HIV InfectionNCT00009256
Analysis of HIV Genetic Variation in Patients Before Beginning Highly Active Antiretroviral Therapy
An observational study of HIV Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infection
- How many people
- 65 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Apr 2000to 3 Mar 2009
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HIV infection documented by ELISA/WB.
- Viral load documented in our clinic as greater than or equal to 1000 copies RNA/ml plasma on one occasion.
- At least 18 years of age.
- For women of child-bearing potential, a negative serum pregnancy test is required within 14 days prior to enrollment.
- Able to provide written informed consent.
Who cannot join
- Absence of HIV infection within 8 weeks prior to entry, documented as a negative HIV ELISA and WB within 8 weeks of screening positive ELISA and WB.
- Use of immunosuppressants or cytotoxic agents, with the exception of corticosteroids.
- Presence of active AIDS defining opportunistic infection or malignancy requiring cytotoxic chemotherapy. Malignancies which do not require systemic cytotoxic chemotherapy, such as low grade non-progressive KS, or skin cancer treated with excision are not exclusion criteria.
- Prior antiretroviral therapy with nucleoside or non-nucleoside RT inhibitors or protease inhibitors defined as: any therapy in the last 5 years; any more than 4 days of protease inhibitors or NNRTIs ever taken; any more than 2 weeks of NRTIs ever taken.
- Psychiatric illness that in the opinion of the PI might interfere with study compliance.
- Active substance abuse or history of prior substance abuse that may interfere with protocol compliance or compromise patient safety.
- Refusal to practice safer sex practices or use precautions to prevent pregnancy (effective barrier birth control or abstinence).
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Analysis of HIV Genetic Variation in Patients Prior to Initiation of Highly Active Antiretroviral Therapy
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.
Read more
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:
- 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.
- Complete participation in this study and, if eligible, enroll in another NIH protocol (AVBIO).
- 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.
Read the 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.
- Conditions
- HIV Infection
- Keywords
- Quasispecies Variation, Genotyping, Phenotyping, Antiretroviral Therapy, Drug Naive Patients, HIV, Treatment Naive
- Medical subject headings
- HIV Infections
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2001 (estimated)
- Study start13 Apr 2000
- Study completion3 Mar 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Enrolment
- 65 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00009256
- Sponsor's protocol ID
- 000110
- Other IDs
- 00-I-0110
- Status last verified
- 3 Mar 2009
- First submitted
- 25 Jan 2001
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Barrie KA, Perez EE, Lamers SL, Farmerie WG, Dunn BM, Sleasman JW, Goodenow MM. Natural variation in HIV-1 protease, Gag p7 and p6, and protease cleavage sites within gag/pol polyproteins: amino acid substitutions in the absence of protease inhibitors in mothers and children infected by human immunodeficiency virus type 1. Virology. 1996 May 15;219(2):407-16. doi: 10.1006/viro.1996.0266.
PubMed 8638406Birk M, Sonnerborg A. Variations in HIV-1 pol gene associated with reduced sensitivity to antiretroviral drugs in treatment-naive patients. AIDS. 1998 Dec 24;12(18):2369-75. doi: 10.1097/00002030-199818000-00005.
PubMed 9875574Butto S, Argentini C, Mazzella AM, Iannotti MP, Leone P, Leone P, Nicolosi A, Rezza G. Dual infection with different strains of the same HIV-1 subtype. AIDS. 1997 Apr;11(5):694-6. No abstract available.
PubMed 9108960
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Analysis of HIV Genetic Variation in Patients Prior to Initiation of Highly Active Antiretroviral Therapy
- ClinicalTrials.gov ID
- NCT00009256
- Acronym / sponsor ID
- 000110
- Conditions
- HIV Infection
- Keywords
- Quasispecies Variation, Genotyping, Phenotyping, Antiretroviral Therapy, Drug Naive Patients, HIV, Treatment Naive
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 65 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 13 Apr 2000
- Study completion
- 3 Mar 2009
- First posted
- 26 Jan 2001 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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.
- Complete participation in this study and, if eligible, enroll in another NIH protocol (AVBIO).
- 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.
Study design
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- HIV infection documented by ELISA/WB.
- Viral load documented in our clinic as greater than or equal to 1000 copies RNA/ml plasma on one occasion.
- At least 18 years of age.
- For women of child-bearing potential, a negative serum pregnancy test is required within 14 days prior to enrollment.
- Able to provide written informed consent.
Key exclusion criteria (7 listed)
- Absence of HIV infection within 8 weeks prior to entry, documented as a negative HIV ELISA and WB within 8 weeks of screening positive ELISA and WB.
- Use of immunosuppressants or cytotoxic agents, with the exception of corticosteroids.
- Presence of active AIDS defining opportunistic infection or malignancy requiring cytotoxic chemotherapy. Malignancies which do not require systemic cytotoxic chemotherapy, such as low grade non-progressive KS, or skin cancer treated with excision are not exclusion criteria.
- Prior antiretroviral therapy with nucleoside or non-nucleoside RT inhibitors or protease inhibitors defined as: any therapy in the last 5 years; any more than 4 days of protease inhibitors or NNRTIs ever taken; any more than 2 weeks of NRTIs ever taken.
- Psychiatric illness that in the opinion of the PI might interfere with study compliance.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Background: PubMed 8638406Barrie KA, Perez EE, Lamers SL, Farmerie WG, Dunn BM, Sleasman JW, Goodenow MM. Natural variation in HIV-1 protease, Gag p7 and p6, and protease cleavage sites within gag/pol polyproteins: amino acid substitutions in the absence of protease inhibitors in mothers and children infected by human immunodeficiency virus type 1. Virology. 1996 May 15;219(2):407-16. doi: 10.1006/viro.1996.0266.
- Background: PubMed 9875574Birk M, Sonnerborg A. Variations in HIV-1 pol gene associated with reduced sensitivity to antiretroviral drugs in treatment-naive patients. AIDS. 1998 Dec 24;12(18):2369-75. doi: 10.1097/00002030-199818000-00005.
- Background: PubMed 9108960Butto S, Argentini C, Mazzella AM, Iannotti MP, Leone P, Leone P, Nicolosi A, Rezza G. Dual infection with different strains of the same HIV-1 subtype. AIDS. 1997 Apr;11(5):694-6. No abstract available.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of HIV Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00009256, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2017.