Stanford University HIV Drug Resistance Database - A curated public database designed to represent, store, and analyze the divergent forms of data underlying HIV drug resistance.

Antiretroviral drug summary: Didanosine (ddI; Videx)

Last updated on September 07, 2007
Key Mutations
L74V is the most common mutation occurring in patients receiving ddI monotherapy (Kozal et al. 1994; Shafer et al. 1994; St. Clair et al. 1991). It also occurs commonly in viruses from persons receiving ddI/3TC, ddI/FTC, or ddI/TDF. Although L74V reduces ddI susceptibility by only ~1.8 fold, it predicts a poor virologic response (Molina et al. 2005). L74I occurs less commonly than L74V, appearing more often in viruses containing multiple TAMs. Its phenotypic and clinical significance appears similar to that of L74V (Berkhout et al. 2006; Rhee et al. 2006).
K65R occurs in patients receiving ddI monotherapy (Winters et al. 1997), ddI/d4T, (Shafer et al. 2003), ddI/TDF, and ddI/TDF/3TC. It reduces ddI susceptibility ~2.0 fold. ddI is likely to be inactive at treating patients with viruses containing K65R. K65N is an rare mutation that has an effect on NRTI susceptibility similar to K65R (Margot et al. 2006; Ross et al. 2006).
TAMs are the primary mutations associated with virologic failure in patients receiving ddI/ZDV (Montaner et al. 1998; Shafer et al. 1995) and ddI/d4T (Coakley et al. 2000; Pellegrin et al. 1999). TAMs have a subtle effect on in vitro ddI susceptibility, with three or more TAMs (particularly M41L, L210W, and T215Y) required to reduce susceptibility by ~1.5 fold. However, despite the minimal effect on in vitro susceptibility, the presence of M41L, L210W, and T215Y is associated with a greatly drediced virological response to ddI intensification (Marcelin et al. 2005; Molina et al. 2005).
M184V occurs in a small proportion of patients receiving ddI monotherapy (usually after development of L74V) but does not occur in patients receiving ddI with ZDV or d4T (Shafer et al. 1994). M184V reduces ddI susceptibility slightly <1.5 fold. In combination with multiple TAMs, M184V contributes to greater reductions in susceptibility (Whitcomb et al. 2003). However, M184V does not appear to reduce the virologic response to ddI, possibly because the M184V-associated decreased RC and the accompanying increased susceptibility to TDF, ZDV, and d4T associated with M184V counter the decrease in ddI susceptibility.
Q151M complex
Usually in combination with V75I, F77L, F116Y
Q151M confers low-level resistance to TDF, 3TC, and FTC, and high-level resistance to each of the remaining NRTIs. In combination with mutations at positions 75, 77, and 116, Q151M confers intermediate resistance to 3TC, FTC, and TDF, and even high-levels of resistance to the remaining NRTIs(Clevenbergh et al. 2002; Deval et al. 2002; Feng et al. 2006; Gallego et al. 2003; Garcia-Lerma et al. 2000; Iversen et al. 1996; Matsumi et al. 2003; Schmit et al. 1998; Shafer et al. 1995; Shafer et al. 1994; Shirasaka et al. 1995; Van Vaerenbergh et al. 2000; Zaccarelli et al. 2004).
T69 insertion mutations
T69 insertions occur in ~1% of treated patients, nearly always in combination with multiple TAMs. Together these mutations cause high-level resistance to each of the NRTIs (Cases-Gonzalez et al. 2006; Clevenbergh et al. 2002; de Jong et al. 1999; Eggink et al. 2007; Gallego et al. 2003; Kew et al. 1998; Larder et al. 1999; Masquelier et al. 2001; Matamoros et al. 2004; Meyer et al. 2003; Rakik et al. 1999; Tamalet et al. 1998; Tamalet et al. 2000; Van Vaerenbergh et al. 2000; White et al. 2004; Winters et al. 1998).
