HIV InfectionNCT00618371
Pilot Study of Adding Raltegravir (MK-0518) to Antiretroviral Therapy in Patients With Low Level Viremia
A study testing Raltegravir (MK-0518) in people with HIV Infection, run by University of Pittsburgh at 1 site in United States.
Trial summary
The medicines used to treat HIV can suppress but cannot kill all the virus in the body. A small amount of virus remains at low levels in the part of the blood called the plasma. It is of crucial importance to identify the source of the residual virus in patients receiving antiretroviral therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infection
- What is being tested?
- Raltegravir (MK-0518)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2007to Mar 2009
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 infection documented by positive HIV-1 ELISA and positive
- Male or female at least 18 years of age, and able to provide written, informed consent
- Current antiretroviral therapy with Department of Health and Human Services (DHHS)-recommended regimen: NRTIs + PI, NRTIs + NNRTI + PI, or NRTIs + NNRTI
- Screening CD4 > 200 cells/ µl and CD4%> 14%; does not require prophylaxis for opportunistic infections
- Receiving a stable antiretroviral regimen for 4 months prior to screening
- HIV-1 RNA level below the limit of detection by commercial HIV-1 RNA determination assays for at least 12 months prior to screening.
Show all 11Show fewer
- HIV RNA ≥ 0.6 copy RNA/ml plasma by SCA(single copy assay)
- Hgb ≥ 9.0 mg/dl, absolute neutrophil count > 1000/mm3, platelet count > 100,000/mm3
- Alkaline phosphatase, Aspartate transaminase (AST) and Alanine aminotransferase (ALT) < 2.0 x upper limit of normal
- Willing to take MK-0518 for 28 days in addition to ongoing antiretroviral therapy
- Be considered clinically stable, in the opinion of the investigator, at the time of entry into the study; i.e., clinical status and all chronic medications should be unchanged for at least two weeks prior to entry.
Who cannot join
- Prior participation in an MK-0518 or other integrase inhibitor trial
- Requires prohibited medications noted in the protocol
- Requires cytotoxic agents including hydroxyurea or vaccinations during the study period
- Received immunosuppressive therapy including steroids within one month prior to treatment in this study
- Used any investigational agents within a month prior to treatment in this study
- Documented resistance to any drug in each of the 4 classes of licensed antiretroviral agents by genotype or phenotype
Show all 12Show fewer
- Any febrile illness (T>38oC) in the 3 weeks prior to enrollment
- Any vaccination in the 6 weeks prior to enrollment
- Diagnosis of acute hepatitis due to any cause
- Positive Hepatitis B surface antigen
- Severe renal insufficiency defined as a calculated creatinine clearance at time of screening as < 30 ml/min, based on the Cockcroft-Gault equation.
- Condition (including but not limited to alcohol or other substance use) which in the opinion of the investigator would interfere with patient compliance or safety
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213
About this study
Official title: Investigating the Source of HIV-1 Viremia in Patients on Antiretroviral Therapy Through Intensification With MK-0518
The medicines used to treat HIV can suppress but cannot kill all the virus in the body. A small amount of virus remains at low levels in the part of the blood called the plasma. It is of crucial importance to identify the source of the residual virus in patients receiving antiretroviral therapy. The purpose of this study is to investigate whether the source of low level plasma virus is from latent (old) infection or ongoing (new) infection. MK-0518 is a investigational drug, which means that is not yet FDA approved, that works in a different way to other anti-HIV medicines to help kill the virus. We hypothesize that addition of MK-0518 to a stable anti-HIV regimen will reduce the viral load further in patients with undetectable plasma virus.
Read the detailed description
This is a non-randomized, non-comparative, single center trial of antiretroviral therapy intensification using the investigational integrase inhibitor MK-0518 and an investigational viral load assay to measure response to additional antiviral therapy. Eighteen patients will receive open-label MK-0518 400 mg P.O. every 12 hours for 28 days in addition to their prescribed antiretroviral therapy. Patients will take their doses of MK-0518 without regard to food. The study will enroll patients on antiretroviral therapy regimens with Cluster of Differentiation 4 (CD4) counts greater than 200 cells/ul, HIV-1 RNA levels <50 copies RNA/ml plasma using a commercial assay(conventional Amplicor) and with detectable plasma virus (viral loads ≥ 1 copies RNA/ml plasma, Single copy assay, "SCA"). Acceptable antiretroviral regimens will include those on Nucleoside reverse transcriptase inhibitors ("NRTIs") + protease inhibitor (PI)I, NRTIs + non-nucleoside reverse transcriptase inhibitors (NNRTIs), + PI, or NRTIs + NNRTI-containing regimens. Patients cannot have prior evidence of resistance to antiretroviral drugs. Patients will be screened for intensification by history, physical exam, and laboratory evaluations (see below). Patients who are eligible and who agree to participate will intensify their antiretroviral therapy for 28 days with MK-0518 400 mg by mouth twice a day. During the 28- day drug addition, patients will have samples drawn for SCA assay at entry and on days 7, 14, 21, and 28 (+/- 1 d), with the last day of intensification as day 28. Patients will have additional phlebotomy after intensification on days 29, 30, 35, 42, 49 and 58 (+/- 1 day). The intensification period is followed by a post- intensification period to determine whether removal of the drug resulted in viral RNA changes.
