Mutational Correlates of Virological Failure in Individuals Receiving a WHO-Recommended Tenofovir-Containing First-Line Regimen: An International Collaboration

作者：Rhee Soo Yon^*; Varghese Vici; Holmes Susan P; Van Zyl Gert U; Steegen Kim; Boyd Mark A; Cooper David A; Nsanzimana Sabin; Saravanan Shanmugam; Charpentier Charlotte; de Oliveira Tulio; Etiebet Mary Ann A; Garcia Federico; Goedhals Dominique; Gomes Perpetua; Gunthard Huldrych F; Hamers Raph L; Hoffmann Christopher J; Hunt Gillian; Jiamsakul Awachana; Kaleebu Pontiano; Kanki Phyllis; Kantor Rami; Kerschberger Bernhard; Marconi Vincent C; Ndahimana Jean D'amour

来源：EBioMedicine, 2017, 18: 225-235.

DOI：10.1016/j.ebiom.2017.03.024

• HIV-1
• Antiretroviral therapy
• Reverse transcriptase
• Drug resistance
• Tenofovir
• WHO-recommended first-line

Tenofovir disoproxil fumarate (TDF) genotypic resistance defined by K65R/N and/ or K70E/Q/G occurs in 20% to 60% of individuals with virological failure (VF) on aWHO-recommended TDF-containing first-line regimen. However, the full spectrumof reverse transcriptase (RT) mutations selected in individuals with VF on such a regimen is not known. To identify TDF regimen-associated mutations (TRAMs), we compared the proportion of each RT mutation in 2873 individuals with VF on a WHO-recommended first-line TDF-containing regimen to its proportion in a cohort of 50,803 antiretroviral-naive individuals. To identify TRAMs specifically associatedwith TDF-selection pressure, we compared the proportion of each TRAMto its proportion in a cohort of 5805 individuals with VF on a first-line thymidine analog-containing regimen. We identified 83 TRAMs including 33 NRTI-associated, 40 NNRTI-associated, and 10 uncommon mutations of uncertain provenance. Of the 33 NRTI-associated TRAMs, 12-A62V, K65R/N, S68G/N/D, K70E/Q/T, L74I, V75L, and Y115F -weremore common among individuals receiving a first-line TDF-containing compared to a first-line thymidine analog-containing regimen. These 12 TDF-selected TRAMswill be important formonitoring TDF-associated transmitted drug-resistance and for determining the extent of reduced TDF susceptibility in individuals with VF on a TDF-containing regimen.

• 出版日期2017-4
• 单位河北医科大学