Immune Reconstitution Inflammatory SyndromeCADIRISNCT00988780
Maraviroc (CCR5) Antagonism to Decrease the Incidence of the Immune Reconstitution Inflammatory Syndrome in HIV-Infected Patients
A study testing maraviroc in people with Immune Reconstitution Inflammatory Syndrome and HIV, run by Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran at 10 sites in 3 countries.
Trial summary
The purpose of this study is to determine if Maraviroc administration can decrease IRIS incidence in HIV infected patients initiating ARV therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Immune Reconstitution Inflammatory Syndrome, HIV, HIV Infections
- What is being tested?
- maraviroc
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 276 participants
- Where
- 10 sitesin 3 countries
- Study dates
- Dec 2009to Apr 2013
- 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 infection, as documented by any licensed rapid test kit and confirmed by Western blot or ELISA test kit at any time prior to study enrollment.
- Plasma HIV-1 RNA is acceptable as an alternative confirmatory test.
- Men and women age > 18 years.
- Have not received any antiretroviral treatment before entering the study.
- Patients who received Single dose nevirapine or any duration of AZT for PMTC will not be considered ARV naïve.
- CD4+ cell count of </=100 cells/mm3 obtained within 90 days prior to study entry.
Show all 19Show fewer
- HIV RNA level > 1,000 copies/mL obtained within 90 days prior to study entry.
- Patients with an opportunistic or HIV-related infection may be included according to the clinical judgment of the main investigator in each center when the patient is ready and able to start ARV therapy.
- Laboratory values obtained within 30 days prior to study entry:
- Absolute neutrophil count (ANC) > 500/mm3.
- Hemoglobin > 8.0 g/dL.
- Platelet count > 50,000/mm3.
- AST (SGOT), ALT (SGPT), and alkaline phosphatase minor of 5 times ULN.
- Total bilirubin minor of 2.5 times ULN.
- Creatinine clearance minor of 50* mL/min as estimated by the Cockcroft-Gault equation or Creatinine Clearance > 50ml/min as calculated by a formal creatinine clearance measurement
- All women of reproductive potential (have not reached menopause or undergone hysterectomy, oophorectomy, or tubal ligation) must have a negative serum or urine b-HCG pregnancy test performed within 7 days before study entry.
- Female subjects who are not of reproductive potential (have reached menopause or undergone hysterectomy, oophorectomy, or tubal ligation) or whose male partner has undergone successful vasectomy with resultant azoospermia or has azoospermia for any other reason, are eligible without requiring the use of contraception. Documentation of menopause, sterilization (hysterectomy, oophorectomy, tubal ligation, or vasectomy) and azoospermia by patient-reported history is acceptable.
- All subjects must agree not to participate in a conception process (i.e., active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization), and if participating in sexual activity that could lead to pregnancy, the female study volunteer/male partner must agree to use a form of contraception as specified in the note below while receiving protocol-specified medication(s) and for one month after stopping the medication(s).
- Ability and willingness of subject or legal guardian/representative to give written informed consent.
Who cannot join
- Pregnancy and breast-feeding.
- Active neoplasia or previous history of neoplasia. (Except localized non visceral Kaposi´s Sarcoma; localized squamous or basal cell carcinoma of the skin, or intraepithelial cervical neoplasia grade III or less).
- Use of the following drugs within 180 days prior to study entry: systemic cancer chemotherapy, systemic investigational agents, and immunomodulators (growth factors, immune globulin, interleukins, interferons).
- Use of systemic corticosteroids in the last 2 weeks prior to randomization.
- Decompensated liver disease (defined as stage C of Child-Pugh classification) at the beginning of the study.
- An altered mental status that in the opinion of the investigator, will compromise the adherence to the protocol.
Show all 10Show fewer
- Allergy/sensitivity to study drug(s) or their formulations that cannot be substituted by another agent as described in section 5.1
- Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements.
- Serious illness that renders a subject unable to take the antiretroviral study regimen.
- Serious medical illness that in the opinion of the investigator compromises the adherence and/or follow up of the protocol.
Trial locations and contacts
10 sites in 3 countries.
