Strategic Long Term, Immunologically Driven Treatment Interruptions in Patients on Effective HAART: a Controlled, Randomized Study
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Enrollment
- 130
- Locations
- 1
- Primary Endpoint
- Proportion of subjects maintaining at each time-point a CD4 + cell count above 400 cells/mcL.
Study Overview
Brief Summary
This is a single center, independent study. The primary objective is to compare efficacy and safety of continuing a conventional HAART in chronically infected HIV patients with a therapeutic strategy based on long term, immunologically driven treatment interruptions. Evaluation will be based on clinical, immunological and virological response.
Patients will be randomized in a ratio 1:2 to one of the two treatment arms:
Control group continuing the ongoing therapy STI group performing long term CD4 guided structured treatment interruptions In the STI arm patients will stay off therapy until their CD4 count will drop < 400 cells/mcL. At that time point patients will resume the HAART regimen they were assuming before STI and will continue HAART until they CD4 count will raise > 800 cells/mcL and their HIV-RNA will drop below the detection limit of 50 copies/ml. When both the CD4 count and the viral load will be within these pre-set values they will stop therapy again. There is no limit to the number of interruptions and re-start cycles during the study period The study is powered to evaluate equivalence between the two strategies under the assumption of a failure proportion in the control arm at each time point not greater than 5% and a maximum allowed difference of 15%.
Detailed Description
Study objectives
Primary objective of the study is:
To compare efficacy (clinical and immunological) and safety of continuing a conventional HAART in chronically infected HIV patients with a therapeutic strategy based on long term, immunologically driven treatment interruptions. To verify the risk of developing viral resistance
Secondary objectives are:
To verify the effect of the two strategies on metabolic parameters To verify the possibility to steadily discontinue antiretroviral therapy in patients that started it with baseline immunological values higher than those currently recommended by international guidelines for HIV treatment To identify predictive variables of the possibility to safely discontinue antiretroviral therapy To verify the dynamic of CD4 + loss and HIV replication after treatment interruption To verify costs connected to the strategy
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •i. Age > 17 years ii. Informed consent signed iii. Effective ongoing treatment (HIV-RNA < 50 copies/ml). Treatment must be based on any triple drug therapy. Patients must be on the same steady therapy for at least 3 months.
- •iv. Current CD4 cell count above 800 cells/L
Exclusion Criteria
- •i. Childbearing or breastfeeding. Women of childbearing potential will be asked to adopt effective contraceptive methods or behaviors ii. Any ongoing grade 4 (WHO) AE or laboratory abnormality with the exclusion of cholesterol, triglycerides for which a grade 3 (AHA) level will be considered an exclusion criteria.
- •iii. Previous use of immunomodulatory agents
Outcomes
Primary Outcomes
Proportion of subjects maintaining at each time-point a CD4 + cell count above 400 cells/mcL.
Occurrence of clinical end-points (AIDS defining event and death)
Virologic failure with the selection of resistance conferring mutations.
Secondary Outcomes
- Mean variation of blood cholesterol and triglycerides from baseline values. For these parameters the proportion of subjects with a value above grade 2 (AHA) will be also used as evaluation criteria.
- Development of lipodystrophy or modification of a pre-existing lipodystrophy
- Time off therapy
- Economic evaluation
- Genotypic tests to be performed in the case of HIV-RNA > 1000 copies/ml while on therapy for at least 4 months or one month after each treatment interruption.