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Background: The OK04 trial has shown that 48 weeks of lopinavir-ritonavir monotherapy with reintroduction of nucleosides as needed was noninferior to continuation of triple therapy with 2 nucleosides and lopinavir-ritonavir in patients with prior stable suppression. However, it is still uncertain if this experimental strategy can maintain suppression in the long term., Methods: Patients entered this noninferiority trial (upper limit 95% confidence interval: +12%) with no history of virological failure while receiving a protease inhibitor and receiving 2 nucleosides plus lopinavir/ritonavir, with HIV RNA <50 copies per milliliter for more than 6 months. Primary end point was percent of patients without therapeutic failure, defined as confirmed HIV RNA >500 copies per milliliter with exclusion of monotherapy patients who resuppressed to <50 copies per milliliter after resuming baseline nucleosides, or loss to follow-up, or change of randomized therapy other than reinduction., Results: Through 96 weeks, percentage of patient without therapeutic failure was 87% (monotherapy, n = 100) vs. 78% (triple therapy, n = 98; 95% confidence interval: -20% to +1.2%). Percentage with HIV RNA <50 copies per milliliter (intention to treat, missing = failure, reinduction = failure): 77% (monotherapy) vs. 78% (triple therapy). Low-level viral rebound was more frequent in the monotherapy group. Twelve patients in the monotherapy group (12%) needed reinduction with nucleosides. Discontinuations due to adverse events were significantly more frequent in the triple therapy group (8%) than in the monotherapy group (0%); P = 0.003., Conclusions: At 96-week lopinavir/ritonavir monotherapy with reintroduction of nucleosides as needed was noninferior to continuation of triple therapy. Incidence of adverse events leading to treatment discontinuation was significantly lower with monotherapy. (ClinicalTrials.gov number, NCT00114933).

Background: Risk factors for loss of virological response in patients receiving lopinavir/ritonavir (LPV/r) monotherapy as maintenance treatment have not been determined., Methods: In 121 patients enrolled in the OK and OK04 clinical trials assigned to receive monotherapy with LPV/r, we attempted to identify factors associated with loss of virological suppression at 48 weeks, defined as confirmed serum HIV type-1 RNA>50 copies/ml, with missing data or changes caused by toxicity censored. Univariate and multivariate Cox proportional hazard models were used to calculate hazard ratios for the risk of loss of virological suppression., Results: At week 48, 15 patients experienced loss of virological suppression. Probability of loss of virological suppression was 12.7%. Less than 9 months of maintenance of virological suppression prior to monotherapy, a lower baseline haemoglobin and low adherence measured by self-reported total missed doses in the week prior to study visit were associated with loss of virological suppression in the univariate analyses. Independent factors associated with loss of virological suppression by multivariate analyses were > or =2 visits with self-reported missed doses in the week prior to the study visit, a lower baseline haemoglobin and a nadir CD4(+) T-cell count <100 cells/microl., Conclusions: Suboptimal adherence, lower baseline haemoglobin and a nadir CD4(+) T-cell count <100 cells/microl were the main risk factors for losing virological suppression in patients randomized to monotherapy with LPV/r.

Objectives: Data are scarce on the long-term efficacy of lopinavir/ritonavir monotherapy for the maintenance of HIV suppression. Four years of results of patients randomized to monotherapy in the Only Kaletra (OK) pilot clinical trial are presented., Patients and Methods: Twenty-one HIV-infected patients with suppressed HIV replication (<50 copies/mL) for at least 6 months and without previous failure while receiving a protease inhibitor-based regimen started lopinavir/ritonavir monotherapy. Follow-up was performed within the OK pilot clinical trial during the first 2 years and according to routine clinical practice during the 3rd and 4th years., Results: Fourteen patients (67%) remain on monotherapy and with RNA <50 copies/mL (intention-to-treat analysis, with missing patients scored as failures). Five patients (24%) had virological rebound and all of them were successfully re-suppressed by adding two nucleosides. No major protease inhibitor mutations were found., Conclusions: Our data support the long-term efficacy and safety of lopinavir/ritonavir monotherapy for the maintenance of HIV suppression, a finding that must be confirmed in larger studies.

Background: Prior attempts to reduce the number of drugs needed to maintain viral suppression in patients with suppressed HIV replication while receiving three antiretroviral drugs have been unsuccessful., Methods: In 205 patients with suppressed HIV replication on lopinavir-ritonavir and two nucleosides, this randomized, open-label, non-inferiority clinical trial compared the strategies of continuation of triple therapy versus lopinavir-ritonavir monotherapy followed by reinduction with two nucleosides if virological rebound occurred without genotypic resistance to lopinavir-ritonavir. The primary endpoint was proportion of patients without therapeutic failure, defined as confirmed HIV RNA higher than 500 copies/mL (with exclusion of patients receiving monotherapy who resuppressed to < 50 copies/mL after resuming baseline nucleosides), or loss to follow-up, or change of randomized therapy other than reinduction., Results: At week 48, the percentage of patients without therapeutic failure was 94% in the monotherapy group versus 90% in the triple therapy group (difference,-4%; upper limit of 95% confidence interval for difference, 3.4%). The percentage of patients with HIV RNA 50 copies/mL at 48 weeks by intention-to-treat, missing data or reinductions considered as failures, were 85% in the monotherapy group versus 90% in the triple therapy group (P = 0.31; 95% upper limit of 95% confidence interval for difference, 14%)., Conclusion: In this trial, 48 weeks of lopinavir-ritonavir monotherapy with reintroduction of nucleosides as needed was non-inferior to continuation of two nucleosides and lopinavir-ritonavir in patients with prior stable suppression. However, episodes of low level viremia were more common in patients receiving monotherapy.

Objective: This study evaluated maintenance with lopinavir/ritonavir monotherapy vs. continuing lopinavir/ritonavir and 2 nucleosides in HIV-infected patients with suppressed HIV replication., Design: Randomized, controlled, open-label, multicenter, pilot clinical trial., Methods: Adult patients were eligible if they had no history of virologic failure while receiving a protease inhibitor, were receiving 2 nucleosides + lopinavir/ritonavir (400/100 mg b.i.d.) for >1 month and had maintained serum HIV RNA <50 copies/mL for >6 months prior to enrollment., Results: Forty-two patients were randomly assigned 1:1 to continue or stop the nucleosides. At baseline there were no significant differences between groups in median CD4 cells/muL (baseline or nadir), pre-HAART (highly active antiretroviral therapy) HIV log10 viremia, or time with HIV RNA <50 copies/mL prior to enrollment. After 48 weeks of follow-up, percentage of patients remaining at <50 HIV RNA copies/mL (intention to treat, M = F) was 81% for the monotherapy group (95% CI: 64% to 98%) vs. 95% for the triple-therapy group (95% CI: 86% to 100%); P = 0.34. Patients in whom monotherapy failed had significantly worse adherence than patients who remained virally suppressed on monotherapy. Monotherapy failures did not show primary resistance mutations in the protease gene and were successfully reinduced with prerandomization nucleosides. Mean change in CD4 cells/microL: +70 (monotherapy) and +8 (triple) (P = 0.27). Mean serum fasting lipids remained stable in both groups. No serious adverse events were observed., Conclusion: Most of the patients maintained with lopinavir/ritonavir monotherapy remain with undetectable viral load after 48 weeks. Failures of lopinavir/ritonavir monotherapy were not associated with the development of primary resistance mutations in the protease gene and could be successfully reinduced adding back prior nucleosides.