HIV InfectionsNCT00051831
Effect of an Enfuvirtide-based Anti-HIV Drug Regimen on Latent HIV Reservoirs in Treatment Naive Adults
A study testing Emtricitabine, Enfuvirtide and Ritonavir in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 7 sites in 2 countries.
Trial summary
HIV replication in resting CD4 cells is so minimal that anti-HIV drugs often fail to destroy the virus in these cells. Enfuvirtide, also known as T-20, is a type of anti-HIV drug called a fusion inhibitor. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infections
- What is being tested?
- Emtricitabine, Enfuvirtide and Ritonavir
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 7 sitesin 2 countries
- Study dates
- Oct 2003to May 2008
- Phase
- Interventional
- 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-1 infected
- Viral load of 1,000 copies/ml or greater within 60 days prior to study entry
- CD4 count of 100 cells/mm3 or greater within 60 days prior to study entry
- Willing to use acceptable methods of contraception
Who cannot join
- Previous treatment with any nucleoside analogue, nonnucleoside reverse transcriptase inhibitor, or fusion inhibitor for longer than 7 days
- Any previous treatment with T-20, lamivudine, or FTC
- HIV-related vaccine within 6 months prior to study entry
- Evidence of HIV seroconversion within 6 months prior to study entry
- Acute AIDS-defining opportunistic infection (OI). Patients who are not clinically stable or who have not been on therapy for the OI for at least 30 days prior to study entry are excluded. Patients who have no evidence of active disease and have been receiving maintenance therapy for AIDS-related OI for at least 30 days are not excluded.
- Systemic chemotherapy within 30 days of study entry or anticipated need for systemic chemotherapy before the end of the study
Show all 11Show fewer
- Treatment with immune modulators such as systemic steroids, IL-2, alpha interferon, G-CSF, erythropoietin, or any investigational agent within 30 days of study entry
- Allergy to study drugs or their formulations
- Serious illness, substance abuse, or other medical condition that would compromise the patient's ability to participate in the study
- Certain primary resistance HIV mutations
- Pregnancy or breastfeeding
Trial locations and contacts
7 sites in 2 countries.
7 sites in 2 countries
United States6 sites
University of Colorado Hospital CRS
Aurora, Colorado, 80262-3706
Massachusetts General Hospital ACTG CRS
Boston, Massachusetts, 02114
Unc Aids Crs
Chapel Hill, North Carolina, 27514
The Ohio State Univ. AIDS CRS
Columbus, Ohio
NY Univ. HIV/AIDS CRS
New York, New York, 10016-6481
Washington U CRS
St Louis, Missouri, 63108-2138
About this study
Official title: A Pilot Study to Measure the Clearance of Replication-Competent HIV-1 in Resting Memory CD4+ Cells in HIV-1-Infected Subjects Who Receive Enfuvirtide Plus Oral Combination Antiretroviral Therapy
HIV replication in resting CD4 cells is so minimal that anti-HIV drugs often fail to destroy the virus in these cells. Enfuvirtide, also known as T-20, is a type of anti-HIV drug called a fusion inhibitor. The purpose of this study is to test the ability of a T-20-enhanced treatment regimen to decrease the number of resting CD4 cells that become infected with HIV.
Read the detailed description
While current HIV treatment with combination antiretroviral therapy (ART) has reduced morbidity and mortality, it does not eradicate or cure HIV infection. A possible explanation for this failure is the persistence of virus in long-lived reservoirs. Resting memory CD4 cells have been proposed as providing a cellular reservoir. Most patients who initiate ART during chronic HIV-1 infection do not experience a detectable reduction in HIV in the latent reservoir; this may be due to low levels of ongoing viral replication that maintains the resting CD4 cell reservoir. Increasing the potency of therapy by inhibiting new viral targets may result in a decrease in the number of latently infected cells and clearance of the latent reservoir. Addition of the fusion inhibitor T-20 to ART including reverse transcriptase inhibitors and protease inhibitors (PIs) may help achieve this goal. This study will evaluate whether treatment naive, chronically infected HIV patients treated with T-20 plus emtricitabine (FTC), ritonavir (RTV), saquinavir (SQV), and tenofovir disoproxil fumarate (TDF) have a measurable decline in the latently infected CD4 cell reservoir. Patients and their physicians may choose different PIs than RTV and SQV, but they will not be provided by the study.
Patients in this study will receive injections of T-20 twice daily in addition to oral FTC and TDF once daily and oral RTV and SQV twice daily. At Week 24, patients will have their latent cell reservoir sampled. Patients whose HIV viral loads are less than 50 copies/ml at or after Week 24 but prior to Week 48 will continue the treatment regimen through the end of the study; their latent cell reservoirs will be tested at Weeks 48, 72, and 96. Patients whose viral loads are between 50 copies/ml and 200 copies/ml will continue the treatment regimen and latent cell sampling, but their regimens may be intensified as determined by the study team. Patients whose viral loads are 200 copies/ml or greater after Week 24 may continue their study regimens, but will no longer contribute latent cell samples.
