AIDS, HIV-1 Infection
Conditions
Keywords
Late diagnosed HIV-1 infected patients, AIDS-defining events, Immune restoration
Brief summary
The objective of the OPTIMAL study is to demonstrate that the adjunction of Maraviroc to a combination of antiretroviral therapy in naive and late diagnosed HIV-1 infected patients counts may accelerate the kinetics of immune restoration and decrease the risk of disease progression and death. It is a randomized, versus placebo, double-blind trial, conducted in France, Spain and Italy.
Interventions
DRUGMaraviroc (Celsentri)
Patients will take cART optimized regimen according to the recommended regimen as first line of treatment in most commonly used guidelines with Maraviroc at the following dose: 150 mg orally twice a day for patients receiving a Protease Inhibitor Ritonavir-boosted regimen (except Fosamprenavir), 300 mg orally twice a day for patients receiving a Fosamprenavir Ritonavir-boosted regimen or 600 mg orally twice a day for patients receiving Efavirenz-based regimen. Duration: 72 weeks.
DRUGPlacebo
Patients will take cART optimized regimen according to the recommended regimen as first line of treatment in most commonly used guidelines with Placebo at the following dose: 150 mg orally twice a day for patients receiving a Protease Inhibitor Ritonavir-boosted regimen (except Fosamprenavir), 300 mg orally twice a day for patients receiving a Fosamprenavir Ritonavir-boosted regimen or 600 mg orally twice a day for patients receiving Efavirenz-based regimen. Duration: 72 weeks.
Sponsors
Pfizer
ANRS, Emerging Infectious Diseases
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed HIV-1 infection (ELISA and Western Blot tests positive) * CD4+ T lymphocytes below or equal 200/mm³ or previous AIDS-defining-illness at diagnosis * Patient naïve from any antiretroviral * In women, use of a contraceptive method, and lack of actual pregnancy * Patients with a coverage from social health * After informed consent
Exclusion criteria
* Current pregnancy, lack of contraceptive method, breast-feeding * Current active tuberculosis (either suspected, diagnosed) * Ongoing malignancies except cutaneous Kaposi's sarcoma. Patients with a previous cancer considered as cured for at least 6 months could be included in the study * Current or previous severe cardiac failure, chronic respiratory disease, renal or liver insufficiency; any life-threatening organ failure * Cognitive impairment, psychiatric disorders, severe depressive affects, unadapted behavior * Use of cytostatic drugs, immunosuppressive agents, steroids * PMN (polymorphonuclear neutrophil) below 750/mm³, platelets below 50,000/mm³, haemoglobin below 10 g/dL; ASAT (aspartate aminotransferase), ALAT (alanine aminotransferase) or bilirubin over 2.5 ULN; lipase over 2 ULN (Upper limit of normal), serum creatinine over 1.5 ULN; proteinuria over 1g/L; INR (International Normalized Ratio) abnormal * Current or previous, during the 3 last months, use of immunomodulatory agents (G-CSF (granulocyte colony stimulating factor), IL-2 (Interleukin-2), GM-CSF (Granulocyte Macrophage colony stimulating factor), interferons, pentoxifylline) * Hypersensitivity to peanut and /or soy products
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To demonstrate the clinical benefit of the adjunction of Maraviroc to a combination of antiretroviral therapy defined as decrease of clinical events | From Week 0 to Week 72 | The clinical benefit is the reduction of occurence of a composite outcome consisting of: * New AID-defining event (1993 CDC(Centers for Disease Control) expanded surveillance definition) * Non B or C events (Aspergillosis, Bartonellosis, Chagas disease, Leishmaniasis, Lymphoma, Microsporidiosis chronic intestinal, Nocardiosis, Penicillium marneffei extrapulmonary, Pneumocystis jiroveci extrapulmonary, Rhodococcus equi disease, Severe bacterial infections) * Serious non-AIDS events (Cardiovascular disease, Chronic end stage renal disease, Liver failure, Non-AIDS defining cancers, IRIS) * All cause of mortality |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety evaluation and Clinical, Immunological and pharmacological evaluation | From Week 0 to Week 72 | The secondary end points: * Clinical events (to compare Maraviroc and placebo arm for each component of the primary composite endpoint and other major outcomes) * Immunological evaluation (T cells phenotypic analysis; seric markers of immune activation) * Virological evaluation (plasma HIV viral load analysis; viral tropism testing,) * Pharmacokinetic evaluation (plasma concentration of Maraviroc and relationship with virological response) * Clinical and biological safety of the strategy (Adverse events \>= grade 2 on ANRS scale of adverse event) * Cost-effectiveness analysis |
Countries
France
Outcome results
None listed