TY - JOUR
T1 - Nucleoside reverse transcriptase inhibitor resistance mutations associated with first-line stavudine-containing antiretroviral therapy
T2 - Programmatic implications for countries phasing out stavudine
AU - Tang, Michele W.
AU - Rhee, Soo Yon
AU - Bertagnolio, Silvia
AU - Ford, Nathan
AU - Holmes, Susan
AU - Sigaloff, Kim C.
AU - Hamers, Raph L.
AU - De Wit, Tobias F.Rinke
AU - Fleury, Herve J.
AU - Kanki, Phyllis J.
AU - Ruxrungtham, Kiat
AU - Hawkins, Claudia A.
AU - Wallis, Carole L.
AU - Stevens, Wendy
AU - Van Zyl, Gert U.
AU - Manosuthi, Weerawat
AU - Hosseinipour, Mina C.
AU - Ngo-Giang-Huong, Nicole
AU - Belec, Laurent
AU - Peeters, Martine
AU - Aghokeng, Avelin
AU - Bunupuradah, Torsak
AU - Burda, Sherri
AU - Cane, Patricia
AU - Cappelli, Giulia
AU - Charpentier, Charlotte
AU - Dagnra, Anoumou Y.
AU - Deshpande, Alaka K.
AU - El-Katib, Ziad
AU - Eshleman, Susan H.
AU - Fokam, Joseph
AU - Gody, Jean Chrysostome
AU - Katzenstein, David
AU - Koyalta, Donato D.
AU - Kumwenda, Johnstone J.
AU - Lallemant, Marc
AU - Lynen, Lutgarde
AU - Marconi, Vincent C.
AU - Margot, Nicolas A.
AU - Moussa, Sandrine
AU - Ndung'U, Thumbi
AU - Nyambi, Phillipe N.
AU - Orrell, Catherine
AU - Schapiro, Jonathan M.
AU - Schuurman, Rob
AU - Sirivichayakul, Sunee
AU - Smith, Davey
AU - Zolfo, Maria
AU - Jordan, Michael R.
AU - Shafer, Robert W.
PY - 2013/6/15
Y1 - 2013/6/15
N2 - Background The World Health Organization Antiretroviral Treatment Guidelines recommend phasing-out stavudine because of its risk of long-term toxicity. There are two mutational pathways of stavudine resistance with different implications for zidovudine and tenofovir cross-resistance, the primary candidates for replacing stavudine. However, because resistance testing is rarely available in resource-limited settings, it is critical to identify the cross-resistance patterns associated with first-line stavudine failure.MethodsWe analyzed HIV-1 resistance mutations following first-line stavudine failure from 35 publications comprising 1,825 individuals. We also assessed the influence of concomitant nevirapine vs. efavirenz, therapy duration, and HIV-1 subtype on the proportions of mutations associated with zidovudine vs. tenofovir cross-resistance.ResultsMutations with preferential zidovudine activity, K65R or K70E, occurred in 5.3% of individuals. Mutations with preferential tenofovir activity, ≥two thymidine analog mutations (TAMs) or Q151M, occurred in 22% of individuals. Nevirapine increased the risk of TAMs, K65R, and Q151M. Longer therapy increased the risk of TAMs and Q151M but not K65R. Subtype C and CRF01-AE increased the risk of K65R, but only CRF01-AE increased the risk of K65R without Q151M.ConclusionsRegardless of concomitant nevirapine vs. efavirenz, therapy duration, or subtype, tenofovir was more likely than zidovudine to retain antiviral activity following first-line d4T therapy.
AB - Background The World Health Organization Antiretroviral Treatment Guidelines recommend phasing-out stavudine because of its risk of long-term toxicity. There are two mutational pathways of stavudine resistance with different implications for zidovudine and tenofovir cross-resistance, the primary candidates for replacing stavudine. However, because resistance testing is rarely available in resource-limited settings, it is critical to identify the cross-resistance patterns associated with first-line stavudine failure.MethodsWe analyzed HIV-1 resistance mutations following first-line stavudine failure from 35 publications comprising 1,825 individuals. We also assessed the influence of concomitant nevirapine vs. efavirenz, therapy duration, and HIV-1 subtype on the proportions of mutations associated with zidovudine vs. tenofovir cross-resistance.ResultsMutations with preferential zidovudine activity, K65R or K70E, occurred in 5.3% of individuals. Mutations with preferential tenofovir activity, ≥two thymidine analog mutations (TAMs) or Q151M, occurred in 22% of individuals. Nevirapine increased the risk of TAMs, K65R, and Q151M. Longer therapy increased the risk of TAMs and Q151M but not K65R. Subtype C and CRF01-AE increased the risk of K65R, but only CRF01-AE increased the risk of K65R without Q151M.ConclusionsRegardless of concomitant nevirapine vs. efavirenz, therapy duration, or subtype, tenofovir was more likely than zidovudine to retain antiviral activity following first-line d4T therapy.
KW - AZT
KW - HIV-1
KW - NRTI
KW - TDF
KW - d4T
KW - drug resistance
KW - mutations
KW - nucleoside reverse transcriptase inhibitor
KW - stavudine
KW - subtypes
KW - tenofovir
KW - zidovudine
UR - http://www.scopus.com/inward/record.url?scp=84878329003&partnerID=8YFLogxK
U2 - https://doi.org/10.1093/infdis/jit114
DO - https://doi.org/10.1093/infdis/jit114
M3 - Article
C2 - 23687292
SN - 0022-1899
VL - 207
SP - S70-S77
JO - Journal of infectious diseases
JF - Journal of infectious diseases
IS - SUPPL.2
ER -