Optimizing Treatment for Treatment-Experienced, HIV-Infected People



Status:Completed
Conditions:HIV / AIDS
Therapuetic Areas:Immunology / Infectious Diseases
Healthy:No
Age Range:16 - Any
Updated:4/21/2016
Start Date:January 2008
End Date:April 2013

Use our guide to learn which trials are right for you!

The Optimized Treatment That Includes or Omits NRTIs Trial: A Randomized Strategy Study for HIV-1-Infected Treatment-Experienced Subjects Using the cPSS to Select an Effective Regimen

The goal of anti-HIV therapy is to prevent HIV from replicating. Long-term control of HIV
requires at least two anti-HIV drugs that are active against the virus. Drug resistance is a
problem for many treatment-experienced, HIV-infected people. The purpose of this study was
to determine the benefit of adding a nucleoside reverse transcriptase inhibitor (NRTI) to a
new anti-HIV drug regimen for the suppression of HIV.

Two or more fully active antiretrovirals (ARVs) are recommended for successful suppression
of HIV. In people infected with resistant HIV virus, finding two drugs that are fully active
against HIV can be a challenge. However, the new generation of anti-HIV drugs has been
designed to suppress drug-resistant HIV. These drugs include the FDA-approved protease
inhibitors (PIs) darunavir and tipranavir, the investigational non-nucleoside transcriptase
inhibitor (nNRTI) etravirine, the FDA-approved fusion inhibitor enfuvirtide, the recently
FDA-approved CCR5 inhibitor maraviroc, and the investigational integrase inhibitor
raltegravir. Also, it is not yet known whether multiple, partially-active drugs have the
same rate of success in suppressing HIV. The purpose of this study was to use HIV resistance
testing to predict the potency of a suggested ARV regimen using second generation ARVs and
determine if the benefits of adding NRTIs to this new drug regimen outweigh the risks of
drug toxicity and pill burden. All participants had treatment experience or resistance to
NRTIs, nNRTIs, and PIs, and received novel agents.

An active screening period (after enrollment but before randomization or treatment
dispensation), occurred for up to 75 days for all participants, and study participation
lasted an additional 96 weeks for those who qualified for either randomization or assignment
(i.e. not randomized), to the study intervention. During active screening, all participants
remained on their current drug regimen. During screening, phenotypic and genotypic HIV
resistance tests were performed on participants' blood samples, as well as a coreceptor
tropism assay. Using this information and medication history, the study team determined the
best new regimen options for each participant. Each clinician, along with the study
participant, then chose a new regimen based on the recommendations of the study team and the
participant's preference.

Evaluation for study outcomes began when participants started their new regimen as assigned
by either randomization or determined assignment. Stratification between Arms A (Add NRTIs)
and B (Omit NRTIs) or Arm C (Non-randomized to Add NRTIs) was based on predicted activity of
the new regimen. Those assigned to a regimen with higher predicted activity were randomly
assigned to Arm A (Add NRTIs) or B (Omit NRTIs); those assigned a regimen predicted to have
lower activity were not randomized, but were assigned to Arm C (Add NRTIs).

Participants in Arms A and C were instructed to take their newly assigned study regimen plus
at least 2 NRTIs (personalized from expert recommendation and choice by local provider and
participant) for 96 weeks. Participants in Arm B were instructed to take their newly
assigned study regimen with no NRTIs for 96 weeks. Participants in all arms who met the
primary efficacy outcome of regimen failure remained in the study in order to be followed
for important secondary outcomes.

All participants were scheduled to have 13 clinical visits, which included blood collection.
At some visits, urine collection and quality of life and adherence questionnaires occurred.
A neurocognitive assessment was performed for all participants at time of starting the new
study regimen. Participants may also have consented to have cerebrospinal fluid collected
via lumbar puncture following study treatment assignment and/or at Week 24. Those
participants who consented to cerebrospinal fluid collection also had neurocognitive
assessments at the times of collections. Participants were responsible for obtaining certain
ARVs not provided by the study, including the ARVs they during the active screening period.