10 sites in 3 countries
Mexico5 sites
Hospital Civil de Guadalajara
Guadalajara, Jalisco, 44280
Hospital General de León
León, Guanajuato, 37230
Hospital General de México
Mexico City, Mexico City, 06726
Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
Mexico City, Mexico City, 14000
Hospital Central Dr. Ignacio Morones Prieto
San Luis Potosí City, San Luis Potosí, 78240
United States4 sites
NIH/NIAD
Bethesda, Maryland, 20892
Center for AIDS Research. Case Western Reserve University
Cleveland, Ohio, 44106
Center for Clinical Epidemiology and Biostatistics. University of Pennsylvania School of Medicine
Philadelphia, Pennsylvania, 19104
HIV-1 Immunopathogenesis Laboratory. The Wistar Institute
Philadelphia, Pennsylvania, 19104
South Africa1 site
Clinical HIV Research Unit. Themba Lethu Clinic. Helen Joseph Hospital
Johannesburg, Gauteng, 2092
About this study
Official title: CCR5 Antagonism to Decrease the Incidence of the Immune Reconstitution Inflammatory Syndrome in HIV-Infected Patients
The purpose of this study is to determine if Maraviroc administration can decrease IRIS incidence in HIV infected patients initiating ARV therapy.
Read the detailed description
This is a randomized, double blind, placebo-controlled, multicenter study testing the utility of a CCR5 antagonist (Maraviroc) as an adjuvant to a standard HAART regimen to decrease the incidence of Immune Reconstitution Inflammatory Syndrome (IRIS) in HIV-infected patients naïve to antiretroviral treatment. The study duration will be 60 weeks, 276 subjects (138 per arm) will be recruited. The population included will be HIV-infected patients starting antiretroviral (ARV) therapy at the participating centers in Mexico and South Africa with a CD4 T cell count <100 cells/ul. Subjects will be randomized to receive either Maraviroc (study drug) or placebo in addition to background ARV therapy. The background antiretroviral regimen for all subjects will be: Efavirenz 600mg QD + Tenofovir 300 mg / Emtricitabine 200 mg QD; subjects will be randomized to one of the following arms: Arm A: background ARV + maraviroc 600mg po BID; Arm B: background ARV + placebo po BID. Patients will be followed for 48 weeks. The primary endpoint will be the occurrence of a defined IRIS event by week 24 of follow up. The success of the ARV therapy will also be evaluated by virologic and immunologic response at 24 and 48 weeks. Three immunology sub-studies are planned: 1) Sub-study A will be conformed by a subgroup of 40 subjects (20 from Mexico and 20 from South Africa), additional blood sampling will be performed to evaluate expression of immune activation markers; movement of central memory T cells into cell cycle and frequencies of expandable pathogen-reactive CD4+ and CD8+ T cells in circulation; 2) Sub-study B will be conformed by another subgroup of 60 subjects (all from South Africa), additional blood sampling will be performed to evaluate monocyte and CD4 T cell gene expression as related to activation-induced apoptosis and cytokine secretion.; 3) Sub-study C will evaluate the incidence of thromboembolic disease in the study patients along with baseline evaluation of possible bio-markers of pro-coagulant state.
- Being tested
- maraviroc, Placebo
- Keywords
- Immune reconstitution inflammatory syndrome, CCR5 antagonist, Maraviroc, HIV, treatment naive
- Medical subject headings
- Immune Reconstitution Inflammatory Syndrome, HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
maravirocDrug
Also called Selzentry, Stocrin, Truvada
Maraviroc 600mg po BID every day from the entry visit until week 48 or until IRIS event or unacceptable toxicity develops.
Efavirenz 600 mg qd every day from the entry visit until week 48 or until IRIS event or unacceptable toxicity develops.
Tenofovir/Emtricitabine 300/200 mg qd from the entry visit until week 48 or until IRIS event or unacceptable toxicity develops.
PlaceboDrug
Also called Stocrin, Truvada
Placebo tablets po BID every day from the entry visit until week 48 or until IRIS event or unacceptable toxicity develops.
Efavirenz 600 mg qd every day from the entry visit until week 48 or until IRIS event or unacceptable toxicity develops.