- Conditions
- HIV Infection
- Being tested
- Raltegravir (MK-0518)
- Keywords
- Intensification, HIV viremia, Human Immunodeficiency Virus
- Medical subject headings
- HIV Infections, Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Raltegravir (MK-0518)Drug
Also called MK-0518
Antiretroviral drug intensification with Raltegravir (MK0518) 400mg orally every 12 hours for 28 days in addition to the prescribed antiretroviral therapy
| Study group | Role | What they receive |
|---|---|---|
| Raltegravir intensification | Experimental | Patients will be administered raltegravir 400 mg orally twice daily in addition to antiretroviral therapy Receives: Drug: Raltegravir (MK-0518) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With HIV-1 RNA Response: ≥ 1 Log Decrease in Viral Load
HIV RNA levels were determined with a non-commercial, sensitive single copy assay for HIV. The primary outcome measure was to determine the number of individuals with ≥10fold decrease in HIV RNA
Measured: 4 weeks
Secondary outcomes (1)
Proviral DNA Response, HIV-1 Sequence Variation Levels of Cell Associated HIV DNA and Genetic Variation in HIV During Raltegravir Addition in Individuals Who Have Declines in HIV
We planned to compare HIV DNA levels and HIV genetic variation in individuals with and without ≥10 fold decreases in HIV RNA. As none of the patients had a decline in viral RNA, this analysis could not be readily analyzed
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2008 (estimated)
- Study startOct 2007
- Primary completionMar 2009
- Study completionMar 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionStudies of the same condition, open and under way.
- More trials run by University of PittsburghThe 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
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pittsburgh
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Frank Maldarelli, National Cancer Institute (NCI)
- Investigators
- Deborah McMahon, MD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00618371
- Sponsor's protocol ID
- 27XS050
- Other IDs
- HHSN261200800001E, ZIABC011464
- Status last verified
- Dec 2016
- First submitted
- 29 Sep 2007
- Last updated
- 1 Feb 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No: Data were analyzed and there is no plan to make individual participant data available
Publications
Natarajan V, Bosche M, Metcalf JA, Ward DJ, Lane HC, Kovacs JA. HIV-1 replication in patients with undetectable plasma virus receiving HAART. Highly active antiretroviral therapy. Lancet. 1999 Jan 9;353(9147):119-20. doi: 10.1016/s0140-6736(05)76156-0. No abstract available.
PubMed 10023903Dornadula G, Zhang H, VanUitert B, Stern J, Livornese L Jr, Ingerman MJ, Witek J, Kedanis RJ, Natkin J, DeSimone J, Pomerantz RJ. Residual HIV-1 RNA in blood plasma of patients taking suppressive highly active antiretroviral therapy. JAMA. 1999 Nov 3;282(17):1627-32. doi: 10.1001/jama.282.17.1627.
PubMed 10553788Zhang L, Ramratnam B, Tenner-Racz K, He Y, Vesanen M, Lewin S, Talal A, Racz P, Perelson AS, Korber BT, Markowitz M, Ho DD. Quantifying residual HIV-1 replication in patients receiving combination antiretroviral therapy. N Engl J Med. 1999 May 27;340(21):1605-13. doi: 10.1056/NEJM199905273402101.
PubMed 10341272Palmer S, Wiegand AP, Maldarelli F, Bazmi H, Mican JM, Polis M, Dewar RL, Planta A, Liu S, Metcalf JA, Mellors JW, Coffin JM. New real-time reverse transcriptase-initiated PCR assay with single-copy sensitivity for human immunodeficiency virus type 1 RNA in plasma. J Clin Microbiol. 2003 Oct;41(10):4531-6. doi: 10.1128/JCM.41.10.4531-4536.2003.
PubMed 14532178Maldarelli F, Palmer S, King MS, Wiegand A, Polis MA, Mican J, Kovacs JA, Davey RT, Rock-Kress D, Dewar R, Liu S, Metcalf JA, Rehm C, Brun SC, Hanna GJ, Kempf DJ, Coffin JM, Mellors JW. ART suppresses plasma HIV-1 RNA to a stable set point predicted by pretherapy viremia. PLoS Pathog. 2007 Apr;3(4):e46. doi: 10.1371/journal.ppat.0030046.