This study will last 96 weeks. During the first 4 months of the study, patients will have 7 study visits; after that, study visits will be every 8 weeks until the end of the study. Medical history, clinical assessments, and blood collection will occur at every study visit. Pill and ENF vial counts will be assessed, and patients will be asked to complete a medication adherence questionnaire at selected study visits.
- Conditions
- HIV Infections
- Being tested
- Emtricitabine, Enfuvirtide, Ritonavir, Saquinavir, Tenofovir disoproxil fumarate
- Keywords
- Treatment Naive, HIV-1, Virus Replication, CD4-Positive T-Lymphocytes, Immunologic Memory, Pentafuside, Anti-HIV Agents, Drug Therapy, Combination, Saquinavir, Ritonavir, Tenofovir Disoproxil Fumarate, RNA, Viral, Viral Load, Fusion Inhibitors, Entry Inhibitors
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EmtricitabineDrug
Also called FTC, Emtriva
Will be administered as one 200-mg capsule orally daily
EnfuvirtideDrug
Also called ENF, Fuzeon, T-20
Will be administered as a 90-mg (1.0 mL) subcutaneous injection twice daily
RitonavirDrug
Also called RTV, Norvir
Will be administered as one 100-mg capsule orally twice daily
SaquinavirDrug
Also called Invirase, Saquinavir mesylate
Will be administered as five hard gel capsules orally twice daily
Tenofovir disoproxil fumarateDrug
Also called TDF, Viread
Will be administered as one 300-mg tablet orally daily
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Not described Receives: Drug: Emtricitabine; Drug: Enfuvirtide; Drug: Ritonavir; Drug: Saquinavir; Drug: Tenofovir disoproxil fumarate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frequency of latently infected CD4+ T cells from peripheral blood with replication-competent HIV-1 (in infectious units per million cells)
Measured: Throughout study
Secondary outcomes (12)
Any Grade 3 or 4 adverse experience, including Grade 3 or 4 laboratory value, sign or symptom, and all deaths.
Measured: Throughout study
Targeted events and toxicities will also be considered and these include injection site reactions (any grade), bacterial pneumonia, cellulitis
Measured: Throughout study
- Level of HIV-1 RNA in plasma as measured by the Roche Ultrasensitive assay
Measured: Throughout study
- Level of HIV-1 DNA in PBMC
Measured: Throughout study
- Frequency of 2-LTR in PBMC
Measured: Throughout study
-Sequence of HIV env and HIV pol genes
Measured: Throughout study
-CD8/CD38 antibody binding capacity (ABC)
Measured: Throughout study
- Level of HIV-1 RNA in cerebrospinal fluid
Measured: Throughout study
- Level of HIV-1 RNA in genital fluid
Measured: Throughout study
- Level of HIV-1 RNA in plasma as measured by an ultra-ultrasensitive assay
Measured: Throughout study
- Measures of cell surface density of chemokine (CCR5, CXCR5) receptors
Measured: Throughout study
- Responses to subject preferences and injection administration concerns questionnaires
Measured: Throughout study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jan 2003 (estimated)
- Study startOct 2003
- Primary completionDec 2007
- Study completionMay 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
- Responsible party
- Sponsor
- Investigators
- Joseph J. Eron, Jr., MD, Study chair, University of North Carolina, Chapel Hill
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00051831
- Sponsor's protocol ID
- A5173
- Other IDs
- 10006, ACTG A5173
- Status last verified
- Oct 2021
- First submitted
- 16 Jan 2003
- Last updated
- 1 Nov 2021
- Results posted
- No
Publications
Blankson JN, Persaud D, Siliciano RF. The challenge of viral reservoirs in HIV-1 infection. Annu Rev Med. 2002;53:557-93. doi: 10.1146/annurev.med.53.082901.104024.
PubMed 11818490Perelson AS, Essunger P, Cao Y, Vesanen M, Hurley A, Saksela K, Markowitz M, Ho DD. Decay characteristics of HIV-1-infected compartments during combination therapy. Nature. 1997 May 8;387(6629):188-91. doi: 10.1038/387188a0.
PubMed 9144290Pierson T, McArthur J, Siliciano RF. Reservoirs for HIV-1: mechanisms for viral persistence in the presence of antiviral immune responses and antiretroviral therapy. Annu Rev Immunol. 2000;18:665-708. doi: 10.1146/annurev.immunol.18.1.665.