Tenofovir/Emtricitabine 300/200 mg qd from the entry visit until week 48 or until IRIS event or unacceptable toxicity develops.
| Study group | Role | What they receive |
|---|---|---|
| Maraviroc | Experimental | Maraviroc 600mg po BID
Background antiretroviral regimen (Efavirenz 600mg QD + Tenofovir 300 mg /Emtricitabine 200 mg QD) plus Maraviroc 600 mg BID Receives: Drug: maraviroc |
| Placebo | Placebo comparator | Placebo po BID
Background antiretroviral regimen (Efavirenz 600mg QD + Tenofovir 300 mg /Emtricitabine 200 mg QD plus Placebo po BID Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to occurrence of an IRIS event
Measured: The initial 24 week period of observation
Secondary outcomes (19)
Time to occurrence of a severe IRIS event
Measured: The initial 24 week period of observation
Occurrence of either an IRIS event or death
Measured: By 24 and 48 weeks
Proportion of subjects who develops an IRIS case
Measured: By week 24
Proportion of subjects who develop a severe IRIS case
Measured: Week 24
Proportion of subjects who develop a confirmed, non dermatologic IRIS case
Measured: Week 24
Proportion of subjects who develop an unmasking or paradoxical IRIS event
Measured: Week 24
Frequency of cardiovascular, cerebrovascular, non AIDS related neoplasia, cirrhosis, renal failure and death in both treatment arms
Measured: During the study (from entry to week 60)
Frequency of AIDS defining events and AIDS related events in both arms of treatment
Measured: From basline to study end
General survival
Measured: At week 24 and 48
Survival without IRIS
Measured: At weeks 24 and 48
Proportion of patients with VL<50 copies/mL
Measured: At weeks 8, 24 and 48
Changes form baseline in CD4+ cells count
Measured: From baseline to weeks 12, 24 and 48
Safety and tolerability of the treatment regimens
Measured: Along the study
Incidence of HIV drug resistance
Measured: Baseline to week 60
Prevalence of CCR5 tropism
Measured: Baseline
Prevalence of CCR5 HIV tropism
Measured: At virological failure occurrence
Baseline predictors of IRIS
Measured: Baseline
Genetic polymorphisms associated with the occurrence of IRIS
Measured: Baseline
To evaluate the rol of biomarkers (CRP) in predicting or identifying IRIS and the effect of Maraviroc on this marker
Measured: Baseline to IRIS event
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2009 (estimated)
- Study startDec 2009
- Primary completionMar 2013 (estimated)
- Study completionApr 2013 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (45)Papers the sponsor has linked to this study.
- Other trials for Immune Reconstitution Inflammatory SyndromeStudies of the same condition, open and under way.
- 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 276 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
- Sponsor type
- University, hospital or other
- Collaborators
- University of Witwatersrand, South Africa, Case Western Reserve University, The Wistar Institute, University of Pennsylvania
- Responsible party
- Principal investigator, Juan G. Sierra Madero, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
- Investigators
- Ian Sanne, MBBCH, FCP, Principal investigator, University of the Witwatersrand. Themba Lethu Clinic.Michael M. Lederman, MD, Principal investigator, Center for AIDS Research. Case Western Reserve UniversityLuis J Montaner, M.Sc., Principal investigator, HIV-1 Immunopathogenesis Laboratory. The Wistar InstituteLivio Azzoni, MD, PhD, Principal investigator, HIV-1 Immunopathogenesis Laboratory. The Wistar InstituteJuan G Sierra Madero, MD, Principal investigator, Insituto Nacional de Nutricion de Ciencias Medicas y Nutricion Salvador ZubiranSusan Ellenberg, Ph.D., Principal investigator, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of MedicineIrini Sereti, M.D., MHS, Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00988780
- Sponsor's protocol ID
- The CADIRIS Study
- Acronym
- CADIRIS
- Status last verified
- Nov 2012
- First submitted
- 1 Oct 2009
- Last updated
- 27 Nov 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Jensen-Fangel S, Pedersen L, Pedersen C, Larsen CS, Tauris P, Moller A, Sorensen HT, Obel N. Low mortality in HIV-infected patients starting highly active antiretroviral therapy: a comparison with the general population. AIDS. 2004 Jan 2;18(1):89-97. doi: 10.1097/00002030-200401020-00011.
