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Study of People With HIV Infection Who Have High Viral Loads Despite Combination Antiretroviral Therapy

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ClinicalTrials.gov Identifier: NCT01976715
Recruitment Status : Recruiting
First Posted : November 6, 2013
Last Update Posted : October 19, 2017
Information provided by (Responsible Party):

Study Description
Brief Summary:


- The human immunodeficiency virus (HIV) causes acquired immune deficiency syndrome (AIDS). Combination antiretroviral therapy (ART) drugs treat HIV infection. They generally decrease the amount of HIV virus in the blood (called viral load) to very low levels. This happens only if the drugs still fight HIV and if taken every day exactly as prescribed. When not taken as directed, or if the ART drugs are not strong enough, the virus can become resistant to them, and the ART will not work to control the virus. Researchers want to know how to control HIV in people who can t lower their viral load with their current ART drugs.


-<TAB>To better control HIV in people who can t get a lower viral load even with ART drugs and to learn more about why the HIV is not under control.


  • People at least 14 years old and with HIV.
  • People who have been on at least two combinations of ART drugs (including current ART).
  • People whose last two viral loads were greater than 1,000 copies/mL.


  • Participants will be screened with medical history, physical exam, and blood tests.
  • Participants will then have a baseline visit. They will have another physical exam, blood tests, plus answer questions about what they know about HIV and ART, and how they take their ART.
  • Participants will arrange to stay in the NIH hospital for 7 8 days.
  • They will take their medications as usual. At the time to take the ART drugs, they will have to ask a nurse to bring them. If they forget, the nurse will bring them.
  • Participants will meet with a doctor, pharmacist, social worker and nurse to discuss ways to help participants remember to take their drugs.
  • Participants will have blood drawn about every other day.
  • Researchers will study the test results. Some participants will be put on different ART drugs. If that happens, participants will have another NIH hospital stay for 7-8 days.
  • Participants will have 4 follow-up visits over 12 weeks, then every 3 months for 2 years or more.

Condition or disease
Acquired Immune Deficiency Syndrome Virus Acquired Immunodeficiency Syndrome Virus AIDS Virus Human Immunodeficiency Virus Human Immunodeficiency Viruses

Detailed Description:

Combination antiretroviral therapy (ART) has dramatically improved survival in individuals with human immunodeficiency virus type1 (HIV-1) infection. Despite recent development of more potent regimens with fewer toxicities and lower pill burden, there remains a subpopulation of subjects who fail to achieve and maintain viral suppression while on treatment. Factors known to contribute to virologic failure include suboptimal adherence, drug resistance, suboptimal regimen potency, sequential introduction of single drugs to a failing regimen, and reduced ART exposure due to impaired drug absorption or pharmacokinetic drug-drug interactions.

This is a natural history protocol with intensive observation intended to characterize and manage HIV-infected subjects who have documented virologic failure on their current regimen and who have experienced virologic failure in meeting one of the following criteria:

  • Documented virologic failure on at least 1 prior ART regimen and at least 2 consecutive HIV RNA plasma measurements of >1,000 copies/mL, including the last documented value, while on the current prescribed ART regimen for at least 6 months; or
  • Documented extensive resistance to at least 3 ARV drug classes, and has persistent plasma viremia (HIV RNA > 1,000 copies/mL for > 6 months) despite multiple regimen changes, regardless of how long the subject has been prescribed his or her current regimen.

We anticipate that, for a large proportion of the subjects enrolled in this protocol, nonadherence, with or without drug resistance, is the most common reason for the virologic failure. Another objective for the study is to assess the impact of a 7-day, inpatient, selfguided directly observed therapy (DOT) on HIV RNA kinetics, when subjects will receive their pre-enrollment ART regimens. During the DOT period, subjects will request their antiretroviral drugs at a pre-arranged time reflecting their home medication schedule. Failure to do so will be recorded and the medications will then be provided by the nursing staff. Adherence and psychosocial assessments will also be performed. Plasma concentrations from at least one of the antiretroviral drugs in the regimen will be measured on the first and last day of DOT to determine if suboptimal drug plasma concentration was a contributing factor to virologic failure.