PubMed 10837072Kilby JM, Hopkins S, Venetta TM, DiMassimo B, Cloud GA, Lee JY, Alldredge L, Hunter E, Lambert D, Bolognesi D, Matthews T, Johnson MR, Nowak MA, Shaw GM, Saag MS. Potent suppression of HIV-1 replication in humans by T-20, a peptide inhibitor of gp41-mediated virus entry. Nat Med. 1998 Nov;4(11):1302-7. doi: 10.1038/3293.
PubMed 9809555Gandhi RT, Bosch RJ, Aga E, Albrecht M, Demeter LM, Dykes C, Bastow B, Para M, Lai J, Siliciano RF, Siliciano JD, Eron JJ; AIDS Clinical Trials Group A5173 Team. No evidence for decay of the latent reservoir in HIV-1-infected patients receiving intensive enfuvirtide-containing antiretroviral therapy. J Infect Dis. 2010 Jan 15;201(2):293-6. doi: 10.1086/649569.
PubMed 20001856
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study to Measure the Clearance of Replication-Competent HIV-1 in Resting Memory CD4+ Cells in HIV-1-Infected Subjects Who Receive Enfuvirtide Plus Oral Combination Antiretroviral Therapy
- ClinicalTrials.gov ID
- NCT00051831
- Acronym / sponsor ID
- A5173
- Conditions
- HIV Infections
- Keywords
- Treatment Naive, HIV-1, Virus Replication, CD4-Positive T-Lymphocytes, Immunologic Memory, Pentafuside, Anti-HIV Agents, Drug Therapy, Combination
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
- Study start
- Oct 2003
- Primary completion
- Dec 2007 (actual)
- Study completion
- May 2008 (actual)
- First posted
- 20 Jan 2003 (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.
HIV replication in resting CD4 cells is so minimal that anti-HIV drugs often fail to destroy the virus in these cells. Enfuvirtide, also known as T-20, is a type of anti-HIV drug called a fusion inhibitor. The purpose of this study is to test the ability of a T-20-enhanced treatment regimen to decrease the number of resting CD4 cells that become infected with HIV.
Detailed description
While current HIV treatment with combination antiretroviral therapy (ART) has reduced morbidity and mortality, it does not eradicate or cure HIV infection. A possible explanation for this failure is the persistence of virus in long-lived reservoirs. Resting memory CD4 cells have been proposed as providing a cellular reservoir. Most patients who initiate ART during chronic HIV-1 infection do not experience a detectable reduction in HIV in the latent reservoir; this may be due to low levels of ongoing viral replication that maintains the resting CD4 cell reservoir. Increasing the potency of therapy by inhibiting new viral targets may result in a decrease in the number of latently infected cells and clearance of the latent reservoir. Addition of the fusion inhibitor T-20 to ART including reverse transcriptase inhibitors and protease inhibitors (PIs) may help achieve this goal. This study will evaluate whether treatment naive, chronically infected HIV patients treated with T-20 plus emtricitabine (FTC), ritonavir (RTV), saquinavir (SQV), and tenofovir disoproxil fumarate (TDF) have a measurable decline in the latently infected CD4 cell reservoir. Patients and their physicians may choose different PIs than RTV and SQV, but they will not be provided by the study.
Patients in this study will receive injections of T-20 twice daily in addition to oral FTC and TDF once daily and oral RTV and SQV twice daily. At Week 24, patients will have their latent cell reservoir sampled. Patients whose HIV viral loads are less than 50 copies/ml at or after Week 24 but prior to Week 48 will continue the treatment regimen through the end of the study; their latent cell reservoirs will be tested at Weeks 48, 72, and 96. Patients whose viral loads are between 50 copies/ml and 200 copies/ml will continue the treatment regimen and latent cell sampling, but their regimens may be intensified as determined by the study team. Patients whose viral loads are 200 copies/ml or greater after Week 24 may continue their study regimens, but will no longer contribute latent cell samples.
