Ignite Creation Date:
2025-12-24 @ 11:17 PM
Ignite Modification Date:
2025-12-27 @ 11:23 PM
Study NCT ID:
NCT00009256
Status:
COMPLETED
Last Update Posted:
2017-07-02
First Post:
2001-01-25
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Analysis of HIV Genetic Variation in Patients Before Beginning Highly Active Antiretroviral Therapy
Sponsor:
National Institute of Allergy and Infectious Diseases (NIAID)
Organization:
Study Overview
Official Title:
Analysis of HIV Genetic Variation in Patients Prior to Initiation of Highly Active Antiretroviral Therapy
Status:
COMPLETED
Status Verified Date:
2009-03-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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.
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.
Detailed Description:
Infection with human immunodeficiency virus (HIV) results in progressive immune destruction and death. Current therapy for HIV (highly active antiretroviral therapy or HAART) infection utilizes combinations of drugs that, under optimum conditions, inhibit HIV replication, halt progressive immunodeficiency, and permit a measure of immunological reconstitution. In its present form, however, HAART is inadequate. HAART does not cure HIV infection, and has significant adverse side effects, which may require drug discontinuation. One of the most challenging limitations of HAART is the development of drug resistance, which may occur in 30-40% of treated patients. The precise mechanisms responsible for drug resistance remain uncertain, but explanations include the emergence of HIV variants encoding genetic mutations that confer resistance to antiretroviral drugs. Such drug resistant mutations may occur and be present at low frequencies prior to drug therapy. Understanding how these mutations arise and remain circulating in populations of HIV is uncertain.
The purpose of the present protocol is to derive a comprehensive description of HIV population genetics in a longitudinal, observational study of HIV-infected patients prior to initiating antiretroviral therapy. We plan to utilize frequent blood sampling and an extensive sequencing strategy to investigate parameters of HIV population genetics, including: a) genotypic and phenotypic analyses of HIV drug resistance mutations, b) determinations of the rates at which mutations arise, become fixed, lost, or undergo recombination, c) linkage analyses, d) estimates of the size of the effective virus population. We plan to apply this information to develop models of HIV evolution, predict the genetic behavior of HIV populations, including the emergence of resistant genomes. We expect that information regarding HIV population genetics may assist in designing appropriate drug regimens to salvage control of HIV virus replication after initial regimens have failed.
The purpose of the present protocol is to derive a comprehensive description of HIV population genetics in a longitudinal, observational study of HIV-infected patients prior to initiating antiretroviral therapy. We plan to utilize frequent blood sampling and an extensive sequencing strategy to investigate parameters of HIV population genetics, including: a) genotypic and phenotypic analyses of HIV drug resistance mutations, b) determinations of the rates at which mutations arise, become fixed, lost, or undergo recombination, c) linkage analyses, d) estimates of the size of the effective virus population. We plan to apply this information to develop models of HIV evolution, predict the genetic behavior of HIV populations, including the emergence of resistant genomes. We expect that information regarding HIV population genetics may assist in designing appropriate drug regimens to salvage control of HIV virus replication after initial regimens have failed.
Study Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 00-I-0110 | None | None | View |