Analysis of HIV Genetic Variation in Patients Before Beginning Highly Active Antiretroviral Therapy

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00009256
First received: January 25, 2001
Last updated: March 4, 2009
Last verified: March 2009
  Purpose

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.


Condition
HIV Infection

Study Type: Observational
Official Title: Analysis of HIV Genetic Variation in Patients Prior to Initiation of Highly Active Antiretroviral Therapy

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 65
Study Start Date: April 2000
Estimated Study Completion Date: March 2009
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

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.

EXCLUSION CRITERIA:

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).

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00009256

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00009256     History of Changes
Obsolete Identifiers: NCT00005114
Other Study ID Numbers: 000110, 00-I-0110
Study First Received: January 25, 2001
Last Updated: March 4, 2009
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Quasispecies Variation
Genotyping
Phenotyping
Antiretroviral Therapy
Drug Naive Patients
HIV
Treatment Naive

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases

ClinicalTrials.gov processed this record on October 02, 2014