Intermittent ART in Primary HIV Infection

Phase 4

Completed

• Conditions: HIV
• Interventions: Drug: Antiretroviral therapy plus Interleukin-2; Drug: Antiretroviral therapy alone

• Registration Number: NCT02300623
• Lead Sponsor: Juan A. Arnaiz

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.

Study Timeline

• Study Start: 2000-03
• Primary Completion: 2013-04
• Study Completion: 2013-04
• Status Verified: 2014-11
• Study First Submitted: 2014-11-18
• Study First Submitted QC: 2014-11-21
• Last Update Submitted: 2014-11-21
• Study First Posted: 2014-11-25
• Last Update Posted: 2014-11-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment	Antiretroviral therapy plus Interleukin-2	Antiretroviral therapy plus Interleukin-2'
Control	Antiretroviral therapy alone	Antiretroviral therapy alone

Primary Outcome Measures

Name	Time	Method
Control of viral replication without ART.	48 weeks

Secondary Outcome Measures

Name	Time	Method
Time to resume ART.	9 years after final stop

Trial Locations

Locations (1)

Hospital Clinic de Barcelona; 🇪🇸 Barcelona, Spain