T69D has minimal, if any, effect on ddI susceptibility in vitro. However, in combination with multiple TAMs, these mutations are associated with a decreased virologic response to ddI in vivo (Naugler et al. 2002).
V75T and V75M have each been shown to reduce ddI susceptibility in vitro (Lacey and Larder 1994; Rhee et al. 2006)
E44D +/- V118I
E44D and V118I are accessory mutations that usually occur with multiple TAMs. They contribute some degree of resistance to each of the NRTIs including 3TC and FTC (Delaugerre et al. 2001; Gianotti et al. 2006; Girouard et al. 2003; Hertogs et al. 2000; Lin et al. 1999; Montes and Segondy 2002; Romano et al. 2002).
Clinical Uses
Initial therapy
ddI + 3TC or FTC in combination with an NNRTI have been highly effective first line therapies in several small clinical trials (Saag et al. 2004) and therefore this combination has been classified as alternative NRTI backbone of initial regimens by the US DHHS Guidelines. ddI/d4T is not recommended because of decreased efficacy and increased toxicity. ddI/TDF is not recommended because it has been associated with early virologic failures in patients with high plasma HIV-1 RNA levels (Leon et al. 2005; Podzamczer et al. 2005; Torti et al. 2005). ddI/ZDV has not been widely studied as part of an initial HAART regimen.
Salvage therapy
In patients harboring viruses with M184V and TAMs, ddI has a high genetic barrier to resistance. However, the optimal NRTIs to be used in combination with ddI are not known. ddI/TDF coadministration has been associated with a blunted CD4 response, particularly but not exclusively when ddI is not administered at the appropriately reduced dosage of 250 mg per day for TDF co-administration (Barrios et al. 2005; Clotet et al. 2007; Karrer et al. 2005; Negredo et al. 2005). There are also too few data on the use of ddI in combination with ZDV, 3TC, or ABC, although the latter is not likely to be useful because similar mutations cause resistance to both drugs.
  • Barrios, A., A. Rendon, E. Negredo, P. Barreiro, T. Garcia-Benayas, P. Labarga, J. Santos, P. Domingo, M. Sanchez-Conde, I. Maida, L. Martin-Carbonero, M. Nunez, F. Blanco, B. Clotet, M.A. Sambeat, P. Gil, J. Gonzalez-Lahoz, D. Cooper, and V. Soriano. 2005. Paradoxical CD4+ T-cell decline in HIV-infected patients with complete virus suppression taking tenofovir and didanosine. Aids 19: 569-575.
  • Berkhout, B., N.K. Back, A. de Ronde, S. Jurriaans, M. Bakker, N.T. Parkin, and L. van der Hoek. 2006. Identification of alternative amino acid substitutions in drug-resistant variants of the HIV-1 reverse transcriptase. Aids 20: 1515-1520.
  • Cases-Gonzalez, C.E., S. Franco, M.A. Martinez, and L. Menendez-Arias. 2006. Mutational Patterns Associated with the 69 Insertion Complex in Multi-drug-resistant HIV-1 Reverse Transcriptase that Confer Increased Excision Activity and High-level Resistance to Zidovudine. J Mol Biol.
  • Clevenbergh, P., M. Kirstetter, J.Y. Liotier, M. Dupon, P. Philibert, C. Jacomet, E. Cua, N. Montagne, J.C. Schmit, and P. Dellamonica. 2002. Long-term virological outcome in patients infected with multi-nucleoside analogue-resistant HIV-1. Antivir Ther 7: 305-308.
  • Clotet, B., E. Negredo, P.M. Girard, M. Youle, and D. Neubacher. 2007. Compromised immunologic recovery in patients receiving tipranavir/ritonavir coadministered with tenofovir and didanosine in Randomized Evaluation of Strategic Intervention in multidrug-resiStant patients with tipranavir (RESIST) studies. J Acquir Immune Defic Syndr 45: 479-481.
  • Coakley, E.P., J.M. Gillis, and S.M. Hammer. 2000. Phenotypic and genotypic resistance patterns of HIV-1 isolates derived from individuals treated with didanosine and stavudine. AIDS 14: F9-15.