PubMed 15090834Corey DM, Kim HW, Salazar R, Illescas R, Villena J, Gutierrez L, Sanchez J, Tabet SR. Brief report: effectiveness of combination antiretroviral therapy on survival and opportunistic infections in a developing world setting: an observational cohort study. J Acquir Immune Defic Syndr. 2007 Apr 1;44(4):451-5. doi: 10.1097/QAI.0b013e31802f8512.
PubMed 17195766Lederman MM. Immune restoration and CD4+ T-cell function with antiretroviral therapies. AIDS. 2001 Feb;15 Suppl 2:S11-5. doi: 10.1097/00002030-200102002-00003.
PubMed 11424971Lawn SD, Myer L, Bekker LG, Wood R. CD4 cell count recovery among HIV-infected patients with very advanced immunodeficiency commencing antiretroviral treatment in sub-Saharan Africa. BMC Infect Dis. 2006 Mar 21;6:59. doi: 10.1186/1471-2334-6-59.
PubMed 16551345Battegay M, Nuesch R, Hirschel B, Kaufmann GR. Immunological recovery and antiretroviral therapy in HIV-1 infection. Lancet Infect Dis. 2006 May;6(5):280-7. doi: 10.1016/S1473-3099(06)70463-7.
PubMed 16631548Murdoch DM, Venter WD, Van Rie A, Feldman C. Immune reconstitution inflammatory syndrome (IRIS): review of common infectious manifestations and treatment options. AIDS Res Ther. 2007 May 8;4:9. doi: 10.1186/1742-6405-4-9.
PubMed 17488505Autran B, Carcelain G, Li TS, Blanc C, Mathez D, Tubiana R, Katlama C, Debre P, Leibowitch J. Positive effects of combined antiretroviral therapy on CD4+ T cell homeostasis and function in advanced HIV disease. Science. 1997 Jul 4;277(5322):112-6. doi: 10.1126/science.277.5322.112.
PubMed 9204894Shelburne SA, Visnegarwala F, Darcourt J, Graviss EA, Giordano TP, White AC Jr, Hamill RJ. Incidence and risk factors for immune reconstitution inflammatory syndrome during highly active antiretroviral therapy. AIDS. 2005 Mar 4;19(4):399-406. doi: 10.1097/01.aids.0000161769.06158.8a.
PubMed 15750393Lederman MM, Penn-Nicholson A, Cho M, Mosier D. Biology of CCR5 and its role in HIV infection and treatment. JAMA. 2006 Aug 16;296(7):815-26. doi: 10.1001/jama.296.7.815.
PubMed 16905787Westby M, van der Ryst E. CCR5 antagonists: host-targeted antivirals for the treatment of HIV infection. Antivir Chem Chemother. 2005;16(6):339-54. doi: 10.1177/095632020501600601.
PubMed 16329283Knobel H, Alonso J, Casado JL, Collazos J, Gonzalez J, Ruiz I, Kindelan JM, Carmona A, Juega J, Ocampo A; GEEMA Study Group. Validation of a simplified medication adherence questionnaire in a large cohort of HIV-infected patients: the GEEMA Study. AIDS. 2002 Mar 8;16(4):605-13. doi: 10.1097/00002030-200203080-00012.
PubMed 11873004French MA, Lenzo N, John M, Mallal SA, McKinnon EJ, James IR, Price P, Flexman JP, Tay-Kearney ML. Immune restoration disease after the treatment of immunodeficient HIV-infected patients with highly active antiretroviral therapy. HIV Med. 2000 Mar;1(2):107-15. doi: 10.1046/j.1468-1293.2000.00012.x.
PubMed 11737333Jevtovic DJ, Salemovic D, Ranin J, Pesic I, Zerjav S, Djurkovic-Djakovic O. The prevalence and risk of immune restoration disease in HIV-infected patients treated with highly active antiretroviral therapy. HIV Med. 2005 Mar;6(2):140-3. doi: 10.1111/j.1468-1293.2005.00277.x.
PubMed 15807721French MA, Price P, Stone SF. Immune restoration disease after antiretroviral therapy. AIDS. 2004 Aug 20;18(12):1615-27. doi: 10.1097/01.aids.0000131375.21070.06.
