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Objectives To compare virological effectiveness in patients who continued on a virologically successful first-line boosted protease inhibitor (PI)-containing combination antiretroviral therapy (cART) regimen or who switched to a PI-free cART including efavirenz, nevirapine or abacavir. Methods From the French Hospital Database on HIV, we selected 439 patients with undetectable viral load (VL) on a first-line boosted PI-containing cART regimen who switched to a PI-free combination including efavirenz, nevirapine or abacavir. Each of these patients was matched with three patients who continued to take their first-line cART regimen, on the basis of gender, age, CD4 cell count, VL, date of cART initiation and the duration of VL undetectability. Time to virological failure (VF) was analysed with Kaplan–Meier curves and Cox models. Results The 12 month probabilities of VF were 3.7% and 5.7% in non-switch and switch patients, respectively, and 3.9%, 7.2% and 9.0% in patients switching to efavirenz-, nevirapine- and abacavir-containing cART, respectively. After adjustment, only patients switching to abacavir-containing cART had a higher risk of VF than non-switch patients (adjusted hazard ratio, 1.99; 95% confidence interval, 1.05–3.79). Conclusions Switching from a virologically successful first-line boosted PI-containing cART regimen to a non-nucleoside reverse transcriptase inhibitor-containing cART regimen containing either efavirenz or nevirapine is virologically safe, while switching to abacavir-containing cART should be avoided. [ABSTRACT FROM PUBLISHER]

Abstract: Objective: This study was made to determine the immunovirological outcome and tolerance to lopinavir/ritonavir (LPV/r) in HIV-infected protease inhibitors-experienced patients with long-term virological failure. Design: Prospective follow-up was implemented for the French cohort ANRS CO8 Aproco-Copilote of 121 patients starting an LPV/r-containing regimen after a median duration of virological failure of 30.6 months. At baseline the median HIV-RNA plasma level was 4.1 log10 copies/ml and the median CD4 cell count was 273/mm3. Results: On initiation of LPV/r, these patients were heavily pre-treated: 62% had received at least 4 NRTI, 65% at least 1 NNRTI, and 33% at least 3 PI. On prescription of LPV/r, the associated antiretroviral regimen was: no drug to which patients were previously naïve in 49 cases (40%), at least one new drug in 72 cases: 1 NRTI (n =42), 2 NRTI (n =22), 1 NNRTI (n =10), at least one new PI (n =6), enfuvirtide (n =2). The median HIV-RNA level was 2 log10 copies/ml at M4 and M12, 1.7 log10 copies/ml at M24 with respectively 74, 71 and 85% of patients achieving plasma HIV-RNA below 2.7 log10 copies/ml. The median CD4 cell count was 385 and 429/mm3 at M12 and M24 respectively. Among patients with genotypic testing at the time of LPV/r initiation, Ninety-five percent had at the most 5 protease mutations known to reduce LPV/r susceptibility. Thirty serious adverse events were reported but only 6 were related to LPV/r. Conclusion: The use of LPV/r in HIV-infected patients failing multiple antiretroviral regimens provided a potent and durable immunovirological response. [Copyright &y& Elsevier]

Gastrointestinal intolerance is a limitation of boosted saquinavir antiretroviral treatment. We present three HIV-infected individuals whose severe toxicity symptoms started directly after initiation of a standard dose saquinavir hard-gel capsule-containing regimen (saquinavir/ritonavir 1000/100 mg). All patients underwent immediate 12 h pharmacokinetic (PK) assessment and showed extraordinarily high saquinavir plasma exposure. All three patients did not recover until the saquinavir exposure was decreased. This pilot case study anticipates a new concept of 'direct PK'-guided individual dose interventions under close viral load monitoring. Two major reasons for symptomatic saquinavir overexposure were defined: impaired liver function in a chronic hepatitis C virus co-infected individual at normal liver performance parameters and a delayed cytochrome p450 enzyme autoinduction. Overexposure seems to be an independent intolerance factor. Although delayed autoinduction is not well established as a reason for adverse events in saquinavir therapy, this observation may be confirmed in the near future by increased use. [ABSTRACT FROM AUTHOR]

Objective Nucleoside reverse transcriptase (NRTI) sparing is a favourable option for patients with NRTI failure or toxicity. Methods Patients judged to be failing NRTI therapy were enrolled in a single-arm, open-label study of indinavir/ritonavir (IDV/r) 800/100 mg twice a day (bid)+efavirenz (EFV) 600 mg once a day (qd). The primary endpoint was the change in time-weighted average HIV RNA from baseline. The initial 48-week protocol was extended to 96 weeks by a single amendment. Analysis was by intention to treat. Results Sixty-one patients (23 female) were enrolled in the study. Baseline median inter-quartile range (IQR) NRTI exposure was 4.4 (3.9–4.7) years; baseline median viral load was 4.09 log10 HIV-1 RNA copies/mL (range 3.75–4.61 log10 copies/mL); baseline median CD4 count was 169 cells/μL (range 60–277 cells/μL). The mean (SD) change in time-weighted average HIV RNA from baseline at 48 and 96 weeks was −2.1 (0.7) and −2.1 (0.8) log10 copies/mL respectively, resulting in 87% and 69% of patients with HIV RNA <50 copies/mL. Sixteen per cent of patients permanently ceased therapy and 26% underwent temporary drug interruptions because of study drug-related adverse events. Fasted-lipid values rose significantly over the 96 weeks of study, as did median blood glucose and median serum creatinine levels. Twelve (20%) patients underwent IDV dose reduction, mainly because of nephrotoxicity (nine of 12 patients). Blood pressure values deteriorated following switch, but markers of nucleoside toxicity improved. Conclusions IDV/r 800/100 mg bid+EFV 600 mg qd gave a potent, durable response in these NRTI failures and was reasonably well tolerated. However, we observed adverse effects on renal, metabolic and blood pressure parameters. Lower doses of boosted IDV might improve toxicity while maintaining efficacy, and this possibility warrants further investigation. [ABSTRACT FROM AUTHOR]

Presents a clinical trial on the efficacy and tolerability of a nucleoside reverse transcriptase inhibitor (NRTI)-sparing combination of lopinavir/ritonavir and efavirenz in HIV-positive persons. Class cross-resistance and mitochondrial toxicity are problems with antiretroviral regimens with NRTI; Mean viral load; CD4 count; Fasting lipid levels.