Clinical trial NCT00979706: Immune-based Therapy Pilot Study for the Treatment of Primary HIV Infection (PHI-IMD).
Official title: Immune-based Therapy Pilot Study for the Treatment of Primary HIV Infection With the Objective to Induce a Strong Specific HIV Immune Response Able to Control Viral Replication Without Highly Active Anti-Retroviral Therapy (HAART)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV
Lead sponsor: Hospital Clinic of Barcelona
Sponsor class: OTHER
First posted: 2009-09-18
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Pilot study for the treatment of primary HIV infection with the objective to induce a strong specific HIV immune response able to control viral replication without HAART.

Detailed description: Pilot and open RCT in 20 patients with primary HIV-1 infection who were randomized to one of these two arms: 1) Control arm (A), Tenofovir +Lamivudine + Lopinavir-ritonavir (Kaletra) at standard doses for 44 weeks (W44); a short treatment interruption (TI) was performed at W36, and HAART was restarted for 8 weeks when plasma HIV-1 RNA viral load (pVL) rebounded\>200 copies/mL. At W44 HAART was stopped and patients were followed for 48 additional weeks (W92). 2) Immune-based arm (B), same HAART schedule plus oral cyclosporine A (CsA)(serum levels 250-350 mcg/L) for the first 8 weeks of HAART. During the TI, patients received sc GM-CSF (250 mcg TIW) plus weekly sc pegylated-interferon a2b (Peg-INF)(1.5 mcg/kg/week). During the last 8 weeks of HAART (until W44), patients received daily sc low-dose interleukin-2 (IL-2)(0.75 MU/kg QD). The primary endpoint was pVL \<1000copies/mL (\<3.0 log10/mL) at 12 (W56) and at 48 (W92) weeks after stopping HAART. Sample size was calculated in order to detect a pVL difference of 1.5log10 copies/mL at 12 (W56) weeks after stopping HAART between the control and the immune-based arms with a power of 80% and a level of significance of0.05.

Eligibility criteria: Inclusion Criteria:

1. HIV-infected patients (age 18 years or over) with primary HIV infection \<90 days.
2. Giving written informed consent to participate into the study.

Exclusion Criteria:

1. Patients not accepting to start HAART. Patients wishing start HAART treatment with nevirapine or efavirenz.
2. Pregnant women or planning pregnancy.
3. Intravenous drug user or alcohol abuse.
4. Previous treatment with cyclosporin A, GM-CSF,pegylated-interferon-alpha o interleukine-2.
5. Renal or liver failure.
6. Any formal contraindication to treatment with the study drugs.
7. Patients with a history of psychiatric disorder, thyroid illness, dislipidemia requiring treatment, cardiovascular disease, arterial hypertension, or diabetes mellitus.
8. In treatment with drugs interacting with study drugs.
9. Acute infection for HTLV-I or EBV.

Primary outcomes:
measure: Proportion of patients remaining below 5,000 copies/mL at 12 and 48 weeks after stoping HAART.
timeFrame: W12 y W48
Secondary outcomes:
measure: Adherence to treatment
timeFrame: W8, W24, W36, W96
measure: CD4, CD8
timeFrame: W8, W24, W36, W96
measure: Specific HIV immune responses (CD4 and CTL)
timeFrame: W8, W24, W36, W96
measure: Proportion of patients PVL (plasma viral load)<40
timeFrame: W8, W24, W36, W96
measure: Adverse events
timeFrame: W8, W24, W36, W96
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
Study officials:
affiliation: Hospital Clinic of Barcelona
name: Josep Maria Miró, MDPhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Nicolas D, Ambrosioni J, Sued O, Brunet M, Lopez-Dieguez M, Manzardo C, Aguero F, Tuset M, Plana M, Guardo AC, Mosquera MM, Munoz-Fernandez MA, Caballero M, Marcos MA, Gatell JM, de Lazzari E, Gallart T, Miro JM. Cyclosporine A in addition to standard ART during primary HIV-1 infection: pilot randomized clinical trial. J Antimicrob Chemother. 2017 Mar 1;72(3):829-836. doi: 10.1093/jac/dkw462.