  • de Jong, J.J., J. Goudsmit, V.V. Lukashov, M.E. Hillebrand, E. Baan, R. Huismans, S.A. Danner, J.H. ten Veen, F. de Wolf, and S. Jurriaans. 1999. Insertion of two amino acids combined with changes in reverse transcriptase containing tyrosine-215 of HIV-1 resistant to multiple nucleoside analogs. AIDS 13: 75-80.
  • Delaugerre, C., M. Mouroux, A. Yvon-Groussin, A. Simon, F. Angleraud, J.M. Huraux, H. Agut, C. Katlama, and V. Calvez. 2001. Prevalence and conditions of selection of E44D/A and V118I human immunodeficiency virus type 1 reverse transcriptase mutations in clinical practice. Antimicrob Agents Chemother 45: 946-948.
  • Deval, J., B. Selmi, J. Boretto, M.P. Egloff, C. Guerreiro, S. Sarfati, and B. Canard. 2002. The molecular mechanism of multidrug resistance by the Q151M human immunodeficiency virus type 1 reverse transcriptase and its suppression using alpha-boranophosphate nucleotide analogues. J Biol Chem 277: 42097-42104.
  • Eggink, D., M.C. Huigen, C.A. Boucher, M. Gotte, and M. Nijhuis. 2007. Insertions in the beta3-beta4 loop of reverse transcriptase of human immunodeficiency virus type 1 and their mechanism of action, influence on drug susceptibility and viral replication capacity. Antiviral Res 75: 93-103.
  • Feng, J.Y., F.T. Myrick, N.A. Margot, G.B. Mulamba, L. Rimsky, K. Borroto-Esoda, B. Selmi, and B. Canard. 2006. Virologic and enzymatic studies revealing the mechanism of K65R- and Q151M-associated HIV-1 drug resistance towards emtricitabine and lamivudine. Nucleosides Nucleotides Nucleic Acids 25: 89-107.
  • Gallego, O., C. d Mendoza, P. Labarga, C. Altisent, J. Gonzalez, I. Garcia-Alcalde, L. Valer, E. Valencia, and V. Soriano. 2003. Long-term outcome of HIV-infected patients with multinucleoside-resistant genotypes. HIV Clin Trials 4: 372-381.
  • Garcia-Lerma, J.G., P.J. Gerrish, A.C. Wright, S.H. Qari, and W. Heneine. 2000. Evidence of a role for the Q151L mutation and the viral background in development of multiple dideoxynucleoside-resistant human immunodeficiency virus type 1. J Virol 74: 9339-9346.
  • Gianotti, N., L. Galli, E. Boeri, A. De Bona, M. Guffanti, A. Danise, S. Salpietro, A. Lazzarin, and A. Castagna. 2006. The 118I reverse transcriptase mutation is the only independent genotypic predictor of virologic failure to a stavudine-containing salvage therapy in HIV-1-infected patients. J Acquir Immune Defic Syndr 41: 447-452.
  • Girouard, M., K. Diallo, B. Marchand, S. McCormick, and M. Gotte. 2003. Mutations E44D and V118I in the reverse transcriptase of HIV-1 play distinct mechanistic roles in dual resistance to AZT and 3TC. J Biol Chem 278: 34403-34410.
  • Hertogs, K., S. Bloor, V. De Vroey, C. van Den Eynde, P. Dehertogh, A. van Cauwenberge, M. Sturmer, T. Alcorn, S. Wegner, M. van Houtte, V. Miller, and B.A. Larder. 2000. A novel human immunodeficiency virus type 1 reverse transcriptase mutational pattern confers phenotypic lamivudine resistance in the absence of mutation 184V. Antimicrob Agents Chemother 44: 568-573.
