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

2014-08-27 03:57:10 | BioPortfolio


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.


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



HIV Infection


National Institutes of Health Clinical Center, 9000 Rockville Pike
United States




National Institutes of Health Clinical Center (CC)

Results (where available)

View Results


Published on BioPortfolio: 2014-08-27T03:57:10-0400

Clinical Trials [318 Associated Clinical Trials listed on BioPortfolio]

The Epidemiology of Infection With Vancomycin-Resistant Enterococci

Current projects study veteran patients with chronic ulcers and MRSA colonization and infection, patients with imipenem-resistant P. aeruginosa colonization and infection, the relationship...

Diagnosis of Periprosthetic Joint Infection and the Common Pathogens, Durg-resistance in Periprosthetic Joint Infection

This retrospective study aims to improve the diagnosis of PJI as well as to identify microorganisms causing periprosthetic joint infection (PJI) and the drug-resistant spectrum

Antiretroviral Therapy for Acute HIV Infection

This is a protocol designed to provide HAART to subjects with acute HIV infection who are enrolled in SEARCH 010 study (protocol title: Establish and characterize an acute HIV infection co...

Immediate Initiation of Antiretroviral Therapy During "Hyperacute" HIV Infection

The purpose of this study is to identify and provide immediate antiretroviral therapy to a cohort of HIV-infected individuals with "hyperacute" infection (estimated date of HIV infection w...

Study of Oral Papillomavirus In Teens and Twenties

Recently human papillomavirus (HPV) has been recognized to cause some oropharyngeal (tonsil) cancer. But very little is known about oral HPV infection and risk factors. This study will eva...

PubMed Articles [6186 Associated PubMed Articles listed on BioPortfolio]

The dynamics of integration, viral suppression and cell-cell transmission in the development of occult hepatitis B virus infection.

Out of several phases of HBV infection, the least understood phase is occult hepatitis virus infection. The paucity of data due to non-availability of biological tissues and the prerequisite of ultra-...

Lymphopenia and risk of infection and infection-related death in 98,344 individuals from a prospective Danish population-based study.

Neutropenia increases the risk of infection, but it is unknown if this also applies to lymphopenia. We therefore tested the hypotheses that lymphopenia is associated with increased risk of infection a...

Pharmacological interventions for acute hepatitis C infection.

Hepatitis C virus (HCV) is a single-stranded RNA (ribonucleic acid) virus that has the potential to cause inflammation of the liver. The traditional definition of acute HCV infection is the first six ...

Predictors of certification in infection prevention and control among infection preventionists: APIC MegaSurvey findings.

The 2015 APIC MegaSurvey was completed by 4,078 members to assess infection prevention practices. This study's purpose was to examine MegaSurvey results to relate infection preventionist (IP) certific...

Motor neuron disease in patients with HIV infection: Report of two cases and brief review of the literature.

HIV-associated motor neuron disease (MND), or amyotrophic lateral sclerosis (ALS)-like syndrome associated with HIV infection, is a rare manifestation of HIV infection. HIV-associated MND has only bee...

Medical and Biotech [MESH] Definitions

Infection by a variety of fungi, usually through four possible mechanisms: superficial infection producing conjunctivitis, keratitis, or lacrimal obstruction; extension of infection from neighboring structures - skin, paranasal sinuses, nasopharynx; direct introduction during surgery or accidental penetrating trauma; or via the blood or lymphatic routes in patients with underlying mycoses.

A nontuberculous infection when occurring in humans. It is characterized by pulmonary disease, lymphadenitis in children, and systemic disease in AIDS patients. Mycobacterium avium-intracellulare infection of birds and swine results in tuberculosis.

Infection involving the tissues or organs in the PELVIS.

Infection in humans and animals caused by fungi in the class Zygomycetes. It includes MUCORMYCOSIS and entomophthoramycosis. The latter is a tropical infection of subcutaneous tissue or paranasal sinuses caused by fungi in the order Entomophthorales. Phycomycosis, closely related to zygomycosis, describes infection with members of Phycomycetes, an obsolete classification.

An infection at a specific location that may spread to another region of the body.

More From BioPortfolio on "Analysis of HIV Genetic Variation in Patients Before Beginning Highly Active Antiretroviral Therapy"

Quick Search


Relevant Topics

Pharmacy is the science and technique of preparing as well as dispensing drugs and medicines. It is a health profession that links health sciences with chemical sciences and aims to ensure the safe and effective use of pharmaceutical drugs. The scope of...

Human Immuno Deficiency Virus (HIV)
Human Immunodeficiency Virus (HIV), the causative agent of AIDS. The Human Immunodeficiency Virus, more commonly known as HIV, is a member of the lentivirus sub-set of the retrovirus family of pathogens. It causes AIDS, or Acquired Immuno Deficiency Sy...

Searches Linking to this Trial