Reported by Jules Levin
11th EACS, Oct 24-27, 2007 Madrid Spain
Pulido F1, Arribas J.R2, Delgado R3, Gonzlez-Garc'a J2, P_rez-Valero I2, Arranz A4, Miralles P5, Hernando A1,6.
BACKGROUND
There is no data about the long-term efficacy of lopinavir/r monotherapy for maintenance of HIV suppression.
The OK pilot clinical trial evaluated maintenance with lopinavir/r monotherapy vs continuing lopinavir/r and 2 nucleosides in HIV-infected patients with suppressed HIV replication.
For the present analysis we report 4 years follow-up of patients randomized to LPV/r monotherapy in the OK pilot clinical trial.
AUTHOR CONCLUSIONS
After 4 years of follow-up most patients on LPV/r remain virologically suppressed.
No patient with loss of suppression has developed protease inhibitor mutations and no patient has changed LPV/r due to virological failure.
Most virological rebounds took place early and were probably related to lack of adherence.
This study supports the long-term efficacy and safety of LPV/r monotherapy for maintenance of HIV suppression.
METHODS
Patients were eligible for the OK pilot clinical trial if they had no history of virological failure while receiving a protease inhibitor, were receiving nucleosides and LPV/r and had plasma HIV-RNA <50 c/ml for at least 6 months.
Patients with confirmed virological rebound (>50 c/ml) while on LPV/r monotherapy without genotypic resistance to lopinavir were re-intensified with baseline nucleosides.
After the end of the trial extension (96 weeks), all patients remaining in monotherapy with LPV/r opted to continue treatment with LPV/r monotherapy and were followed-up according to routine clinical practice in Spain (every 3-6 months).
RESULTS
21 patients were randomized to LPV/r monotherapy.
Four years after randomization, 14 patients (66.7%) remain with virological suppression (HIV-RNA <50 C/ML) on monotherapy. Figure 3
Five patients (24%) had a virological rebound during follow-up (weeks 16, 16, 24, 96, 128) and all of them were successfully re-suppressed addingf 2 nucleosides:
--4 remain suppressed with LPV/r + 2 nucleosides (follow-up after reimduction: 168, 165, 160, 51 weeks)
--1 patient was lost to follow-up after re-suppression
--in 4/5 patients with virological rebound bad adherence episodes could be demonstrated
One patient on discontinued monotherapy and was lost to followup.
One patient died at week 84 while suppressed on monotherapy, due to respiratory failure secondary to chronic bronchopathy not AIDS related.
Genotypic resistance tests were performed in 9 samples from 5 patients (4 patients with loss of virological suppression; 1 patient who discontinued therapy). No major protease inhibitor mutations were present in the genotypes. A genotypic test could not be performed in 1 patient with virological rebound as HIV-RNA remained <500 c/ml during the episode of loss of virological suppression.
Median increase in cd4 cell count for patients still receiving monotherapy was 223.
References
1., Arribas JR, Pulido F, Delgado R, et al. Lopinavir/ritonavir as single-drug therapy for maintenance of HIV-1 viral suppression: 48 week results of a randomized, controlled, open-label, proof-of-concept pilot clinical trial (OK Study). J Acquired Immune Defic Syndr. 2005;40:280-287.
Financial support: the OK Study supported with an unrestricted grant from Abbott Labs.
