Letter to the Editor: Successful Rescue Therapy with Raltegravir (MK-0518) and Etravirine (TMC125) in an HIV-Infected Patient Failing All Four Classes of Antiretroviral Drugs

Abstract

It is mandatory to find antiretroviral therapies that offer increased efficacy in treatmentexperienced patients with HIV-1 infection, a population whose extensive drug resistance restricts treatment options and has a severe effect on infection management.1 The aim in salvage therapy in patients who were highly treatmentexperienced and in whom multiple regimens had failed was so far limited to the new protease inhibitors (PI) and combination with enfuvirtide.2,3 The new antiretrovirals currently in expanded access programs, such as raltegravir and etravirine, show unprecedented level of virologic efficacy. Raltegravir, formerly MK0518, the first integrase inhibitor under clinical development, showed high potency in multidrug-resistant HIV patients including those resistant to currently available antiretroviral drugs.4 Etravirine, formerly TMC-125, a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) appears to be effective against a variety of HIV viruses that are resistant to efavirenz and nevirapine.5 Few data are available regarding the performance of these drugs combinations in heavily PI-experienced patients, including those for whom tipranavir, darunavir, and enfuvirtide have failed. Hereby, we describe the outcome of salvage therapy based on raltegravir and etravirine in a heavily antiretroviral-experienced patient. A 37-year-old Caucasian male, CDC status C3, had experienced multiple failures to all current classes of antiretroviral agents. Specifically, he had failed eight ritonavir-boosted PI combinations, including tenofovir-lamivudine-enfuvirtide-tipranavir/ritonavir, given in May 2004 with replacement of the latest with darunavir/ritonavir in December 2006. Plasma HIV-RNA levels were measured at baseline and during therapy using a commercial assay, the Versant HIV-1 RNA 3.0 Assay (bDNA; Siemens Medical Solutions Diagnostics, Malvern, PA), with a dynamic range of 50–500,000 HIV-1 RNA copies per milliliter. CD4 cell count was determined by direct immunofluorescence in flow cytometry (Beckman Coulter, Fullerton, CA). Genetic analysis of the pol gene including both HIV-1 reverse transcriptase (codons 4-99) and protease (codons 35-247) regions was performed using the Trugene HIV-1 Genotyping Kit (Siemens Medical Solutions Diagnostics).