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Objectives PIANO (Paediatric study of Intelence As an NNRTI Option; TMC125-C213; NCT00665847) assessed the safety/tolerability, antiviral activity and pharmacokinetics of etravirine plus an optimized background regimen (OBR) in treatment-experienced, HIV-1-infected children (≥ 6 to 95% adherent by questionnaire and 39% by pill count. Forty-one patients experienced virological failure (VF; time-to-loss-of-virological-response non-VF-censored algorithm) (29 nonresponders; 12 rebounders). Of 30 patients with VF with paired baseline/endpoint genotypes, 18 (60%) developed nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations, most commonly Y181C. Mean etravirine area under the plasma concentration–time curve over 12 h (AUC0–12h; 5216 ng h/mL) and C0h (346 ng/mL) were comparable to adult target values. Conclusions Results with etravirine 5.2 mg/kg bid (with OBR) in this treatment-experienced paediatric population and etravirine 200 mg bid in treatment-experienced adults were comparable. Etravirine is an NNRTI option for treatment-experienced paediatric patients.

Background ODIN (once-daily darunavir in treatment-experienced patients) was a 48-week, phase III, randomized, open-label trial comparing once-daily (qd) darunavir/ritonavir (DRV/r) 800/100 mg with twice-daily (bid) DRV/r 600/100 mg, both with an optimized background regimen [OBR; at least two nucleoside reverse transcriptase inhibitors (NRTIs)], in treatment-experienced, HIV-1-infected adults with no DRV resistance-associated mutations (RAMs) at screening. Week 48 analyses of virological response by subgroups are reported. Methods A total of 590 patients were randomized to receive qd (n = 294) or bid (n = 296) DRV/r. Virological response (HIV-1 RNA 50 000 copies/mL. Response rates for the qd and bid treatment arms by baseline CD4 cell count were also similar (69.6 vs. 65.2% for

Objective This paper presents the final analysis of once-daily darunavir/ritonavir (DRV/r) vs. lopinavir/ritonavir (LPV/r) in treatment-naive HIV-1-infected adults. Methods ARTEMIS (AntiRetroviral Therapy with TMC114 ExaMined In naive Subjects; NCT00258557) was a randomized, open-label, phase-III, 192-week trial. Patients were stratified by baseline HIV-1 RNA and CD4 count, and randomized to once-daily DRV/r 800/100 mg or LPV/r 800/200 mg total daily dose (either once or twice daily) plus tenofovir/emtricitabine. Results Of 689 randomized patients receiving treatment (DRV/r: 343; LPV/r: 346), 85 and 114 patients in the DRV/r and LPV/r arms, respectively, had discontinued by week 192. Noninferiority was shown in the primary endpoint of virological response (HIV-1 RNA Conclusion Over 192 weeks, once-daily DRV/r was noninferior and statistically superior in virological response to LPV/r, with a more favourable gastrointestinal profile, demonstrating its suitability for long-term use in treatment-naive patients.

Tibotec BVBA, Mechelen, BelgiumBackgroundDarunavir (TMC114) is a new HIV protease inhibitor (PI).DesignThis Phase I, randomized, open-label trial compared the effects of darunavir plus low-dose ritonavir(RTV) (darunavir/RTV) with those of atazanavir/RTV on lipid and glucose parameters.MethodsForty-nine HIV-negative, healthy male volunteers received RTV 100mg once a day (qd) for 7 days,followed by either darunavir/RTV 800/100mg qd (n525) or atazanavir/RTV 300/100mg qd (n524)for 21 days. Mean changes in fasting lipid and glucose parameters at day 28 were calculated usingpost-RTV alone (day 7) and baseline (day 1) values as references. Short-term safety, tolerabilityand RTV pharmacokinetic parameters were evaluated.ResultsAfter 7 days of RTV treatment, the mean triglyceride concentration increased by approximately30mg/dL in both groups, changes in other lipid and glucose parameters were relatively small. Meanconcentrations of lipids and glucose over the treatment period were mostly similar between thetreatment groups. Mean changes from day 7 to day 28 for the darunavir/RTV and atazanavir/RTVgroups, respectively, were 3.6 and 0.5mg/dL for high-density lipoprotein cholesterol; 5.0 and5.3mg/dL for low-density lipoprotein cholesterol; 4.9 and 1.2 mg/dL for total cholesterol; 6.4 and14.0 mg/dL for triglycerides; 1.7 and 2.4mg/dL for glucose; and 1.4 and 0.3mg/dL forinsulin. No grade 3 or 4 lipid or glucose laboratory abnormalities were reported. Treatment-emergent hyperbilirubinaemia was reported for all volunteers (including five grade 4 cases) duringatazanavir/RTV treatment.ConclusionsCo-administration of darunavir or atazanavir with low-dose RTV resulted in minor and similarchanges in lipid and glucose parameters in HIV-negative healthy volunteers.Keywords: atazanavir, darunavir, HIV, lipids, metabolic, protease inhibitors, TMC114Accepted 20 November 2008