This study will last 96 weeks. During the first 4 months of the study, patients will have 7 study visits; after that, study visits will be every 8 weeks until the end of the study. Medical history, clinical assessments, and blood collection will occur at every study visit. Pill and ENF vial counts will be assessed, and patients will be asked to complete a medication adherence questionnaire at selected study visits.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Emtricitabine, Drug: Enfuvirtide, Drug: Ritonavir, Drug: Saquinavir, Drug: Tenofovir disoproxil fumarate |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- HIV-1 infected
- Viral load of 1,000 copies/ml or greater within 60 days prior to study entry
- CD4 count of 100 cells/mm3 or greater within 60 days prior to study entry
- Willing to use acceptable methods of contraception
Key exclusion criteria (11 listed)
- Previous treatment with any nucleoside analogue, nonnucleoside reverse transcriptase inhibitor, or fusion inhibitor for longer than 7 days
- Any previous treatment with T-20, lamivudine, or FTC
- HIV-related vaccine within 6 months prior to study entry
- Evidence of HIV seroconversion within 6 months prior to study entry
- Acute AIDS-defining opportunistic infection (OI). Patients who are not clinically stable or who have not been on therapy for the OI for at least 30 days prior to study entry are excluded. Patients who have no evidence of active disease and have been receiving maintenance therapy for AIDS-related OI for at least 30 days are not excluded.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EmtricitabineAlso: FTC, EmtrivaWill be administered as one 200-mg capsule orally daily | Drug | 1 |
| EnfuvirtideAlso: ENF, Fuzeon, T-20Will be administered as a 90-mg (1.0 mL) subcutaneous injection twice daily | Drug | 1 |
| RitonavirAlso: RTV, NorvirWill be administered as one 100-mg capsule orally twice daily | Drug | 1 |
| SaquinavirAlso: Invirase, Saquinavir mesylateWill be administered as five hard gel capsules orally twice daily | Drug | 1 |
| Tenofovir disoproxil fumarateAlso: TDF, VireadWill be administered as one 300-mg tablet orally daily | Drug | 1 |
Primary outcome
Frequency of latently infected CD4+ T cells from peripheral blood with replication-competent HIV-1 (in infectious units per million cells)
Time frame: Throughout study
12 secondary outcomes
Any Grade 3 or 4 adverse experience, including Grade 3 or 4 laboratory value, sign or symptom, and all deaths.
Time frame: Throughout study
Targeted events and toxicities will also be considered and these include injection site reactions (any grade), bacterial pneumonia, cellulitis
Time frame: Throughout study
- Level of HIV-1 RNA in plasma as measured by the Roche Ultrasensitive assay
Time frame: Throughout study
- Level of HIV-1 DNA in PBMC
Time frame: Throughout study
- Frequency of 2-LTR in PBMC
Time frame: Throughout study
-Sequence of HIV env and HIV pol genes
Time frame: Throughout study
-CD8/CD38 antibody binding capacity (ABC)
Time frame: Throughout study
- Level of HIV-1 RNA in cerebrospinal fluid
Time frame: Throughout study
- Level of HIV-1 RNA in genital fluid
Time frame: Throughout study
- Level of HIV-1 RNA in plasma as measured by an ultra-ultrasensitive assay
Time frame: Throughout study
- Measures of cell surface density of chemokine (CCR5, CXCR5) receptors
Time frame: Throughout study
- Responses to subject preferences and injection administration concerns questionnaires
Time frame: Throughout study
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 1 Nov 2021.
- Background: PubMed 11818490Blankson JN, Persaud D, Siliciano RF. The challenge of viral reservoirs in HIV-1 infection. Annu Rev Med. 2002;53:557-93. doi: 10.1146/annurev.med.53.082901.104024.
- Background: PubMed 9144290Perelson AS, Essunger P, Cao Y, Vesanen M, Hurley A, Saksela K, Markowitz M, Ho DD. Decay characteristics of HIV-1-infected compartments during combination therapy. Nature. 1997 May 8;387(6629):188-91. doi: 10.1038/387188a0.
- Background: PubMed 10837072Pierson T, McArthur J, Siliciano RF. Reservoirs for HIV-1: mechanisms for viral persistence in the presence of antiviral immune responses and antiretroviral therapy. Annu Rev Immunol. 2000;18:665-708. doi: 10.1146/annurev.immunol.18.1.665.
- Background: PubMed 9809555Kilby JM, Hopkins S, Venetta TM, DiMassimo B, Cloud GA, Lee JY, Alldredge L, Hunter E, Lambert D, Bolognesi D, Matthews T, Johnson MR, Nowak MA, Shaw GM, Saag MS. Potent suppression of HIV-1 replication in humans by T-20, a peptide inhibitor of gp41-mediated virus entry. Nat Med. 1998 Nov;4(11):1302-7. doi: 10.1038/3293.
- Derived from this study: PubMed 20001856Gandhi RT, Bosch RJ, Aga E, Albrecht M, Demeter LM, Dykes C, Bastow B, Para M, Lai J, Siliciano RF, Siliciano JD, Eron JJ; AIDS Clinical Trials Group A5173 Team. No evidence for decay of the latent reservoir in HIV-1-infected patients receiving intensive enfuvirtide-containing antiretroviral therapy. J Infect Dis. 2010 Jan 15;201(2):293-6. doi: 10.1086/649569.
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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.
Joseph J. Eron, Jr., MD study chair
University of North Carolina, Chapel Hill
7 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Emtricitabine, Enfuvirtide and Ritonavir in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 7 sites in 2 countries.
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 4 inclusion and 11 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 1 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States, Puerto Rico. 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.
What does the primary outcome measure?
Frequency of latently infected CD4+ T cells from peripheral blood with replication-competent HIV-1 (in infectious units per million cells) (time frame: Throughout study). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00051831, which also lists 5 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 1 Nov 2021.