  • Iversen, A.K., R.W. Shafer, K. Wehrly, M.A. Winters, J.I. Mullins, B. Chesebro, and T.C. Merigan. 1996. Multidrug-resistant human immunodeficiency virus type 1 strains resulting from combination antiretroviral therapy. J.Virol. 70: 1086-1090.
  • Karrer, U., B. Ledergerber, H. Furrer, L. Elzi, M. Battegay, M. Cavassini, A. Gayet-Ageron, B. Hirschel, P. Schmid, M. Russotti, R. Weber, and R.F. Speck. 2005. Dose-dependent influence of didanosine on immune recovery in HIV-infected patients treated with tenofovir. Aids 19: 1987-1994.
  • Kew, Y., L.R. Olsen, A.J. Japour, and V.R. Prasad. 1998. Insertions into the beta3-beta4 hairpin loop of HIV-1 reverse transcriptase reveal a role for fingers subdomain in processive polymerization. J.Biol.Chem. 273: 7529-7537.
  • Kozal, M.J., K. Kroodsma, M.A. Winters, R.W. Shafer, B. Efron, D.A. Katzenstein, and T.C. Merigan. 1994. Didanosine resistance in HIV-infected patients switched from zidovudine to didanosine monotherapy. Ann.Intern.Med. 121: 263-268.
  • Lacey, S.F. and B.A. Larder. 1994. Novel mutation (V75T) in human immunodeficiency virus type 1 reverse transcriptase confers resistance to 2',3'-didehydro-2',3'- dideoxythymidine in cell culture. Antimicrob.Agents Chemother. 38: 1428-1432.
  • Larder, B.A., S. Bloor, S.D. Kemp, K. Hertogs, R.L. Desmet, V. Miller, M. Sturmer, S. Staszewski, J. Ren, D.K. Stammers, D.I. Stuart, and R. Pauwels. 1999. A family of insertion mutations between codons 67 and 70 of human immunodeficiency virus type 1 reverse transcriptase confer multinucleoside analog resistance. Antimicrob Agents Chemother 43: 1961-1967.
  • Leon, A., J. Mallolas, E. Martinez, E. De Lazzari, T. Pumarola, M. Larrousse, A. Milincovic, M. Lonca, J.L. Blanco, M. Laguno, A. Biglia, and J.M. Gatell. 2005. High rate of virological failure in maintenance antiretroviral therapy with didanosine and tenofovir. Aids 19: 1695-1697.
  • Lin, P.F., C.J. Gonzalez, B. Griffith, G. Friedland, V. Calvez, F. Ferchal, R.F. Schinazi, D.H. Shepp, A.B. Ashraf, M.A. Wainberg, V. Soriano, J.W. Mellors, and R.J. Colonno. 1999. Stavudine resistance: an update on susceptibility following prolonged therapy. Antivir.Ther. 4: 21-28.
  • Marcelin, A.G., P. Flandre, J. Pavie, N. Schmidely, M. Wirden, O. Lada, D. Chiche, J.M. Molina, and V. Calvez. 2005. Clinically relevant genotype interpretation of resistance to Didanosine. Antimicrob Agents Chemother 49: 1739-1744.
  • Margot, N.A., J.M. Waters, and M.D. Miller. 2006. In Vitro HIV-1 Resistance Selections with Combinations of Tenofovir and Emtricitabine or Abacavir and Lamivudine. Antimicrob Agents Chemother 50: 4087-4095.
  • Masquelier, B., E. Race, C. Tamalet, D. Descamps, J. Izopet, C. Buffet-Janvresse, A. Ruffault, A.S. Mohammed, J. Cottalorda, A. Schmuck, V. Calvez, E. Dam, H. Fleury, and F. Brun-Vezinet. 2001. Genotypic and phenotypic resistance patterns of human immunodeficiency virus type 1 variants with insertions or deletions in the reverse transcriptase (RT): multicenter study of patients treated with RT inhibitors. Antimicrob Agents Chemother 45: 1836-1842.
