Novel Antiretroviral Combinations in Treatment-Experienced Patients with HIV Infection: Rationale and Results

摘要: Novel antiretroviral drugs offer different degrees of improvement in activity against drug-resistant HIV, short- and long-term tolerability, dosing convenience compared with earlier drugs. Those approved more recently commonly used treatment-experienced patients include the entry inhibitor enfuvirtide, protease inhibitors (PIs) [darunavir tipranavir], a C-C chemokine receptor (CCR) type 5 antagonist (maraviroc), an integrase (raltegravir) etravirine, non-nucleoside reverse transcriptase (NNRTI). agents stages development CCR5 monoclonal antibody (PRO 140) administered subcutaneously once weekly, once-daily (elvitegravir S/GSK1349572), several nucleoside (nucleotide) NNRTIs. Bevirimat, maturation inhibitor, has compromised presence relatively common Gag polymorphisms. Viral suppression is necessary to control evolution drug resistance, reduce chronic immune activation that probably underlies excess morbidity mortality HIV-infected patients, viral transmission, including transmitted resistance. In general, proportion viraemic who achieve increases number active pharmacokinetically compatible regimen. ANRS139-TRIO trial, 86% highly treated darunavir-ritonavir, etravirine raltegravir had HIV RNA <50 copies/mL at 48 weeks. received least 12 weeks stable regimen no darunavir resistance-associated mutations, boosted ritonavir 100 mg was virologically noninferior better lipid effects than twice-daily dosing, which requires 200 total daily dose ritonavir. Raltegravir plus PI being investigated for second-line therapy not responding NNRTI-based first-line treatment resource-limited settings (RLS). However, concerns about this potential strategy low barrier resistance raltegravir, limited penetration some PIs into CNS unknown impact polymorphisms seen non-B subtype HIV-1. have already achieved suppression, novel may be simplify schedule, lower costs (such as by switching monotherapy), adverse events or preserve options, especially since absence eradication implies need life-long combination therapy. Switching enfuvirtide eliminated painful injection-site reactions without compromising virological suppression. Two studies found outcomes when were switched from lopinavir/ritonavir but there profile. Simplifying darunavir-ritonavir monotherapy after plasma been safe emergence cases rebound, longer-term data are needed. The initial suggestion maraviroc possess unique CD4+ T-cell boosting confirmed clinical trials. Improved understanding pathogenesis opened new frontiers research such identifying sources, consequences optimal management residual viraemia those copies/mL. Globally, however, one most urgent priorities providing increasing failing RLS access treatment, treatments based on agents.