Title: Global epidemiology of drug resistance after failure of WHO recommended first-line regimens for adult HIV-1 infection: a multicentre retrospective cohort study
Authors: The TenoRes Study Group* Gregson J, Tang M, Ndembi N, Hamers RL, ..., de Oliveira T, ..., Shafer RW, Gupta KR.
Journal: Lancet Infect Dis.,15:http://dx.doi.org/10.1016/S1473-3099(15)00536-8 (2016)
Journal Impact Factor (I.F.): 16.144
Number of citations (Google Scholar): 20
Background Antiretroviral therapy (ART) is crucial for controlling HIV-1 infection through wide-scale treatment as
prevention and pre-exposure prophylaxis (PrEP). Potent tenofovir disoproxil fumarate-containing regimens are
increasingly used to treat and prevent HIV, although few data exist for frequency and risk factors of acquired drug
resistance in regions hardest hit by the HIV pandemic. We aimed to do a global assessment of drug resistance after
virological failure with first-line tenofovir-containing ART.
Methods The TenoRes collaboration comprises adult HIV treatment cohorts and clinical trials of HIV drug resistance
testing in Europe, Latin and North America, sub-Saharan Africa, and Asia. We extracted and harmonised data for
patients undergoing genotypic resistance testing after virological failure with a first-line regimen containing tenofovir
plus a cytosine analogue (lamivudine or emtricitabine) plus a non-nucleotide reverse-transcriptase inhibitor (NNRTI;
efavirenz or nevirapine). We used an individual participant-level meta-analysis and multiple logistic regression to
identify covariates associated with drug resistance. Our primary outcome was tenofovir resistance, defi ned as presence
of K65R/N or K70E/G/Q mutations in the reverse transcriptase (RT) gene.
Findings We included 1926 patients from 36 countries with treatment failure between 1998 and 2015. Prevalence of
tenofovir resistance was highest in sub-Saharan Africa (370/654 [57%]). Pre-ART CD4 cell count was the covariate
most strongly associated with the development of tenofovir resistance (odds ratio [OR] 1.50, 95% CI 1.27-1.77 for
CD4 cell count <100 cells per ?L). Use of lamivudine versus emtricitabine increased the risk of tenofovir resistance
across regions (OR 1.48, 95% CI 1.20-1.82). Of 700 individuals with tenofovir resistance, 578 (83%) had cytosine
analogue resistance (M184V/I mutation), 543 (78%) had major NNRTI resistance, and 457 (65%) had both. The mean
plasma viral load at virological failure was similar in individuals with and without tenofovir resistance (145 700 copies
per mL [SE 12 480] versus 133 900 copies per mL [SE 16 650; p=0.626]).
Interpretation We recorded drug resistance in a high proportion of patients after virological failure on a tenofovircontaining first-line regimen across low-income and middle-income regions. Effective surveillance for transmission
of drug resistance is crucial.
Citation: The TenoRes Study Group* Gregson J, Tang M, Ndembi N, Hamers RL, ..., de Oliveira T, ..., Shafer RW, Gupta KR. Global epidemiology of drug resistance after failure of WHO recommended first-line regimens for adult HIV-1 infection: a multicentre retrospective cohort study Lancet Infect Dis.,15:http://dx.doi.org/10.1016/S1473-3099(15)00536-8 (2016).