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• W2159933425 endingPage "3702" @default.
• W2159933425 startingPage "3696" @default.
• W2159933425 abstract "CD4(+) T cells and macrophages are the primary target cells for HIV in vivo, and antiretroviral drugs can vary in their ability to inhibit the infection of these different cell types. Resistance pathways to the HIV integrase inhibitor raltegravir have previously been investigated in T cells. Primary raltegravir resistance mutations, most often at integrase amino acid position 148 or 155, afford some resistance to the drug. The acquisition of pathway-specific secondary mutations then provides higher-level resistance to viruses infecting T cells. We show here that during macrophage infection, the presence of a single primary raltegravir resistance mutation (Q148H, Q148R, N155H, or N155S) is sufficient to provide resistance to raltegravir comparable to that seen in viruses expressing both primary and secondary mutations in costimulated CD4(+) T cells. These data implicate macrophages as a potential in vivo reservoir that may facilitate the development of resistance to raltegravir. Notably, the newer integrase inhibitor MK-2048 effectively suppressed the infection of all raltegravir-resistant viruses in both T cells and macrophages, indicating that more recently developed integrase inhibitors are capable of inhibiting infection in both major HIV cellular reservoirs, even in patients harboring raltegravir-resistant viruses." @default.
• W2159933425 created "2016-06-24" @default.
• W2159933425 creator A5051908366 @default.
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• W2159933425 date "2011-08-01" @default.
• W2159933425 modified "2023-10-15" @default.
• W2159933425 title "Single Mutations in HIV Integrase Confer High-Level Resistance to Raltegravir in Primary Human Macrophages" @default.
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• W2159933425 doi "https://doi.org/10.1128/aac.00566-11" @default.
• W2159933425 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3147632" @default.
• W2159933425 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21628534" @default.
• W2159933425 hasPublicationYear "2011" @default.
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