Intermittent ART in Primary HIV Infection

NCT ID: NCT02300623

Last Updated: 2014-11-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-03-31
• Study Completion Date: 2013-04-30

Brief Summary

Interventions during primary HIV infection (PHI) can modify the immune control and the clinical evolution during the chronic phase. Although several studies suggest the benefit of antiretroviral treatment (ART) during PHI, indication of ART is still not universally recommended. The investigators randomized patients with PHI, with a favourable immunological profile and well controlled on ART, to undergone structured treatment interruptions alone or with low doses of IL-2, stopping ART thereafter. The endpoints were immune control of HIV replication and time to resume ART. Immunological profile, specific CD4 and CD8 responses and clinical data were analysed for both groups up to 48 weeks, and during a long follow-up, up to nine years since final ART stop.

Detailed Description

The study design included two phases. The first phase consisted in four STI of 8 weeks each (off-ART), separated by 16 weeks of treatment -or the time necessary to reach again to PVL <20 copies/mL- (on-ART). At the end of the 4th off-ART cycle (week 0) an interim evaluation was performed and the second phase initiated. During the second phase, the first 6 patients received ART until they reach PVL<20 copies/mL, discontinuing thereafter (final stop). The last 6 patients received ART and low doses of IL-2. ARV therapy was stopped after reaching PVL<20 copies/mL (final stop) and IL-2 after 6 months of treatment. IL-2 was prescribed at a dose of 750.000 UI/m2 daily and was self-administrated in all patients previous trained by a specialized nurse. ART was resumed in patient dropping CD4 cell count less than 350 cell/mm3 in two consecutive determinations or in patients who developed opportunistic infections. A long term follow up analysis was performed at 3, 6 and 9 years since the final stop. It included time to resume ART, clinical events, survival rate, CD4-CD8-CD4/CD8 ratio.

Conditions

HIV

Study Design

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

Study Groups

Control

Antiretroviral therapy alone

Group Type: ACTIVE_COMPARATOR

Antiretroviral therapy alone

Intervention Type: DRUG

Standard antiretroviral therapy

Treatment

Antiretroviral therapy plus Interleukin-2'

Group Type: EXPERIMENTAL

Antiretroviral therapy plus Interleukin-2

Intervention Type: DRUG

Daily s.c. IL-2: 750,000 UI/m2/day for 6 months

Interventions

Antiretroviral therapy plus Interleukin-2

Daily s.c. IL-2: 750,000 UI/m2/day for 6 months

Intervention Type: DRUG

Antiretroviral therapy alone

Standard antiretroviral therapy

Intervention Type: DRUG

Other Intervention Names

IL-2; Stavudine; Lamivudine; Indinavir; stavudine; Lamivudine; Indinavir

Eligibility Criteria

Inclusion Criteria

• PHI defined by detectable plasma viral load (PVL) or p24 antigen detection coupled with a negative or indeterminate LIA assay (according CDC criteria); negative HIV-1 EIA in the preceding 90 days or by a positive EIA and LIA assay with acute retroviral syndrome in the preceding 90 days of starting ART plus documented negative HIV-1 EIA within the previous year.
• ART started within 90 days from the HIV exposure and continuing in the same treatment at least 12 months before the inclusion, and they must have shown good virological and immunological responses, defined as undetectable PVL (<20 copies/mL in the last two controls) and CD4 more than 500 cells/mm3 with a CD4/CD8 ratio >1 in the last 8 months previous to enrolment

Exclusion Criteria

• Infection of more than 90 days.
• Age under 18 years old.
• AIDS defining condition

• 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

MD

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

Sued O, Ambrosioni J, Nicolas D, Manzardo C, Aguero F, Claramonte X, Plana M, Tuset M, Pumarola T, Gallart T, Gatell JM, Miro JM. Structured Treatment Interruptions and Low Doses of IL-2 in Patients with Primary HIV Infection. Inflammatory, Virological and Immunological Outcomes. PLoS One. 2015 Jul 17;10(7):e0131651. doi: 10.1371/journal.pone.0131651. eCollection 2015.

Reference Type: DERIVED

PMID: 26186440 (View on PubMed)

Other Identifiers

PHI-IL2

Identifier Type: -

Identifier Source: org_study_id