HIV-2 Infection, End-Stage Renal Disease and Protease Inhibitor Intolerance
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CASE REPORT
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HIV-2 Infection, End-Stage Renal Disease and Protease Inhibitor Intolerance Which Salvage Regimen? Daniela Francisci,1 Laura Martinelli,1 Liliana E. Weimer,2 Maurizio Zazzi,3 Marco Floridia,2 Giulia Masini1 and Franco Baldelli1 1 Clinic of Infectious Diseases, Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy 2 Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanita`, Rome, Italy 3 Department of Molecular Biology, Section of Microbiology, University of Siena, Siena, Italy
Abstract
Non-nucleoside reverse transcriptase inhibitors and enfuvirtide are ineffective against HIV-2 replication. These considerations may have particular significance in the formulation of second-line or salvage regimens for HIV-2 infection when resistance or toxicity precludes the use of protease inhibitors (PIs) or specific nucleoside analogues. We describe a case of a treatmentexperienced patient with important limitations in therapeutic options dictated by the presence of HIV-2 infection, severe HIV nephropathy (requiring haemodialysis), intolerance to PIs and clinical contraindications to the use of some nucleoside analogues (anaemia, pancreatic toxicity and high cardiovascular risk). A three-drug regimen based on raltegravir, tenofovir disoproxil fumarate and lamivudine was given, with no major toxicity, good immunological response and complete viral suppression. Our case indicates that regimens based on integrase inhibitors could represent an effective alternative in PI-resistant or PI-intolerant patients with HIV-2, and that tenofovir disoproxil fumarate may be used in patients with end-stage renal disease requiring haemodialysis who cannot take other nucleoside analogues because of treatment-limiting adverse effects.
1. Introduction The distinct genetic characteristics of HIV-1 and HIV-2 translate into significant differences in drug susceptibility and therapeutic options. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) and enfuvirtide are ineffective against HIV-2, and a reduced activity of some protease inhibitors (PIs) has also been described as a consequence of the weaker affinity binding of PIs against HIV-2 protease compared with HIV-1.[1-5] These constraints may be particularly limiting in
the formulation of second-line and salvage regimens in this context, and the introduction of new classes of antiretroviral drugs is therefore highly relevant in this setting. Raltegravir was the first HIV integrase inhibitor to be approved by regulatory agencies, and it has been shown to be effective in reducing viral load and increasing CD4+ counts in both treatment-experienced and treatment-naı¨ ve HIV-1-infected patients.[6,7] The drug is active against HIV-2 and may therefore represent an important resource for patients with HIV-2 who have few alternative options left
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because of toxicity or treatment failure.[8,9] We describe here the use of a three-dru
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