PubMed 15280772Singh N, Perfect JR. Immune reconstitution syndrome associated with opportunistic mycoses. Lancet Infect Dis. 2007 Jun;7(6):395-401. doi: 10.1016/S1473-3099(07)70085-3.
PubMed 17521592
Study at a glance
From the registry record, last updated by the sponsor on 27 Nov 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CCR5 Antagonism to Decrease the Incidence of the Immune Reconstitution Inflammatory Syndrome in HIV-Infected Patients
- ClinicalTrials.gov ID
- NCT00988780
- Acronym / sponsor ID
- CADIRIS / The CADIRIS Study
- Keywords
- Immune reconstitution inflammatory syndrome, CCR5 antagonist, Maraviroc, HIV, treatment naive
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 276 participants (estimated)
- Lead sponsor
- Instituto Nacional de Ciencias Medicas y Nutricion Salvador ZubiranUniversity, hospital or other
- Collaborators
- University of Witwatersrand, South Africa, Case Western Reserve University, The Wistar Institute, University of Pennsylvania
- Study start
- Dec 2009
- Primary completion
- Mar 2013 (estimated)
- Study completion
- Apr 2013 (estimated)
- First posted
- 2 Oct 2009 (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.
The purpose of this study is to determine if Maraviroc administration can decrease IRIS incidence in HIV infected patients initiating ARV therapy.
Detailed description
This is a randomized, double blind, placebo-controlled, multicenter study testing the utility of a CCR5 antagonist (Maraviroc) as an adjuvant to a standard HAART regimen to decrease the incidence of Immune Reconstitution Inflammatory Syndrome (IRIS) in HIV-infected patients naïve to antiretroviral treatment. The study duration will be 60 weeks, 276 subjects (138 per arm) will be recruited. The population included will be HIV-infected patients starting antiretroviral (ARV) therapy at the participating centers in Mexico and South Africa with a CD4 T cell count <100 cells/ul. Subjects will be randomized to receive either Maraviroc (study drug) or placebo in addition to background ARV therapy. The background antiretroviral regimen for all subjects will be: Efavirenz 600mg QD + Tenofovir 300 mg / Emtricitabine 200 mg QD; subjects will be randomized to one of the following arms: Arm A: background ARV + maraviroc 600mg po BID; Arm B: background ARV + placebo po BID. Patients will be followed for 48 weeks. The primary endpoint will be the occurrence of a defined IRIS event by week 24 of follow up. The success of the ARV therapy will also be evaluated by virologic and immunologic response at 24 and 48 weeks. Three immunology sub-studies are planned: 1) Sub-study A will be conformed by a subgroup of 40 subjects (20 from Mexico and 20 from South Africa), additional blood sampling will be performed to evaluate expression of immune activation markers; movement of central memory T cells into cell cycle and frequencies of expandable pathogen-reactive CD4+ and CD8+ T cells in circulation; 2) Sub-study B will be conformed by another subgroup of 60 subjects (all from South Africa), additional blood sampling will be performed to evaluate monocyte and CD4 T cell gene expression as related to activation-induced apoptosis and cytokine secretion.; 3) Sub-study C will evaluate the incidence of thromboembolic disease in the study patients along with baseline evaluation of possible bio-markers of pro-coagulant state.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Maraviroc | Experimental | Drug: maravirocMaraviroc 600mg po BID Background antiretroviral regimen (Efavirenz 600mg QD + Tenofovir 300 mg /Emtricitabine 200 mg QD) plus Maraviroc 600 mg BID |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo po BID Background antiretroviral regimen (Efavirenz 600mg QD + Tenofovir 300 mg /Emtricitabine 200 mg QD plus Placebo po BID |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- HIV-1 infection, as documented by any licensed rapid test kit and confirmed by Western blot or ELISA test kit at any time prior to study enrollment.
- Plasma HIV-1 RNA is acceptable as an alternative confirmatory test.
- Men and women age > 18 years.
- Have not received any antiretroviral treatment before entering the study.
- Patients who received Single dose nevirapine or any duration of AZT for PMTC will not be considered ARV naïve.