The primary and secondary study objectives and comparisons relate to the randomized arms,
and therefore, results are not provided for the non-randomized arm (C). The purpose of the
non-randomized arm (C) was to include persons higher baseline resistance (and thus, lower
activity scores) in order to address an exploratory objective related to the predictive
power of these activity scores (and thus a larger range of scores by inclusion of arm C), on
certain, virologic outcomes.

Inclusion Criteria:

- HIV-1 infection

- Triple-class drug experience or resistance. More information on this criterion can be
found in the protocol.

- Currently on a failing PI-containing regimen that includes 2 other ARVs with no
regimen change for 8 weeks prior to study screening

- HIV viral load of 1000 copies/ml or more

- Hepatitis B surface antigen negative within 90 days of study entry

- Able to obtain NRTIs and ritonavir and have required ARVs at time of starting study
intervention

- Willing to use acceptable forms of contraception

- Parent or legal guardian willing to provide consent, if applicable

- CD4 count result from a specimen drawn within 120 days prior to study entry

- If any previous HIV-1 viral co-receptor tropism result is available, then most recent
specimen date and the tropism result of that specimen AND specimen date and tropism
result of any test with either X4 or D/M result, if different from the first
specimen, must be available

Inclusion Criteria continued:

- Receipt of successful phenotype/genotype resistance results within 105 days prior to
study treatment intervention assignment

- Study team identification of a study regimen and at least 2 NRTIs for participant to
take

- Certain abnormal laboratory values. More information on this criterion can be found
in the protocol.

Exclusion Criteria:

- Chronic, active hepatitis B virus infection (hepatitis B surface antigen positive or
HBV DNA positive)

- Taking certain medications. More information on this criterion can be found in the
protocol.

- Known allergy/sensitivity to components of two or more of the study-provided drugs or
their formulations. For maraviroc, this includes hypersensitivity or history of
allergy to soy lecithin or peanuts.

- Active drug or alcohol use that, in the opinion of the investigator, may interfere
with the study

- Pregnancy or breastfeeding

- Use of any immunomodulator (interferons, interleukins, systemic corticosteroids, or
cyclosporine), vaccine, or investigational therapy within 30 days prior to study
treatment allocation/assignment