  • Matamoros, T., S. Franco, B.M. Vazquez-Alvarez, A. Mas, M.A. Martinez, and L. Menendez-Arias. 2004. Molecular determinants of multi-nucleoside analogue resistance in HIV-1 reverse transcriptases containing a dipeptide insertion in the fingers subdomain: effect of mutations D67N and T215Y on removal of thymidine nucleotide analogues from blocked DNA primers. J Biol Chem 279: 24569-24577.
  • Matsumi, S., P. Kosalaraksa, H. Tsang, M.F. Kavlick, S. Harada, and H. Mitsuya. 2003. Pathways for the emergence of multi-dideoxynucleoside-resistant HIV-1 variants. Aids 17: 1127-1137.
  • Meyer, P.R., J. Lennerstrand, S.E. Matsuura, B.A. Larder, and W.A. Scott. 2003. Effects of dipeptide insertions between codons 69 and 70 of human immunodeficiency virus type 1 reverse transcriptase on primer unblocking, deoxynucleoside triphosphate inhibition, and DNA chain elongation. J Virol 77: 3871-3877.
  • Molina, J.M., A.G. Marcelin, J. Pavie, L. Heripret, C.M. De Boever, M. Troccaz, G. Leleu, and V. Calvez. 2005. Didanosine in HIV-1-infected patients experiencing failure of antiretroviral therapy: a randomized placebo-controlled trial. J Infect Dis 191: 840-847.
  • Montaner, J.S., P. Reiss, D. Cooper, S. Vella, M. Harris, B. Conway, M.A. Wainberg, D. Smith, P. Robinson, D. Hall, M. Myers, and J.M. Lange. 1998. A randomized, double-blind trial comparing combinations of nevirapine, didanosine, and zidovudine for HIV-infected patients: the INCAS Trial. Italy, The Netherlands, Canada and Australia Study. JAMA 279: 930-937.
  • Montes, B. and M. Segondy. 2002. Prevalence of the mutational pattern E44D/A and/or V118I in the reverse transcriptase (RT) gene of HIV-1 in relation to treatment with nucleoside analogue RT inhibitors. J Med Virol 66: 299-303.
  • Naugler, W.E., F.H. Yong, V.J. Carey, J.A. Dragavon, R.W. Coombs, and L.M. Frenkel. 2002. T69D/N pol mutation, human immunodeficiency virus type 1 RNA Levels, and syncytium-inducing phenotype are associated with CD4 cell depletion during didanosine therapy. J Infect Dis 185: 448-455.
  • Negredo, E., A. Bonjoch, R. Paredes, J. Puig, and B. Clotet. 2005. Compromised immunologic recovery in treatment-experienced patients with HIV infection receiving both tenofovir disoproxil fumarate and didanosine in the TORO studies. Clin Infect Dis 41: 901-905. Pellegrin, I., J. Izopet, J. Reynes, M. Denayrolles, B. Montes, J.L. Pellegrin, P. Massip, J. Puel, H. Fleury, and M. Segondy. 1999. Emergence of zidovudine and multidrug-resistance mutations in the HIV-1 reverse transcriptase gene in therapy-naive patients receiving stavudine plus didanosine combination therapy. STADI Group. AIDS 13: 1705-1709.
  • Podzamczer, D., E. Ferrer, J.M. Gatell, J. Niubo, D. Dalmau, A. Leon, H. Knobel, C. Polo, D. Iniguez, and I. Ruiz. 2005. Early virological failure with a combination of tenofovir, didanosine and efavirenz. Antivir Ther 10: 171-177.
  • Rakik, A., M. Ait-Khaled, P. Griffin, T.A. Thomas, M. Tisdale, and J.P. Kleim. 1999. A novel genotype encoding a single amino acid insertion and five other substitutions between residues 64 and 74 of the HIV-1 reverse transcriptase confers high-level cross-resistance to nucleoside reverse transcriptase inhibitors. Abacavir CNA2007 International Study Group. J Acquir Immune Defic Syndr 22: 139-145.