Key exclusion criteria (10 listed)
- Pregnancy and breast-feeding.
- Active neoplasia or previous history of neoplasia. (Except localized non visceral Kaposi´s Sarcoma; localized squamous or basal cell carcinoma of the skin, or intraepithelial cervical neoplasia grade III or less).
- Use of the following drugs within 180 days prior to study entry: systemic cancer chemotherapy, systemic investigational agents, and immunomodulators (growth factors, immune globulin, interleukins, interferons).
- Use of systemic corticosteroids in the last 2 weeks prior to randomization.
- Decompensated liver disease (defined as stage C of Child-Pugh classification) at the beginning of the 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 |
|---|---|---|
| maravirocAlso: Selzentry, Stocrin, TruvadaMaraviroc 600mg po BID every day from the entry visit until week 48 or until IRIS event or unacceptable toxicity develops. Efavirenz 600 mg qd every day from the entry visit until week 48 or until IRIS event or unacceptable toxicity develops. Tenofovir/Emtricitabine 300/200 mg qd from the entry visit until week 48 or until IRIS event or unacceptable toxicity develops. | Drug | Maraviroc |
| PlaceboAlso: Stocrin, TruvadaPlacebo tablets po BID every day from the entry visit until week 48 or until IRIS event or unacceptable toxicity develops. Efavirenz 600 mg qd every day from the entry visit until week 48 or until IRIS event or unacceptable toxicity develops. Tenofovir/Emtricitabine 300/200 mg qd from the entry visit until week 48 or until IRIS event or unacceptable toxicity develops. | Drug | Placebo |
Primary outcome
Time to occurrence of an IRIS event
Time frame: The initial 24 week period of observation
19 secondary outcomes
Time to occurrence of a severe IRIS event
Time frame: The initial 24 week period of observation
Occurrence of either an IRIS event or death
Time frame: By 24 and 48 weeks
Proportion of subjects who develops an IRIS case
Time frame: By week 24
Proportion of subjects who develop a severe IRIS case
Time frame: Week 24
Proportion of subjects who develop a confirmed, non dermatologic IRIS case
Time frame: Week 24
Proportion of subjects who develop an unmasking or paradoxical IRIS event
Time frame: Week 24
Frequency of cardiovascular, cerebrovascular, non AIDS related neoplasia, cirrhosis, renal failure and death in both treatment arms
Time frame: During the study (from entry to week 60)
Frequency of AIDS defining events and AIDS related events in both arms of treatment
Time frame: From basline to study end
General survival
Time frame: At week 24 and 48
Survival without IRIS
Time frame: At weeks 24 and 48
Proportion of patients with VL<50 copies/mL
Time frame: At weeks 8, 24 and 48
Changes form baseline in CD4+ cells count
Time frame: From baseline to weeks 12, 24 and 48
Safety and tolerability of the treatment regimens
Time frame: Along the study
Incidence of HIV drug resistance
Time frame: Baseline to week 60
Prevalence of CCR5 tropism
Time frame: Baseline
Prevalence of CCR5 HIV tropism
Time frame: At virological failure occurrence
Baseline predictors of IRIS
Time frame: Baseline
Genetic polymorphisms associated with the occurrence of IRIS
Time frame: Baseline
To evaluate the rol of biomarkers (CRP) in predicting or identifying IRIS and the effect of Maraviroc on this marker
Time frame: Baseline to IRIS event
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Nov 2012.
- Background: PubMed 15090834Jensen-Fangel S, Pedersen L, Pedersen C, Larsen CS, Tauris P, Moller A, Sorensen HT, Obel N. Low mortality in HIV-infected patients starting highly active antiretroviral therapy: a comparison with the general population. AIDS. 2004 Jan 2;18(1):89-97. doi: 10.1097/00002030-200401020-00011.
- Background: PubMed 17195766Corey DM, Kim HW, Salazar R, Illescas R, Villena J, Gutierrez L, Sanchez J, Tabet SR. Brief report: effectiveness of combination antiretroviral therapy on survival and opportunistic infections in a developing world setting: an observational cohort study. J Acquir Immune Defic Syndr. 2007 Apr 1;44(4):451-5. doi: 10.1097/QAI.0b013e31802f8512.
