@article{fdi:010064657,
  title = {{G}eographic and temporal trends in the molecular epidemiology and genetic mechanisms of transmitted {HIV}-1 drug resistance : an individual-patient- and sequence-level meta-analysis},
  author = {{R}hee, {S}. {Y}. and {B}lanco, {J}. {L}. and {J}ordan, {M}. {R}. and {T}aylor, {J}. and {L}emey, {P}. and {V}arghese, {V}. and {H}amers, {R}. {L}. and {B}ertagnolio, {S}. and de {W}it, {T}. {R}. and {A}ghokeng {F}obang, {A}velin and {A}lbert, {J}. and {A}vi, {R}. and {A}vila-{R}ios, {S}. and {B}essong, {P}. {O}. and {B}rooks, {J}. {I}. and {B}oucher, {C}. {A}. {B}. and {B}rumme, {Z}. {L}. and {B}usch, {M}. {P}. and {B}ussmann, {H}. and {C}haix, {M}. {L}. and {C}hin, {B}. {S}. and {D}'{A}quin, {T}. {T}. and {D}e {G}ascun, {C}. {F}. and {D}erache, {A}. and {D}escamps, {D}. and {D}eshpande, {A}. {K}. and {D}joko, {C}. {F}. and {E}shleman, {S}. {H}. and {F}leury, {H}. and {F}range, {P}. and {F}ujisaki, {S}. and {H}arrigan, {P}. {R}. and {H}attori, {J}. and {H}olguin, {A}. and {H}unt, {G}. {M}. and {I}chimura, {H}. and {K}aleebu, {P}. and {K}atzenstein, {D}. and {K}iertiburanakul, {S}. and {K}im, {J}. {H}. and {K}im, {S}. {S}. and {L}i, {Y}. {P}. and {L}utsar, {I}. and {M}orris, {L}. and {N}dembi, {N}. and {P}eng, {N}. {G}. {K}. and {P}aranjape, {R}. {S}. and {P}eeters, {M}artine and {P}oljak, {M}. and {P}rice, {M}. {A}. and {R}agonnet-{C}ronin, {M}. {L}. and {R}eyes-{T}eran, {G}. and {R}olland, {M}. and {S}irivichayakul, {S}. and {S}mith, {D}. {M}. and {S}oares, {M}. {A}. and {S}oriano, {V}. {V}. and {S}semwanga, {D}. and {S}tanojevic, {M}. and {S}tefani, {M}. {A}. and {S}ugiura, {W}. and {S}ungkanuparph, {S}. and {T}anuri, {A}. and {T}ee, {K}. {K}. and {T}ruong, {H}. {H}. {M}. and van de {V}ijver, {D}amc and {V}idal, {N}icole and {Y}ang, {C}. {F}. and {Y}ang, {R}. {G}. and {Y}ebra, {G}. and {I}oannidis, {J}. {P}. {A}. and {V}andamme, {A}. {M}. and {S}hafer, {R}. {W}.},
  editor = {},
  language = {{ENG}},
  abstract = {{B}ackground {R}egional and subtype-specific mutational patterns of {HIV}-1 transmitted drug resistance ({TDR}) are essential for informing first-line antiretroviral ({ARV}) therapy guidelines and designing diagnostic assays for use in regions where standard genotypic resistance testing is not affordable. {W}e sought to understand the molecular epidemiology of {TDR} and to identify the {HIV}-1 drug-resistance mutations responsible for {TDR} in different regions and virus subtypes. {M}ethods and {F}indings {W}e reviewed all {G}en{B}ank submissions of {HIV}-1 reverse transcriptase sequences with or without protease and identified 287 studies published between {M}arch 1, 2000, and {D}ecember 31, 2013, with more than 25 recently or chronically infected {ARV}-naive individuals. {T}hese studies comprised 50,870 individuals from 111 countries. {E}ach set of study sequences was analyzed for phylogenetic clustering and the presence of 93 surveillance drug-resistance mutations ({SDRM}s). {T}he median overall {TDR} prevalence in sub-{S}aharan {A}frica ({SSA}), south/southeast {A}sia ({SSEA}), upper-income {A}sian countries, {L}atin {A}merica/{C}aribbean, {E}urope, and {N}orth {A}merica was 2.8%, 2.9%, 5.6%, 7.6%, 9.4%, and 11.5%, respectively. {I}n {SSA}, there was a yearly 1.09-fold (95% {CI}: 1.05-1.14) increase in odds of {TDR} since national {ARV} scale-up attributable to an increase in non-nucleoside reverse transcriptase inhibitor ({NNRTI}) resistance. {T}he odds of {NNRTI}-associated {TDR} also increased in {L}atin {A}merica/{C}aribbean (odds ratio [{OR}] = 1.16; 95% {CI}: 1.06-1.25), {N}orth {A}merica ({OR} = 1.19; 95% {CI}: 1.12-1.26), {E}urope ({OR} = 1.07; 95% {CI}: 1.01-1.13), and upper-income {A}sian countries ({OR} = 1.33; 95% {CI}: 1.12-1.55). {I}n {SSEA}, there was no significant change in the odds of {TDR} since national {ARV} scale-up ({OR} = 0.97; 95% {CI}: 0.92-1.02). {A}n analysis limited to sequences with mixtures at less than 0.5% of their nucleotide positions-a proxy for recent infection-yielded trends comparable to those obtained using the complete dataset. {F}our {NNRTI} {SDRM}s-{K}101{E}, {K}103{N}, {Y}181{C}, and {G}190{A}-accounted for > 80% of {NNRTI}-associated {TDR} in all regions and subtypes. {S}ixteen nucleoside reverse transcriptase inhibitor ({NRTI}) {SDRM}s accounted for > 69% of {NRTI}-associated {TDR} in all regions and subtypes. {I}n {SSA} and {SSEA}, 89% of {NNRTI} {SDRM}s were associated with high-level resistance to nevirapine or efavirenz, whereas only 27% of {NRTI} {SDRM}s were associated with high-level resistance to zidovudine, lamivudine, tenofovir, or abacavir. {O}f 763 viruses with {TDR} in {SSA} and {SSEA}, 725 (95%) were genetically dissimilar; 38 (5%) formed 19 sequence pairs. {I}nherent limitations of this study are that some cohorts may not represent the broader regional population and that studies were heterogeneous with respect to duration of infection prior to sampling. {C}onclusions {M}ost {TDR} strains in {SSA} and {SSEA} arose independently, suggesting that {ARV} regimens with a high genetic barrier to resistance combined with improved patient adherence may mitigate {TDR} increases by reducing the generation of new {ARV}-resistant strains. {A} small number of {NNRTI}-resistance mutations were responsible for most cases of high-level resistance, suggesting that inexpensive point-mutation assays to detect these mutations may be useful for pre-therapy screening in regions with high levels of {TDR}. {I}n the context of a public health approach to {ARV} therapy, a reliable point-of-care genotypic resistance test could identify which patients should receive standard first-line therapy and which should receive a protease-inhibitor-containing regimen.},
  keywords = {{MONDE}},
  booktitle = {},
  journal = {{P}los {M}edicine},
  volume = {12},
  numero = {4},
  pages = {e1001810 [29 p.]},
  ISSN = {1549-1676},
  year = {2015},
  DOI = {10.1371/journal.pmed.1001810},
  URL = {https://www.documentation.ird.fr/hor/fdi:010064657},
}