compared to IDV alone and determination of 95% confidence intervals. This study will help define the drug interaction potential of complementary and alternative therapies in HIV-infected patients.
The purpose of this study is to gain knowledge about why drug therapy sometimes stops working in people infected with the human immunodeficiency virus (HIV). This occurs in 30 to 40% of patients treated with powerful antiretroviral drugs. The study will examine how the virus becomes resistant to drug treatment through mutations (changes) and how different mutations produce new variants that are resistant to more than one drug. HIV-infected patients 18 years and older who have not been treated with antiretroviral medications and who have a relatively stable amount of virus in their blood (viral load) may be eligible for this study. Pregnant or breastfeeding women may not participate. Candidates will be screened with blood tests to determine viral load and to study the genetics of the virus. Participants will be hospitalized at the NIH Clinical Center for 10 days for daily blood sampling. (In exceptional circumstances, the sampling may be done on an outpatient basis.) After discharge, patients will be followed by weekly visits for blood tests for a total of 120 days. When antiretroviral treatment begins, the patient may do one of the following: 1. Continue on this study with antiretroviral treatment. Therapy will consist of D4T, 3TC, and efavirenz. Other drugs may be substituted for any of these that cannot be tolerated. HIV protease inhibitors will not be included in the regimen. 2. Complete participation in this study and, if eligible, enroll in another NIH protocol (AVBIO). 3. Begin standard antiretroviral therapy with a private physician. Patients for whom treatment is not yet recommended or who choose not to be treated may continue to be monitored with blood tests for a total of 18 months. (Patients who leave the study after this time may re-join when they decide to start treatment.) Participants may also undergo the following optional procedures to study the genetic variation of HIV: lymph node biopsy, spinal tap, and semen donation or female genital washing to collect secretion samples. Sexual partners or needle-sharing partners of study patients are invited to enroll in this study to provide blood samples at the time the patient enrolls and at two intervals after any needle sharing or unsafe sex event they may report to NIH. Partners may also donate genital secretions or semen, and a lymph node or spinal fluid sample. Information from this study may help in the development of new drug treatments that will be effective in controlling HIV infection when other treatments no longer work.
This study will examine the safety and effectiveness of renal (kidney) transplantation for HIV-infected patients with end-stage renal disease (kidney failure). Although kidney transplant is the best treatment for most causes of kidney failure, people infected with HIV are not offered this procedure because the immunosuppressive drugs (drugs that suppress immune function) required to prevent organ rejection could further impair the patient's already weakened immune system. This study will use a regimen of immunosuppressants designed to complement treatment for patients taking highly active antiretroviral therapy (HAART). HIV-infected patients between 18 and 60 years of age with renal failure who have not had any opportunistic infections for 5 years may be eligible for this study. Candidates will be screened with a medical history, physical examination, and blood and urine tests. Before the transplant procedure, participants will undergo additional tests and procedures, including blood studies, 24-hour urine collection, infectious disease consultation, tuberculin skin test, PAP smear for women, chest X-ray, brain and hip MRI studies and DEXA-scan to evaluate bone density. In addition, patients may undergo leukapheresis to obtain white blood cells for study. For this procedure, whole blood is drawn through a needle in an arm vein and passed through a cell separator machine. The white cells are collected for removal, and the rest of the blood is returned to the body through the same needle or another needle in the other arm. When a donor organ becomes available for transplant, the patient will receive three anti-rejection drugs-cyclosporine, mycophenolate mofetil and prednisone-to prevent organ rejection. Immediately after the surgery, HAART drugs will be stopped for 7 days until stable levels of the immune suppressants can be achieved. Then, HAART will be re-started and all medications will be adjusted to achieve adequate blood levels. Patients must stay in the local area 60 days after discharge from the hospital for monitoring. Frequent blood samples will be taken to monitor kidney function, viral load and CD4+ T cell counts. Follow-up visits will then be scheduled monthly for the first 6 months after transplant, then every other month for 1 year. Kidney biopsies will be done at the end of the first month, after 6 months, and yearly for 5 years. For the biopsy, a special needle is used to remove a small piece of kidney tissue for microscopic examination. The biopsies and blood tests are done to evaluate the immune response to the transplanted organ and to study how HAART interacts with the immune suppressing drugs.