PubMed 17411338Hazuda DJ, Wolfe AL, Hastings JC, Robbins HL, Graham PL, LaFemina RL, Emini EA. Viral long terminal repeat substrate binding characteristics of the human immunodeficiency virus type 1 integrase. J Biol Chem. 1994 Feb 11;269(6):3999-4004.
PubMed 8307956McMahon D, Jones J, Wiegand A, Gange SJ, Kearney M, Palmer S, McNulty S, Metcalf JA, Acosta E, Rehm C, Coffin JM, Mellors JW, Maldarelli F. Short-course raltegravir intensification does not reduce persistent low-level viremia in patients with HIV-1 suppression during receipt of combination antiretroviral therapy. Clin Infect Dis. 2010 Mar 15;50(6):912-9. doi: 10.1086/650749.
PubMed 20156060
Study at a glance
From the registry record, last updated by the sponsor on 1 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigating the Source of HIV-1 Viremia in Patients on Antiretroviral Therapy Through Intensification With MK-0518
- ClinicalTrials.gov ID
- NCT00618371
- Acronym / sponsor ID
- 27XS050
- Conditions
- HIV Infection
- Keywords
- Intensification, HIV viremia, Human Immunodeficiency Virus
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- University of PittsburghUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Oct 2007
- Primary completion
- Mar 2009 (actual)
- Study completion
- Mar 2009 (actual)
- First posted
- 20 Feb 2008 (estimated)
- Results
- Posted 6 Dec 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The medicines used to treat HIV can suppress but cannot kill all the virus in the body. A small amount of virus remains at low levels in the part of the blood called the plasma. It is of crucial importance to identify the source of the residual virus in patients receiving antiretroviral therapy. The purpose of this study is to investigate whether the source of low level plasma virus is from latent (old) infection or ongoing (new) infection. MK-0518 is a investigational drug, which means that is not yet FDA approved, that works in a different way to other anti-HIV medicines to help kill the virus. We hypothesize that addition of MK-0518 to a stable anti-HIV regimen will reduce the viral load further in patients with undetectable plasma virus.
Detailed description
This is a non-randomized, non-comparative, single center trial of antiretroviral therapy intensification using the investigational integrase inhibitor MK-0518 and an investigational viral load assay to measure response to additional antiviral therapy. Eighteen patients will receive open-label MK-0518 400 mg P.O. every 12 hours for 28 days in addition to their prescribed antiretroviral therapy. Patients will take their doses of MK-0518 without regard to food. The study will enroll patients on antiretroviral therapy regimens with Cluster of Differentiation 4 (CD4) counts greater than 200 cells/ul, HIV-1 RNA levels <50 copies RNA/ml plasma using a commercial assay(conventional Amplicor) and with detectable plasma virus (viral loads ≥ 1 copies RNA/ml plasma, Single copy assay, "SCA"). Acceptable antiretroviral regimens will include those on Nucleoside reverse transcriptase inhibitors ("NRTIs") + protease inhibitor (PI)I, NRTIs + non-nucleoside reverse transcriptase inhibitors (NNRTIs), + PI, or NRTIs + NNRTI-containing regimens. Patients cannot have prior evidence of resistance to antiretroviral drugs. Patients will be screened for intensification by history, physical exam, and laboratory evaluations (see below). Patients who are eligible and who agree to participate will intensify their antiretroviral therapy for 28 days with MK-0518 400 mg by mouth twice a day. During the 28- day drug addition, patients will have samples drawn for SCA assay at entry and on days 7, 14, 21, and 28 (+/- 1 d), with the last day of intensification as day 28. Patients will have additional phlebotomy after intensification on days 29, 30, 35, 42, 49 and 58 (+/- 1 day). The intensification period is followed by a post- intensification period to determine whether removal of the drug resulted in viral RNA changes.