- Require certain medications prohibited with study treatment

- Serious illness requiring systemic treatment or hospitalization. Participants who
complete therapy or are clinically stable on therapy for at least 14 days prior to
study treatment allocation are not excluded.
We found this trial at
62
sites
Nashville, Tennessee 37204
?
mi
from
Nashville, TN
Click here to add this to my saved trials
1650 Grand Concourse
Bronx, New York 10457
?
mi
from
Bronx, NY
Click here to add this to my saved trials
2311 NW Northrup St # 105
Portland, Oregon 97210
?
mi
from
Portland, OR
Click here to add this to my saved trials
Atlanta, Georgia 30308
?
mi
from
Atlanta, GA
Click here to add this to my saved trials
Aurora, Colorado 80045
?
mi
from
Aurora, CO
Click here to add this to my saved trials
Baltimore, Maryland 21201
?
mi
from
Baltimore, MD
Click here to add this to my saved trials
Baltimore, Maryland 21287
?
mi
from
Baltimore, MD
Click here to add this to my saved trials
Birmingham, Alabama 35294
?
mi
from
Birmingham, AL
Click here to add this to my saved trials
Boston, Massachusetts 02114
?
mi
from
Boston, MA
Click here to add this to my saved trials
?
mi
from
Boston, MA
Click here to add this to my saved trials
Boston, Massachusetts 02118
?
mi
from
Boston, MA
Click here to add this to my saved trials
?
mi
from
Boston, MA
Click here to add this to my saved trials
Boston, Massachusetts 02215
?
mi
from
Boston, MA
Click here to add this to my saved trials
Camden, New Jersey 08103
?
mi
from
Camden, NJ
Click here to add this to my saved trials
Chapel Hill, North Carolina 27599
?
mi
from
Chapel Hill, NC
Click here to add this to my saved trials
Chicago, Illinois 60611
?
mi
from
Chicago, IL
Click here to add this to my saved trials
Chicago, Illinois 60612
?
mi
from
Chicago, IL
Click here to add this to my saved trials
Cincinnati, Ohio 45219
?
mi
from
Cincinnati, OH
Click here to add this to my saved trials
Cleveland, Ohio 44106
?
mi
from
Cleveland, OH
Click here to add this to my saved trials
Cleveland, Ohio 44109
?
mi
from
Cleveland, OH
Click here to add this to my saved trials
Columbus, Ohio 43210
?
mi
from
Columbus, OH
Click here to add this to my saved trials
?
mi
from
Dallas, TX
Click here to add this to my saved trials
Denver, Colorado 80204
?
mi
from
Denver, CO
Click here to add this to my saved trials
Detroit, Michigan 48201
?
mi
from
Detroit, MI
Click here to add this to my saved trials
Detroit, Michigan 48202
?
mi
from
Detroit, MI
Click here to add this to my saved trials
Durham, North Carolina 27710
?
mi
from
Durham, NC
Click here to add this to my saved trials
Houston, Texas 77030
?
mi
from
Houston, TX
Click here to add this to my saved trials
Houston, Texas 77030
?
mi
from
Houston, TX
Click here to add this to my saved trials
?
mi
from
Long Beach, CA
Click here to add this to my saved trials
Los Angeles, California 90033
?
mi
from
Los Angeles, CA
Click here to add this to my saved trials
Los Angeles, California 90033
?
mi
from
Los Angeles, CA
Click here to add this to my saved trials
Los Angeles, California 90035
?
mi
from
Los Angeles, CA
Click here to add this to my saved trials
?
mi
from
Los Angeles, CA
Click here to add this to my saved trials
?
mi
from
Memphis, TN
Click here to add this to my saved trials
?
mi
from
Miami, FL
Click here to add this to my saved trials
New Orleans, Louisiana 70112
?
mi
from
New Orleans, LA
Click here to add this to my saved trials
New York, New York 10011
?
mi
from
New York, NY
Click here to add this to my saved trials
New York, New York 10016
?
mi
from
New York, NY
Click here to add this to my saved trials
New York, New York 10016
?
mi
from
New York, NY
Click here to add this to my saved trials
New York, New York 10029
?
mi
from
New York, NY
Click here to add this to my saved trials
New York, New York 10032
?
mi
from
New York, NY
Click here to add this to my saved trials
New York, New York 10032
?
mi
from
New York, NY
Click here to add this to my saved trials
New York, New York 10037
?
mi
from
New York, NY
Click here to add this to my saved trials
?
mi
from
Newark, NJ
Click here to add this to my saved trials
Newark, New Jersey 07103
?
mi
from
Newark, NJ
Click here to add this to my saved trials
Palo Alto, California 94304
?
mi
from
Palo Alto, CA
Click here to add this to my saved trials
Philadelphia, Pennsylvania 19104
?
mi
from
Philadelphia, PA
Click here to add this to my saved trials
Philadelphia, Pennsylvania 19107
?
mi
from
Philadelphia, PA
Click here to add this to my saved trials
Pittsburgh, Pennsylvania 15213
?
mi
from
Pittsburgh, PA
Click here to add this to my saved trials
?
mi
from
Providence, RI
Click here to add this to my saved trials
?
mi
from
Richmond, VA
Click here to add this to my saved trials
Rochester, New York 14607
?
mi
from
Rochester, NY
Click here to add this to my saved trials
Rochester, New York 14642
?
mi
from
Rochester, NY
Click here to add this to my saved trials
San Diego, California 92103
?
mi
from
San Diego, CA
Click here to add this to my saved trials
San Francisco, California 94110
?
mi
from
San Francisco, CA
Click here to add this to my saved trials
San Francisco, California 94143
?
mi
from
San Francisco, CA
Click here to add this to my saved trials
?
mi
from
San Juan,
Click here to add this to my saved trials
Seattle, Washington 98104
?
mi
from
Seattle, WA
Click here to add this to my saved trials
?
mi
from
St. Louis, MO
Click here to add this to my saved trials
Washington, District of Columbia 20007
?
mi
from
Washington,
Click here to add this to my saved trials
Washington, District of Columbia 20010
?
mi
from
Washington,
Click here to add this to my saved trials
Washington, District of Columbia 20060
?
mi
from
Washington,
Click here to add this to my saved trials