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

NCT ID: NCT00979706

Last Updated: 2014-11-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-03-31
• Study Completion Date: 2014-11-30

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.

Conditions

HIV

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

HAART

Patients assigned to this arm will receive standard HAART

Group Type: ACTIVE_COMPARATOR

HAART

Intervention Type: DRUG

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.

HAART + Immunotherapy

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.

Group Type: EXPERIMENTAL

HAART + Immunotherapy

Intervention Type: DRUG

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.

Interventions

HAART

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.

Intervention Type: DRUG

HAART + Immunotherapy

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.

Intervention Type: DRUG

Other Intervention Names

Viread; Epivir; Kaletra; Cyclosporine A; GM-CSF; Peg-IFN; Interleukin-2

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Juan A. Arnaiz

OTHER

Sponsor Role: lead

Responsible Party

Juan A. Arnaiz

MDPhD

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Josep Maria Miró, MDPhD

Role: PRINCIPAL_INVESTIGATOR

Hospital Clinic of Barcelona

Locations

Hospital Clinic de Barcelona

Barcelona, Barcelona, Spain

Countries

Spain

References

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.

Reference Type: DERIVED

PMID: 27999018 (View on PubMed)

Other Identifiers

PHI-INMUNOMEDIADO

Identifier Type: -

Identifier Source: org_study_id