This study will test the safety, side effects and anti-HIV activity of different doses of capravirine in children and adolescents with HIV infection. Capravirine belongs to a class of drugs called non-nucleoside reverse transcriptase inhibitors (NNRTIs), which prevent the virus from replicating (making more copies of itself). Other NNRTIs are nevirapine, delavirdine and efavirenz. HIV-infected children between the ages of 4 months and 21 years may be eligible for this study if they: 1) have received less than 6 weeks of treatment with antiretroviral drugs; 2) have not benefited from antiretroviral therapy after 12 weeks of treatment; 3) cannot continue antiretroviral treatment because of harmful side effects. For the first week of the study, participants will have a 1-week "washout period" in which they will receive no anti-HIV therapy. During this time, they will have physical, eye and neuropsychologic examinations, blood and urine tests, echocardiogram, electrocardiogram (EKG), chest X-ray, head CT scan and skin tests. These physical exams and tests will be repeated throughout the study to determine changes in health. After the washout period, patients will take capravirine once a day in the morning for 6 days. After each dose, a small amount of blood will be drawn at 8 different times over 12 hours to measure the activity of the drug and HIV blood levels. A heparin lock will be placed in the vein to avoid multiple needlesticks. After the 6 days of capravirine there will be another washout period, this time for 21 days. During this time, doctors will determine the optimum combination therapy for the individual patient. After the second washout, patients will begin combination therapy with capravirine plus at least two other anti-HIV medicines. (These may include a reverse transcriptase inhibitor such as zidovudine, didanosine, lamuvidine, zalcitabine, or stavudine, and maybe one or more protease inhibitors such as ritonavir, nelfinavir, saquinavir, indinavir or amprenavir.) For the first week, patients will have a daily blood test to determine HIV blood levels. Afterwards, treatment will continue on an outpatient basis with clinic visits every 4 to 8 weeks for physical exams, lab tests and other procedures as required. The study will last approximately 48 weeks. Patients who benefit from capravirine therapy may be able to continue to receive the drug from the drug company sponsor or as part of another study, or the protocol for this study may be amended to lengthen the treatment period.
The purpose of this study is to determine how laboratory tests called genotyping and phenotyping assess the effectiveness of antiretroviral drugs used to treat HIV infection. Some HIV-infected patients have measurable levels of virus in their blood even though they are taking combination drug therapy-including didanosine, stavudine, or efavirenz-against HIV. Genotyping and phenotyping can be used to test for resistance to a specific drug, thereby providing information that can help doctors decide on optimal drug treatment for a given patient. Genotyping identifies mutations, or changes, the virus undergoes that allow it to continue to grow despite drug treatment. Phenotyping involves growing the virus in test tubes with different amounts of drug and then calculating how much drug is required to stop its growth. Patients 18 years of age and older with HIV infection and viral levels between 5000 and 100,000 copies per milliliter of blood who have been taking antiretroviral therapy for at least 6 months may be eligible for this study. Candidates will be screened with a urine test and various blood tests, including genotyping and phenotyping. Participants will have a series of tests to determine whether or not a drug is active against HIV. This involves temporarily stopping the drug under study (i.e., either efavirenz or didanosine or stavudine). The study procedure is as follows: 1. Patients will have six blood tests over 10 days to measure viral load while on all current anti-HIV medications. On one of those days two blood tests will be done to measure levels of didanosine or stavudine. Efavirenz will also be measured if this drug is to be stopped. 2. The patient will temporarily stop the drug under while continuing to take the other drugs. (Efavirenz will be stopped for 3 weeks; stavudine and didanosine will be stopped for 2 weeks.) Seven blood tests will be done at the following intervals to measure viral load: For patients who stop efavirenz, blood will be drawn on days 13, 18, 20, 22, 24,28 and 30. (Day 0 is the first day of the study.) Patients who stop stavudine or didanosine will have blood drawn on days 11, 13, 15, 17, 19, 22 and 24. Repeat genotype and phenotype testing will also be done during this time, and a CD4 count (measurement of a certain type of white blood cell) will be done at the end of this 2- or 3-week period. 3. The drug that was stopped will be restarted and viral load tests will be repeated. For pati...
