Immune-based Therapy Pilot Study for the Treatment of Primary HIV Infection (PHI-IMD).

Study Overview
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Brief Summary
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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
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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.

Official Title
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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)

Conditions
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HIV

Intervention / Treatment
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* Drug: HAART
* Drug: HAART + Immunotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV-infected patients (age 18 years or over) with primary HIV infection <90 days. Giving written informed consent to participate into the study. Exclusion Criteria: Patients not accepting to start HAART. Patients wishing start HAART treatment with nevirapine or efavirenz. Pregnant women or planning pregnancy. Intravenous drug user or alcohol abuse. Previous treatment with cyclosporin A, GM-CSF,pegylated-interferon-alpha o interleukine-2. Renal or liver failure. Any formal contraindication to treatment with the study drugs. Patients with a history of psychiatric disorder, thyroid illness, dislipidemia requiring treatment, cardiovascular disease, arterial hypertension, or diabetes mellitus. In treatment with drugs interacting with study drugs. Acute infection for HTLV-I or EBV.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: HAART<br>Patients assigned to this arm will receive standard HAART | Drug: HAART<br>* Patients assigned to this arm will receive Trizivir and kaletra. After the first 9 months of HAART, all patients will stop HAART until HIV viral load in plasma became detectable (>200 copies/mL). Then, they will re-start HAART plus low doses of IL-2 during 2 months. All patients will be followed-up during 1 year.<br>* Other names: Kaletra;|
| Experimental: HAART + Immunotherapy<br>Patients assigned to this arm will receive HAART plus cyclosporin A during the first two months and after that will receive IFN, GM-CSF and IL-2. | Drug: HAART + Immunotherapy<br>* Patients assigned to this arm will receive Trizivir + Kaletra + cyclosporin A during the first two months. This group also will receive GM-CSF plus pegylated-interferon-alpha until HIV viral load in plasma became detectable (>200 copies/mL). Then, they will re-start HAART plus low doses of IL-2 during 2 months. At this moment they will stop HAART. All patients will be followed-up during 1 year.<br>* Other names: Interleukin-2;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients remaining below 5,000 copies/mL at 12 and 48 weeks after stoping HAART. |  | W12 y W48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adherence to treatment |  | W8, W24, W36, W96 | 
| CD4, CD8 |  | W8, W24, W36, W96 | 
| Specific HIV immune responses (CD4 and CTL) |  | W8, W24, W36, W96 | 
| Proportion of patients PVL (plasma viral load)<40 |  | W8, W24, W36, W96 | 
| Adverse events |  | W8, W24, W36, W96 |