A pilot, prospective, open-label simplification study to evaluate the safety, efficacy, and pharmacokinetics of once-daily lopinavir-ritonavir monotherapy in HIV-HCV coinfected patients: the MONOCO study.

BACKGROUND: A safe, effective, easy-to-dose antiretroviral therapy that minimizes hepatic complication risk is essential in optimizing HIV-HCV treatment. Nucleoside-sparing boosted protease inhibitor monotherapy may achieve this goal. METHODS: A prospective, open-label pilot simplification study of once-daily lopinavir/ritonavir (LPV/r) monotherapy in HIV-HCV coinfected patients was conducted in patients on HAART with undetectable HIV RNA for ≥6 months. The primary outcome was maintenance of HIV RNA<50 copies/mL through week 48. HIV RNA, immune measures, metabolic markers, and pharmacokinetics were assessed. RESULTS: Twenty participants received once-daily LPV/r monotherapy. Mean baseline age was 46.9 years and CD4 467 cells/L. By per protocol analysis, 71.4% (95% CI, 45.4-88.3) remained on once-daily LPV/r monotherapy with virologic suppression at week 48. Virologic breakthrough (HIV RNA>50 copies/mL on 2 consecutive measures) occurred in 7 patients (mean standard error [SE] time to breakthrough, 38.3 [4.8] weeks). Resuppression occurred with improved adherence in 2 participants and improved adherence plus addition of nucleosides in 2 others. LPV C min was <1 mg/L in 8 patients and was associated with virologic breakthrough in 2 cases but with no development of resistance. No clinically significant changes in CD4, lipids, or glucose were noted. Three participants developed transient≥5-fold liver enzyme elevations. None of 9 severe adverse events were LPV/r- or liver-related. Six discontinued participation for withdrawal of consent (n=1), poor adherence (n=3), or drug intolerance (n=2). CONCLUSIONS: Once-daily LPV/r monotherapy in HIV-HCV coinfected individuals offers a safe and effective approach to the management of the HIV infection, with a predictable pharmacokinetic profile.

Pilot, randomized study assessing safety, tolerability and efficacy of simplified LPV/r maintenance therapy in HIV patients on the 1 PI-based regimen.

OBJECTIVES: To compare the efficacy and safety of an individualized treatment-simplification strategy consisting of switching from a highly-active anti-retroviral treatment (HAART) with a ritonavir-boosted protease inhibitor (PI/r) and 2 nucleoside reverse-transcriptase inhibitors (NRTIs) to lopinavir/ritonavir (LPV/r) monotherapy, with intensification by 2 NRTIs if necessary, to that of continuing their HAART. METHODS: This is a one-year, randomized, open-label, multi-center study in virologically-suppressed HIV-1-infected adults on their first PI/r-containing treatment, randomized to either LPV/r-monotherapy or continue their current treatment. Treatment efficacy was determined by plasma HIV-1 RNA viral load (VL), time-to-virologic rebound, patient-reported outcomes (PROs) and CD4+T-cell-count changes. Safety was assessed with the incidence of treatment-emergent adverse events (AE). RESULTS: Forty-one patients were randomized to LPV/r and 39 to continue their HAART. No statistically-significant differences between the two study groups in demographics and baseline characteristics were observed. At day-360, 71(39:LPV/r;32:HAART) patients completed treatment, while 9(2:LPV/r;7:HAART) discontinued. In a Last Observation Carried Forward Intent-to-Treat analysis, 40(98%) patients on LPV/r and 37(95%) on HAART had VL<200 copies/mL (P = 0.61). Time-to-virologic rebound, changes in PROs, CD4+ T-cell-count and VL from baseline, also exhibited no statistically-significant between-group differences. Most frequent AEs were diarrhea (19%), headache (18%) and influenza (16%). Four (10%) patients on LPV/r were intensified with 2 NRTIs, all regaining virologic control. Eight serious AEs were reported by 5(2:LPV/r;3:HAART) patients. CONCLUSION: At day-360, virologic efficacy and safety of LPV/r appears comparable to that of a PI+2NRTIs HAART. These results suggest that our individualized, simplified maintenance strategy with LPV/r-monotherapy and protocol-mandated NRTI re-introduction upon viral rebound, in virologically-suppressed patients merits further prospective long-term evaluation. TRIAL REGISTRATION: ClinicalTrials.gov NCT00159224.

Effectiveness and tolerability of oral administration of low-dose salmon oil to HIV patients with HAART-associated dyslipidemia.

PURPOSE: To assess the effectiveness of low-dose salmon oil for the treatment of highly active antiretroviral therapy (HAART)-induced dyslipidemia in HIV-infected patients. METHOD: Randomized, open-label, parallel and crossover, multicenter study. Patients received 1 g salmon oil tid for 24 weeks (SO-24) or no additional treatment for 12 weeks and salmon oil for weeks 12 to 24 (CT-SO). The primary outcome measure was the change in triglyceride (TG) levels. RESULTS: Fifty-eight patients completed the study (26 in SO-24; 32 in CT-SO). After 12 weeks, the SO-24 group experienced a mean TG reduction of 1.1 mmol/L, compared to an increase of 0.3 mmol/L for the CT-SO group (p = .040). When CT-SO patients were crossed over to salmon oil treatment, mean TG decreased by 0.7 mmol/L (p = .052). Concomitant use of fibrates, statins, or both were reported by 16 (27.6%), 10 (17.2%), and 8 (13.8%), respectively. Multivariate analysis showed that salmon oil produced a significant decrease in TG levels independent of other lipid-lowering medications (p = .022). There were 26 predominately mild treatment-emergent (antiretroviral or salmon oil) nonserious adverse events reported by 22 (33.3%) patients. CONCLUSION: Low-dose salmon oil (3 g/day) is effective and well-tolerated in reducing TG levels in HIV-infected patients receiving HAART.

Randomized controlled trial of once-daily tenofovir, lamivudine, and lopinavir/ritonavir versus remaining on the same regimen in virologically suppressed HIV-infected patients on their first PI-containing HAART regimen.

PURPOSE: To assess the effects of switching to once-daily (QD) lopinavir/ritonavir (LPV/r)-based combination therapy in HIV-infected patients who are virologically suppressed (HIV viral load <50 copies/mL) on their first protease inhibitor (PI)-containing regimen. METHOD: In this 48-week, prospective, open-label, randomized study, patients were either switched to once-daily LPV/r, tenofovir (TDF), and lamivudine (3TC) (QD arm) or remained on their existing regimen (control arm). The primary endpoint of the study was the proportion of patients maintaining virologic suppression following 48 weeks of treatment. RESULTS: Fifty and 22 patients were randomized to the QD and control arms, respectively. At week 48, there was no significant difference in virological suppression between the QD and control arms using intent-to-treat (missing = failure) analysis (p = .44). There was no significant difference in discontinuation rates between the two arms (p = .66). Significantly more patients randomized to the QD arm reported gastrointestinal adverse events compared with the control arm (p = .009). There were no study drug-related serious adverse events. CONCLUSION: For patients who are already virologically suppressed on their first PI-containing regimen, switching to a QD regimen of TDF+3TC+LPV/r resulted in similar rates of virologic suppression when compared with staying on existing therapy.