  • Rhee, S.Y., J. Taylor, G. Wadhera, A. Ben-Hur, D.L. Brutlag, and R.W. Shafer. 2006. Genotypic predictors of human immunodeficiency virus type 1 drug resistance. Proc Natl Acad Sci U S A 103: 17355-17360.
  • Romano, L., G. Venturi, S. Bloor, R. Harrigan, B.A. Larder, J.C. Major, and M. Zazzi. 2002. Broad nucleoside-analogue resistance implications for human immunodeficiency virus type 1 reverse-transcriptase mutations at codons 44 and 118. J Infect Dis 185: 898-904.
  • Ross, L.L., R. Dretler, P. Gerondelis, E.G. Rouse, M.L. Lim, and E.R. Lanier. 2006. A rare HIV reverse transcriptase mutation, K65N, confers reduced susceptibility to tenofovir, lamivudine and didanosine. Aids 20: 787-789.
  • Saag, M.S., P. Cahn, F. Raffi, M. Wolff, D. Pearce, J.M. Molina, W. Powderly, A.L. Shaw, E. Mondou, J. Hinkle, K. Borroto-Esoda, J.B. Quinn, D.W. Barry, and F. Rousseau. 2004. Efficacy and safety of emtricitabine vs stavudine in combination therapy in antiretroviral-naive patients: a randomized trial. Jama 292: 180-189.
  • Schmit, J.C., L.K. Van, L. Ruiz, P. Hermans, S. Sprecher, A. Sonnerborg, M. Leal, T. Harrer, B. Clotet, V. Arendt, E. Lissen, M. Witvrouw, J. Desmyter, C.E. De, and A.M. Vandamme. 1998. Multiple dideoxynucleoside analogue-resistant (MddNR) HIV-1 strains isolated from patients from different European countries. AIDS 12: 2007-2015.
  • Shafer, R.W., A.K. Iversen, M.A. Winters, E. Aguiniga, D.A. Katzenstein, and T.C. Merigan. 1995. Drug resistance and heterogeneous long-term virologic responses of human immunodeficiency virus type 1-infected subjects to zidovudine and didanosine combination therapy. The AIDS Clinical Trials Group 143 Virology Team. J.Infect.Dis. 172: 70-78.
  • Shafer, R.W., M.J. Kozal, M.A. Winters, A.K. Iversen, D.A. Katzenstein, M.V. Ragni, W.A. Meyer, P. Gupta, S. Rasheed, R. Coombs, and T.C. Merigan. 1994. Combination therapy with zidovudine and didanosine selects for drug- resistant human immunodeficiency virus type 1 strains with unique patterns of pol gene mutations. J.Infect.Dis. 169: 722-729.
  • Shafer, R.W., L.M. Smeaton, G.K. Robbins, V. De Gruttola, S.W. Snyder, R.T. D'Aquila, V.A. Johnson, G.D. Morse, M.A. Nokta, A.I. Martinez, B.M. Gripshover, P. Kaul, R. Haubrich, M. Swingle, S.D. McCarty, S. Vella, M.S. Hirsch, and T.C. Merigan. 2003. Comparison of four-drug regimens and pairs of sequential three-drug regimens as initial therapy for HIV-1 infection. N Engl J Med 349: 2304-2315.
  • Shirasaka, T., M.F. Kavlick, T. Ueno, W.Y. Gao, E. Kojima, M.L. Alcaide, S. Chokekijchai, B.M. Roy, E. Arnold, R. Yarchoan, and H. Mitsuya. 1995. Emergence of human immunodeficiency virus type 1 variants with resistance to multiple dideoxynucleosides in patients receiving therapy with dideoxynucleosides. Proc.Natl.Acad.Sci.U.S.A. 92: 2398-2402.
  • St. Clair, M., J.L. Martin, G. Tudor-Williams, M.C. Bach, C.L. Vavro, D.M. King, P. Kellam, S.D. Kemp, and B.A. Larder. 1991. Resistance to ddI and sensitivity to AZT induced by a mutation in HIV-1 reverse transcriptase. Science 253: 1557-1559.