Within approximately 2 weeks, but no later than 4 weeks, after DOT (post-DOT phase), the research team will review the results from the HIV-1 viral load kinetics, current and cumulative genotypic and/or phenotypic resistance tests, ART history and responses, and other identified factors that could have contributed to the treatment failure (such as concomitant medications, history of antiretroviral AEs, and psychosocial barriers). The team will then design a new, individualized treatment plan for each subject. Subjects will either continue on their pre-enrollment ART regimen, or they will receive a new, individually tailored regimen. Only FDA-approved therapeutic agents will be offered on this protocol. Subjects may be co-enrolled in an experimental protocol for optimal management of HIV disease, if one is available and eligibility criteria are met. New regimens will be monitored during a second 7-day, inpatient, self-guided DOT. Subjects will be followed after the DOT at week 2 (plus/minus 3 working days), 4 (plus/minus 3 working days), 8 (plus/minus 7 days), and 12 (plus/minus 7 days), and then every 3 months (plus/minus 2 weeks) for up to 2 years, with the option of extending participation longer if necessary. The same treatment plan may be repeated if a subject fails to respond to a new regimen.

In a select group of subjects who fail to achieve viral suppression, advanced HIV-1 variant analysis may be used to attempt to identify the presence of minority drug resistant variants. This analysis will be used as supplemental information to construct new regimens for this group of subjects. Samples of plasma, serum, and peripheral blood mononuclear cells will be stored for further evaluation of virologic evolution and other factors that may be contributing to treatment failure in this population.

Study Design

Study Type : Observational
Estimated Enrollment : 150 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Characterization and Management of Patients With HIV-1 Infection Who Experience Virologic Failure Despite Combination Antiretroviral Therapy
Study Start Date : October 30, 2013
Estimated Primary Completion Date : August 1, 2022
Estimated Study Completion Date : September 1, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
U.S. FDA Resources

Groups and Cohorts

Outcome Measures

Primary Outcome Measures :
  1. The log viral load change over time during the study enrollment period [ Time Frame: 2 years after enrollment ]

Secondary Outcome Measures :
  1. Log viral load change during the inpatient directly observed therapy period [ Time Frame: After DOT hospitalization ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   14 Years to 100 Years   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

    1. Age, greater than or equal to 14 years.
    2. Documented HIV-1 infection (prior written documentation such as positive standard ELISA or rapid HIV-1/HIV-2 antibody test with confirmatory Western Blot, or documentation of repeated HIV RNA of greater than 1,000 copies/mL)..
    3. Established care with an HIV primary care provider.
    4. Fulfilling one of the following criteria for virologic failure:

      1. Documented virologic failure on at least 1 prior ART regimen and at least 2 consecutive HIV RNA plasma measurements of greater than 1,000 copies/mL, including the last documented value, while on the current prescribed ART regimen for at least 6

        months; or

      2. Documented extensive resistance to at least 3 ARV drug classes, and has persistent plasma viremia (HIV RNA greater than 1,000 copies/mL for greater than 6 months) despite multiple regimen changes, regardless of how long the subject has been prescribed his or her current regimen.
    5. Willingness to have samples stored for future research.
    6. Willingness to undergo genetic testing.
    7. Ability and willingness to provide informed consent and be hospitalized for the inpatient DOT.


  1. HIV RNA levels at screening <1,000 copies/mL.
  2. Receiving medical care for an acute medical illness stemming from a significant comorbidity; enrollment may be deferred or postponed until the condition resolves or stabilizes.
  3. Pregnancy (if a subject becomes pregnant while enrolled in the protocol, she will continue participation throughout her pregnancy).
  4. Any illness or condition that, in the investigator s opinion, may substantially increase the risk associated with the subject s participation in the study, or may compromise the scientific objectives.
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01976715

Contact: Yolanda Mejia (240) 669-2877 yolanda.mejia@nih.gov
Contact: Alice Pau, Pharm.D. (301) 451-3740 apau@niaid.nih.gov

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL)    800-411-1222 ext TTY8664111010    prpl@mail.cc.nih.gov   
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Principal Investigator: Alice Pau, Pharm.D. National Institute of Allergy and Infectious Diseases (NIAID)
More Information

Additional Information:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01976715     History of Changes
Other Study ID Numbers: 140009
First Posted: November 6, 2013    Key Record Dates
Last Update Posted: October 19, 2017
Last Verified: July 12, 2017

Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) ):
Treatment Failure
Drug Resistance

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