BACKGROUND: Raltegravir has been shown to be active against wildtype HIV-2 with a phenotypic susceptibility similar to HIV-1. Due to the recent introduction of these novel inhibitors, information on the selection of resistance mutations and its phenotypic effect in this population is scarce. OBJECTIVES: To explore in vitro the effect of raltegravir resistance in one individual with HIV-2 infection who failed raltegravir-HAART. METHODS: A 20-year-old man with HIV-2 infection received a raltegravir-based HAART regimen. Drug resistance mutations were examined in the integrase gene by sequence analysis. Phenotypic analyses were performed in two HIV-2 isolates from the patient (wildtype isolate: SP-2p2-175 and mutant isolate: SP-2p2-189) and a laboratory reference strain (HIV-2 ROD). Susceptibility to raltegravir was assessed in a PBMC culture assay. Furthermore, a replicative capacity assay was performed. RESULTS: After introduction of raltegravir, patient's HIV-2 viremia dropped 1 log but did not reach undetectability. Genotypic analysis at month 8 with raltegravir, revealed the development of N155H resistant mutation along with other changes in the HIV-2 integrase: V72I, I84V, A153G, N160K and S163S/G. These changes resulted in a 37-fold increase in phenotypic resistance to raltegravir. Wildtype HIV-2 integrase (SP-2p2-175) had an IC(50) of 21.5nM and HIV-2 mutant virus (SP-2p2-189) showed an IC(50) of 789nM. SP-2p2-189 virus presented also lower replicative capacity in the absence of raltegravir than wildtype. CONCLUSION: A continued low HIV-2 viral load seems to be enough to select the N155H mutation, which despite significantly impairing viral replication, shows a level of resistance sufficient to give a selective advantage to the virus that maintains this pathway of resistance to raltegravir overtime.
BACKGROUND:Raltegravir has been shown to be active against wildtype HIV-2 with a phenotypic susceptibility similar to HIV-1. Due to the recent introduction of these novel inhibitors, information on the selection of resistance mutations and its phenotypic effect in this population is scarce. OBJECTIVES: To explore in vitro the effect of raltegravir resistance in one individual with HIV-2 infection who failed raltegravir-HAART. METHODS: A 20-year-old man with HIV-2 infection received a raltegravir-based HAART regimen. Drug resistance mutations were examined in the integrase gene by sequence analysis. Phenotypic analyses were performed in two HIV-2 isolates from the patient (wildtype isolate: SP-2p2-175 and mutant isolate: SP-2p2-189) and a laboratory reference strain (HIV-2 ROD). Susceptibility to raltegravir was assessed in a PBMC culture assay. Furthermore, a replicative capacity assay was performed. RESULTS: After introduction of raltegravir, patient's HIV-2 viremia dropped 1 log but did not reach undetectability. Genotypic analysis at month 8 with raltegravir, revealed the development of N155H resistant mutation along with other changes in the HIV-2 integrase: V72I, I84V, A153G, N160K and S163S/G. These changes resulted in a 37-fold increase in phenotypic resistance to raltegravir. Wildtype HIV-2 integrase (SP-2p2-175) had an IC(50) of 21.5nM and HIV-2 mutant virus (SP-2p2-189) showed an IC(50) of 789nM. SP-2p2-189 virus presented also lower replicative capacity in the absence of raltegravir than wildtype. CONCLUSION: A continued low HIV-2 viral load seems to be enough to select the N155H mutation, which despite significantly impairing viral replication, shows a level of resistance sufficient to give a selective advantage to the virus that maintains this pathway of resistance to raltegravir overtime.
Authors: Robert A Smith; Dana N Raugi; Vincent H Wu; Christopher G Zavala; Jennifer Song; Khardiata Mbaye Diallo; Moussa Seydi; Geoffrey S Gottlieb Journal: Antimicrob Agents Chemother Date: 2019-04-25 Impact factor: 5.191
Authors: Robert A Smith; Dana N Raugi; Vincent H Wu; Sally S Leong; Kate M Parker; Mariah K Oakes; Papa Salif Sow; Selly Ba; Moussa Seydi; Geoffrey S Gottlieb Journal: Antimicrob Agents Chemother Date: 2015-09-21 Impact factor: 5.191
Authors: Robert A Smith; Dana N Raugi; Nancy B Kiviat; Stephen E Hawes; James I Mullins; Papa S Sow; Geoffrey S Gottlieb Journal: AIDS Date: 2011-11-28 Impact factor: 4.177
Authors: Robert A Smith; Vincent H Wu; Christopher G Zavala; Dana N Raugi; Selly Ba; Moussa Seydi; Geoffrey S Gottlieb Journal: Antimicrob Agents Chemother Date: 2018-09-24 Impact factor: 5.191
Authors: Robert A Smith; Dana N Raugi; Charlotte Pan; Matthew Coyne; Alexandra Hernandez; Brad Church; Kara Parker; James I Mullins; Papa Salif Sow; Geoffrey S Gottlieb Journal: PLoS One Date: 2012-09-18 Impact factor: 3.240