  • Tamalet, C., J. Izopet, N. Koch, J. Fantini, and N. Yahi. 1998. Stable rearrangements of the beta3-beta4 hairpin loop of HIV-1 reverse transcriptase in plasma viruses from patients receiving combination therapy. AIDS 12: F161-166.
  • Tamalet, C., N. Yahi, C. Tourres, P. Colson, A.M. Quinson, I. Poizot-Martin, C. Dhiver, and J. Fantini. 2000. Multidrug resistance genotypes (insertions in the beta3-beta4 finger subdomain and MDR mutations) of HIV-1 reverse transcriptase from extensively treated patients: incidence and association with other resistance mutations. Virology 270: 310-316. Torti, C., E. Quiros-Roldon, M. Regazzi, A. Antinori, A. Patroni, P. Villani, V. Tirelli, G. Cologni, D. Zinzi, S. Lo Caputo, P. Perini, and G. Carosi. 2005. Early virological failure after tenofovir + didanosine + efavirenz combination in HIV-positive patients upon starting antiretroviral therapy. Antivir Ther 10: 505-513.
  • Van Vaerenbergh, K., K. Van Laethem, J. Albert, C.A. Boucher, B. Clotet, M. Floridia, J. Gerstoft, B. Hejdeman, C. Nielsen, C. Pannecouque, L. Perrin, M.F. Pirillo, L. Ruiz, J.C. Schmit, F. Schneider, A. Schoolmeester, R. Schuurman, H.J. Stellbrink, L. Stuyver, J. Van Lunzen, B. Van Remoortel, E. Van Wijngaerden, S. Vella, M. Witvrouw, S. Yerly, E. De Clercq, J. Destmyer, and A.M. Vandamme. 2000. Prevalence and characteristics of multinucleoside-resistant human immunodeficiency virus type 1 among European patients receiving combinations of nucleoside analogues. Antimicrob Agents Chemother 44: 2109-2117. <
  • LI>Whitcomb, J.M., N.T. Parkin, C. Chappey, N.S. Hellmann, and C.J. Petropoulos. 2003. Broad nucleoside reverse-transcriptase inhibitor cross-resistance in human immunodeficiency virus type 1 clinical isolates. J Infect Dis 188: 992-1000.
  • White, K.L., J.M. Chen, N.A. Margot, T. Wrin, C.J. Petropoulos, L.K. Naeger, S. Swaminathan, and M.D. Miller. 2004. Molecular mechanisms of tenofovir resistance conferred by human immunodeficiency virus type 1 reverse transcriptase containing a diserine insertion after residue 69 and multiple thymidine analog-associated mutations. Antimicrob Agents Chemother 48: 992-1003.
  • Winters, M.A., K.L. Coolley, Y.A. Girard, D.J. Levee, H. Hamdan, R.W. Shafer, D.A. Katzenstein, and T.C. Merigan. 1998. A 6-basepair insert in the reverse transcriptase gene of human immunodeficiency virus type 1 confers resistance to multiple nucleoside inhibitors. J.Clin.Invest. 102: 1769-1775.
  • Winters, M.A., R.W. Shafer, R.A. Jellinger, G. Mamtora, T. Gingeras, and T.C. Merigan. 1997. Human immunodeficiency virus type 1 reverse transcriptase genotype and drug susceptibility changes in infected individuals receiving dideoxyinosine monotherapy for 1 to 2 years. Antimicrob.Agents Chemother. 41: 757-762. Zaccarelli, M., C.F. Perno, F. Forbici, F. Soldani, S. Bonfigli, C. Gori, M.P. Trotta, M.C. Bellocchi, G. Liuzzi, R. D'Arrigo, P. De Longis, E. Boumis, R. Bellagamba, V. Tozzi, P. Narciso, and A. Antinori. 2004. Q151M-mediated multinucleoside resistance: prevalence, risk factors, and response to salvage therapy. Clin Infect Dis 38: 433-437.