HIV-1 Infections
Conditions
Keywords
Primary HIV-1 infection, antiretroviral treatment, HIV reservoirs, HIV-DNA levels, randomized, Treatment Naive
Brief summary
The purpose of this trial is to assess the impact of raltegravir, maraviroc, darunavir/r, and Truvada® (emtricitabine/tenofovir) vs. darunavir/r and Truvada® on cell-associated HIV-DNA levels in patients with primary HIV-1 infection.
Detailed description
Primary HIV-1 infection is characterized by a phase of intense replication, with a quick dissemination and early changes in the immune system. During primary HIV-1 infection, damages to MALT and GALT promotes a chronic cell activation, which participates in a progressive decay of immune functions. After HAART initiation, the magnitude and rapidity of cell-associated HIV-DNA decrease are significantly higher in patients with primary HIV-1 infection than in patients with chronic infection (Ngo Giang Huong, AIDS 2004). We hypothesize that an early intervention at different levels of viral replication with potent and well-tolerated new drugs may have a greater impact on cell-associated HIV-DNA levels than conventional triple-drug HAART.
Interventions
DRUGraltegravir; maraviroc; darunavir; ritonavir; tenofovir/emtricitabine
raltegravir (Isentress®): 400 mg bid. maraviroc (Celsentri®): 150 mg bid. darunavir (Prezista®): 800 mg QD. ritonavir tablet (Norvir®): 100 mg QD. tenofovir/emtricitabine (Truvada®): one 245/200 mg tablet QD.
DRUGdarunavir; ritonavir; emtricitabine/tenofovir
darunavir (Prezista®): 800 mg QD. ritonavir tablet (Norvir®): 100 mg QD. tenofovir/emtricitabine (Truvada®): one 245/200 mg tablet QD.
Sponsors
Gilead Sciences
Merck Sharp & Dohme LLC
Pfizer
Janssen-Cilag Ltd.
ANRS, Emerging Infectious Diseases
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with acute or primary HIV-1 infection * Acute infection: negative or slightly positive Elisa, with negative or incomplete western-blot (0 or 1 antibody) and positive HIV-RNA and/or positive Ag p24. * Primary infection: positive Elisa with incomplete Western-blot (≥ 2 and \< 5 antibodies with the presence of anti-p24 antibodies associated with an anti-gp160 or an anti-gp120 or an anti-gp41antibody) and positive HIV-RNA. * Symptomatic Primary infection or CD4 \<500/mm3 * written informed consent * ≥ 18 years old
Exclusion criteria
* Prior post exposure antiretroviral treatment within six months before enrolment * Pregnancy or breast-feeding * HIV-2 infection * Current malignancy * Prothrombin time \< 50% * Creatinine clearance \< 60 ml/min * ASAT, ALAT or bilirubin ≥10\*N * Platelets \< 25000/mm3
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To compare the 24-month impact of maximized vs. conventional HAART- on HIV reservoirs, as assessed by cell-associated HIV-DNA levels, in patients with acute or primary HIV-1 infection | 24 months |
Secondary
| Measure | Time frame |
|---|---|
| Plasma HIV-RNA levels and proportion of patients with plasma viral load < 5 copies/ml at M24 | 24 months |
| Changes in cell-associated HIV-DNA between baseline and M24 | 24 Months |
| Plasma HIV-RNA levels and proportion of patients with plasma viral load < 50 copies/ml at M12, M24 and M30 | 30 months |
| Tolerability of trial treatments | 24 months |
| Number and type of ARV mutations in virological failures and change in CCR5 tropism | 24 Months |
| Evolution of the CD4 and CD8 between D0 and M24 | 24 months |
Countries
France
Outcome results
None listed