This study will determine if blood levels of anti-HIV drugs in pregnant women change at different stages of pregnancy and if these changes require dosage adjustments in order to maintain adequate drug levels during pregnancy. Anti-HIV medications are recommended for HIV-infected women during pregnancy not only to treat their infection, but also to reduce the chance of passing the virus to the baby during pregnancy. Changes in the body that occur during pregnancy may affect how the body uses and eliminates these drugs, reducing their levels during pregnancy. Pregnant women 18 years of age or older who are infected with HIV may be eligible for this study. Candidates will have a medical history and physical examination, pregnancy test and blood tests. Participants will come to the NIH Clinical Center once every 6 to 12 weeks until around their 34th week (8 months) of pregnancy and then again at least 1 month after the birth of the baby to have blood drawn. A catheter (thin plastic tube) will be placed in a vein to avoid multiple needle sticks for blood sampling during the day. The first sample will be collected before the patient takes the morning doses of anti-HIV medicines and additional samples will be drawn at 1, 2, 4, 8 and 12 hours after taking the medication. A urine sample will also be collected at each visit.
This study will investigate the safety and effectiveness of a new stem cell transplant procedure to treat acute or chronic leukemia, multiple myeloma, myelodysplastic syndrome, Hodgkin's and non-Hodgkin's lymphoma in HIV-infected patients. HIV-infected patients usually are not offered bone marrow transplant treatments because they are at increased risk of dying from the intense chemotherapy and radiation therapy used for the procedure. This study uses a modified procedure, transplanting stem cells instead of bone marrow, designed to be less dangerous for such patients. Patients will also undergo a procedure called gene transfer to try to halt progression of their HIV infection. The procedure in this study differs from standard bone marrow transplantation in three ways: Stem cells will be transplanted instead of bone marrow. (Stem cells, which are produced by the bone marrow, mature into the different blood components-white and red cells and platelets.) The stem cell donor will be given a drug that releases these cells from their bone marrow into the blood stream. The cells will then be collected from the donor by apheresis, a procedure in which whole blood is drawn, the stem cells separated and removed, and the rest of the blood returned to the donor.); The procedure will use lower doses of chemotherapy than the conventional method, and will not use radiation therapy; or A laboratory-manufactured gene designed to obstruct HIV reproduction will be inserted into the stem cells, rendering future cells that develop from resistance to the virus. Prospective patients will be tested for matching with an HIV-negative donor (family member) and will undergo a medical history, physical examination and several tests (e.g., breathing tests, X-rays, etc.) to determine eligibility for the study. Study participants will then undergo apheresis to collect white blood cells called lymphocytes. Stem cells will be collected from the donor. Half the donated cells will have the HIV-resistant gene inserted; the other half will have a "control" gene inserted. Additional stem cells collected a second day will not be manipulated. All the donor cells will be frozen until transplantation. Patients will be given drugs (cyclophosphamide, fludarabine and cyclosporin) to prevent the donated cells from being rejected and to prevent them from damaging the patient's organs. The thawed stem cells will then be infused through a vein. After 30, 60 and 100 days, bone marrow cells and circulating lymphocytes will be checked to see how many are of donor cell origin. If less than 100 percent are of donor origin, more lymphocytes will be transfused. Patients will have physical examinations and blood tests once or twice a week for 2 to 3 months with and then will be followed periodically for at least 5 years.
