HIV-2 Infection, End-Stage Renal Disease and Protease Inhibitor Intolerance

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 treatment-experienced 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.

In VitroAntiviral Activity of Cabotegravir against HIV-2

“…HIV-2 is susceptible to the INIs raltegravir, elvitegravir, and dolutegravir, with 50% effective concentrations (EC 50 s) in the low-nanomolar to picomolar range (26)(27)(28)(29)(30)(31). Data from case studies and small case series indicate that raltegravir-and elvitegravir-based regimens can suppress HIV-2 viral loads in ART-naive individuals (32,33) and in ART-experienced patients whose treatment history does not include an INI (32,(34)(35)(36)(37)(38)(39). More recently, two groups conducting clinical trials in ART-naive HIV-2-infected patients reported favorable immunovirologic outcomes in response to INI-based regimens (40,41).…”

HIV-2: Testing Specificities

“…Integrase inhibitors are active on HIV-2; several in vitro studies on patient isolates and case series showed good activity Damond et al 2008a): raltegravir is therefore an option in case of failure or intolerability to other drugs (Francisci et al 2011), but long-term data are lacking at this point . No randomized clinical trials were performed to investigate response to treatment in HIV-2 patients (Gottlieb et al 2008a).…”