- Background: PubMed 11424971Lederman MM. Immune restoration and CD4+ T-cell function with antiretroviral therapies. AIDS. 2001 Feb;15 Suppl 2:S11-5. doi: 10.1097/00002030-200102002-00003.
- Background: PubMed 16551345Lawn SD, Myer L, Bekker LG, Wood R. CD4 cell count recovery among HIV-infected patients with very advanced immunodeficiency commencing antiretroviral treatment in sub-Saharan Africa. BMC Infect Dis. 2006 Mar 21;6:59. doi: 10.1186/1471-2334-6-59.
- Background: PubMed 16631548Battegay M, Nuesch R, Hirschel B, Kaufmann GR. Immunological recovery and antiretroviral therapy in HIV-1 infection. Lancet Infect Dis. 2006 May;6(5):280-7. doi: 10.1016/S1473-3099(06)70463-7.
- Background: PubMed 17488505Murdoch DM, Venter WD, Van Rie A, Feldman C. Immune reconstitution inflammatory syndrome (IRIS): review of common infectious manifestations and treatment options. AIDS Res Ther. 2007 May 8;4:9. doi: 10.1186/1742-6405-4-9.
- Background: PubMed 9204894Autran B, Carcelain G, Li TS, Blanc C, Mathez D, Tubiana R, Katlama C, Debre P, Leibowitch J. Positive effects of combined antiretroviral therapy on CD4+ T cell homeostasis and function in advanced HIV disease. Science. 1997 Jul 4;277(5322):112-6. doi: 10.1126/science.277.5322.112.
- Background: PubMed 15750393Shelburne SA, Visnegarwala F, Darcourt J, Graviss EA, Giordano TP, White AC Jr, Hamill RJ. Incidence and risk factors for immune reconstitution inflammatory syndrome during highly active antiretroviral therapy. AIDS. 2005 Mar 4;19(4):399-406. doi: 10.1097/01.aids.0000161769.06158.8a.
- Background: PubMed 16905787Lederman MM, Penn-Nicholson A, Cho M, Mosier D. Biology of CCR5 and its role in HIV infection and treatment. JAMA. 2006 Aug 16;296(7):815-26. doi: 10.1001/jama.296.7.815.
- Background: PubMed 16329283Westby M, van der Ryst E. CCR5 antagonists: host-targeted antivirals for the treatment of HIV infection. Antivir Chem Chemother. 2005;16(6):339-54. doi: 10.1177/095632020501600601.
- Background: PubMed 11873004Knobel H, Alonso J, Casado JL, Collazos J, Gonzalez J, Ruiz I, Kindelan JM, Carmona A, Juega J, Ocampo A; GEEMA Study Group. Validation of a simplified medication adherence questionnaire in a large cohort of HIV-infected patients: the GEEMA Study. AIDS. 2002 Mar 8;16(4):605-13. doi: 10.1097/00002030-200203080-00012.
- Background: PubMed 11737333French MA, Lenzo N, John M, Mallal SA, McKinnon EJ, James IR, Price P, Flexman JP, Tay-Kearney ML. Immune restoration disease after the treatment of immunodeficient HIV-infected patients with highly active antiretroviral therapy. HIV Med. 2000 Mar;1(2):107-15. doi: 10.1046/j.1468-1293.2000.00012.x.
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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.
Ian Sanne, MBBCH, FCP principal investigator
University of the Witwatersrand. Themba Lethu Clinic.
Michael M. Lederman, MD principal investigator
Center for AIDS Research. Case Western Reserve University
Luis J Montaner, M.Sc. principal investigator
HIV-1 Immunopathogenesis Laboratory. The Wistar Institute
10 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing maraviroc in people with Immune Reconstitution Inflammatory Syndrome and HIV, run by Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran at 10 sites in 3 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 19 inclusion and 10 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: status not confirmed, as of the sponsor's last update on 27 Nov 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Mexico, United States, South Africa. 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. Some participants in this study may receive a placebo. 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?
Results are not available in the source record.
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?
Time to occurrence of an IRIS event (time frame: The initial 24 week period of observation). 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 NCT00988780, which also lists 45 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 27 Nov 2012.