This 2-part study will test the safety and anti-HIV activity of capravirine alone, and the safety, anti-HIV activity, and drug interactions of capravirine combined with other anti-HIV drugs. Capravirine belongs to a class of drugs called non-nucleoside reverse transcriptase inhibitors (NNRTIs), which are effective when used together with other drugs, including nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors. Normal volunteers 18 years of age and older may enroll in Part 1 of the study. HIV-infected patients 18 years of age and older who have not previously been treated with a NNRTI (efavirenz, nevirapine, and delavirdine) may participate in Part 2. All prospective study participants will be screened for eligibility with a physical examination, blood tests, a urine test and an electrocardiogram (ECG). Part 1 - Volunteers will be randomly assigned to one of two treatment groups as follows: Group 1 will receive capravirine alone for 7 days and capravirine plus efavirenz (another NNRTI) for an additional 10 days. On day 1, participants will have a physical examination, urine test and laboratory blood tests. Blood samples will be collected just before the first dose of capravirine is given and again at 0.5, 1, 2, 4, 6, 8 and 12 hours after the dose. A small plastic tube will be placed in a vein to avoid multiple needle sticks. On day 8, participants will have another physical examination and laboratory blood tests. Blood samples will be drawn again as described above. In the evening of day 8, efavirenz will be added to the regimen. On day 18 (the last day of the study), participants will have another physical examination and blood tests. Blood will again be collected as described above. Group 2 will take capravirine alone for 8) days and capravirine plus ritonavir (a protease inhibitor) for an additional 8 days. Physical examinations, urine tests, and blood collections will be done as described above on day 1, day 8 and day 16 (the last day) of the study. Part 2 - Patients will take capravirine alone for 7 days. On day 1, patients will have a physical examination, urine test and laboratory blood tests. Blood samples will be collected just before the first dose of capravirine is given and again at 0.5, 1, 2, 4, 6, 8 and 12 hours after the dose. A small plastic tube will be placed in a vein to avoid multiple needle sticks. On day 8, patients will have another physical examination and laboratory blood tests. Blood samples will be drawn again as described above. Additional drugs will then be added to the regimen (in varying doses according to group), as follows: Group 1 - efavirenz plus abacavir Group 2 - ritonavir plus efavirenz plus abacavir Group 3 - ritonavir plus efavirenz plus abacavir On day 15, the procedures performed on day 8 will be repeated. Patients will have the option of having blood drawn daily on days 2 through 7 to measure HIV-1 viral load and of having a lumbar puncture (spinal tap) done between days 2 and 7 to measure how well capravirine gets into the central nervous system. After day 15, patients in all groups will continue with their drug regimen until week 48 or until it is determined that the treatment is not effective for the patient. Physical examinations, viral load measurements, white blood cell counts and other blood tests will be done periodically throughout the trial. Within 4 weeks after the end of the study, patients will be followed with another physical examination, blood and urine tests, and an ECG.
This study will evaluate the accuracy of an experimental test method called nucleic acid amplification technology (NAT) in detecting human immunodeficiency virus (HIV) and hepatitis C virus (HCV). This test amplifies the nucleic acid in a virus more than a million-fold, allowing early detection of minute quantities of virus in the blood. Blood donors to the National Institutes of Health's Department of Transfusion Medicine (blood bank) will have their blood screened with transcription mediated amplification, a type of NAT test. Donors whose blood is found positive for HIV or HCV by NAT testing will be notified and asked to participate in this study. Those who agree will provide a blood sample about once a week for 3 months. The samples will be tested with additional assays to detect evidence of HIV or HCV infection. If the test results are confirmed positive, no more blood samples will be collected. The results of the tests and their significance will be explained to participants. It is anticipated that NAT screening will reduce the risk of transfusion-related HIV transmission from the current 1 in 650,000 to 1 in a million and the risk of HCV transmission from the current 1 in 100,000 to 1 in 350,000. It is possible that these tests will completely eliminate the risk of transmitting these diseases through blood transfusion.