Study design
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Raltegravir intensification | Experimental | Drug: Raltegravir (MK-0518)Patients will be administered raltegravir 400 mg orally twice daily in addition to antiretroviral therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- HIV-1 infection documented by positive HIV-1 ELISA and positive
- Male or female at least 18 years of age, and able to provide written, informed consent
- Current antiretroviral therapy with Department of Health and Human Services (DHHS)-recommended regimen: NRTIs + PI, NRTIs + NNRTI + PI, or NRTIs + NNRTI
- Screening CD4 > 200 cells/ µl and CD4%> 14%; does not require prophylaxis for opportunistic infections
- Receiving a stable antiretroviral regimen for 4 months prior to screening
Key exclusion criteria (12 listed)
- Prior participation in an MK-0518 or other integrase inhibitor trial
- Requires prohibited medications noted in the protocol
- Requires cytotoxic agents including hydroxyurea or vaccinations during the study period
- Received immunosuppressive therapy including steroids within one month prior to treatment in this study
- Used any investigational agents within a month prior to treatment in this study
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 |
|---|---|---|
| Raltegravir (MK-0518)Also: MK-0518Antiretroviral drug intensification with Raltegravir (MK0518) 400mg orally every 12 hours for 28 days in addition to the prescribed antiretroviral therapy | Drug | Raltegravir intensification |
Primary outcome
Number of Participants With HIV-1 RNA Response: ≥ 1 Log Decrease in Viral Load
Time frame: 4 weeks
HIV RNA levels were determined with a non-commercial, sensitive single copy assay for HIV. The primary outcome measure was to determine the number of individuals with ≥10fold decrease in HIV RNA
1 secondary outcome
Proviral DNA Response, HIV-1 Sequence Variation Levels of Cell Associated HIV DNA and Genetic Variation in HIV During Raltegravir Addition in Individuals Who Have Declines in HIV
Time frame: 4 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 10023903Natarajan V, Bosche M, Metcalf JA, Ward DJ, Lane HC, Kovacs JA. HIV-1 replication in patients with undetectable plasma virus receiving HAART. Highly active antiretroviral therapy. Lancet. 1999 Jan 9;353(9147):119-20. doi: 10.1016/s0140-6736(05)76156-0. No abstract available.
- Background: PubMed 10553788Dornadula G, Zhang H, VanUitert B, Stern J, Livornese L Jr, Ingerman MJ, Witek J, Kedanis RJ, Natkin J, DeSimone J, Pomerantz RJ. Residual HIV-1 RNA in blood plasma of patients taking suppressive highly active antiretroviral therapy. JAMA. 1999 Nov 3;282(17):1627-32. doi: 10.1001/jama.282.17.1627.
- Background: PubMed 10341272Zhang L, Ramratnam B, Tenner-Racz K, He Y, Vesanen M, Lewin S, Talal A, Racz P, Perelson AS, Korber BT, Markowitz M, Ho DD. Quantifying residual HIV-1 replication in patients receiving combination antiretroviral therapy. N Engl J Med. 1999 May 27;340(21):1605-13. doi: 10.1056/NEJM199905273402101.
- Background: PubMed 14532178Palmer S, Wiegand AP, Maldarelli F, Bazmi H, Mican JM, Polis M, Dewar RL, Planta A, Liu S, Metcalf JA, Mellors JW, Coffin JM. New real-time reverse transcriptase-initiated PCR assay with single-copy sensitivity for human immunodeficiency virus type 1 RNA in plasma. J Clin Microbiol. 2003 Oct;41(10):4531-6. doi: 10.1128/JCM.41.10.4531-4536.2003.
- Background: PubMed 17411338Maldarelli F, Palmer S, King MS, Wiegand A, Polis MA, Mican J, Kovacs JA, Davey RT, Rock-Kress D, Dewar R, Liu S, Metcalf JA, Rehm C, Brun SC, Hanna GJ, Kempf DJ, Coffin JM, Mellors JW. ART suppresses plasma HIV-1 RNA to a stable set point predicted by pretherapy viremia. PLoS Pathog. 2007 Apr;3(4):e46. doi: 10.1371/journal.ppat.0030046.
- Background: PubMed 8307956Hazuda DJ, Wolfe AL, Hastings JC, Robbins HL, Graham PL, LaFemina RL, Emini EA. Viral long terminal repeat substrate binding characteristics of the human immunodeficiency virus type 1 integrase. J Biol Chem. 1994 Feb 11;269(6):3999-4004.
- Derived from this study: PubMed 20156060McMahon D, Jones J, Wiegand A, Gange SJ, Kearney M, Palmer S, McNulty S, Metcalf JA, Acosta E, Rehm C, Coffin JM, Mellors JW, Maldarelli F. Short-course raltegravir intensification does not reduce persistent low-level viremia in patients with HIV-1 suppression during receipt of combination antiretroviral therapy. Clin Infect Dis. 2010 Mar 15;50(6):912-9. doi: 10.1086/650749.
- Individual participant dataSharing planned: No. Data were analyzed and there is no plan to make individual participant data available
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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.
Deborah McMahon, MD principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Raltegravir (MK-0518) in people with HIV Infection, run by University of Pittsburgh at 1 site in United States.
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 11 inclusion and 12 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 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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?
Yes. Results are posted in the registry (first posted 6 Dec 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With HIV-1 RNA Response: ≥ 1 Log Decrease in Viral Load (time frame: 4 weeks). 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 NCT00618371, which also lists 7 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 Feb 2017.