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Updated: Jun 21, 2026

Rapid Screening of HIV Reverse Transcriptase and Integrase Inhibitors
Published on: April 9, 2014
Mutation N155H in HIV-2 integrase confers high phenotypic resistance to raltegravir and impairs replication capacity
María Salgado1, Carlos Toro, Ainhoa Simón
1Service of Infectious Diseases, Hospital Carlos III, Madrid, Spain.
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.
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