LOTTI study Centers
This a multicenter, multinational study.
Clinical phase: III
Objectives
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.
Secondary objectives are:
- To verify the risk of developing viral resistance
- To verify the effect of the two strategies on metabolic parameters
- To verify the possibility to steadily discontinue antiretroviral therapy in patients who
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+ cell loss and HIV replication after treatment interruption
Number of Patients: A total of 320 patients.
Study design:
Controlled, Randomized, Open study The study will last 5 years
Treatment arms:
Patients will be randomized in a ratio 1:1 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 <
350 cells/mcL (one measurement will be considered sufficient). 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 > 600 cells/mcL (at least 2 consecutive measurements 2 months
apart) and their HIV-RNA will drop below the detection limit of 50 copies/ml (one measurement
will be considered sufficient). 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
End points:
The primary end-point for the evaluation of the main objective of the study will be clinical.
The primary outcome measure will be based on the occurrence of a clinical end-point defined
as: disease progression (occurrence of any AIDS defining event), death for any cause or the
occurrence of clinical events requiring hospital admission
The secondary objectives of the study will be evaluated on the basis of:
- Mean variation of blood cholesterol and triglycerides from baseline values.
- Development of lipodystrophy or modification of a pre-existing lipodystrophy
- Time off therapy.
- Variation of CD4 counts and HIV-RNA levels
- 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.
Statistics:
The study is powered to evaluate equivalence between the two strategies under the assumption
that, in the control arm, the primary end-point would be observed in a proportion of subjects
< 7% and that the same proportion in the STI arm would not exceed 10% with a maximum allowed
95%CI of 12%. 320 patients will be needed for alfa = 5% and 1-beta = 80%. The primary
analysis will be made according to the intention-to-treat approach and therefore no
correction for eventual drop outs is needed. In addition, a secondary per-protocol analysis
will be performed.