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Trends in Decline of Antiretroviral Resistance among ARV-Experienced Patients in the HIV Outpatient Study: 1999–2008

DOI: 10.1155/2012/230290

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Background. Little is known about temporal trends in frequencies of clinically relevant ARV resistance mutations in HIV strains from U.S. patients undergoing genotypic testing (GT) in routine HIV care. Methods. We analyzed cumulative frequency of HIV resistance among patients in the HIV Outpatient Study (HOPS) who, during 1999–2008 and while prescribed antiretrovirals, underwent GT with plasma HIV RNA >1,000 copies/mL. Exposure ≥4 months to each of three major antiretroviral classes (NRTI, NNRTI and PI) was defined as triple-class exposure (TCE). Results. 906 patients contributed 1,570 GT results. The annual frequency of any major resistance mutations decreased during 1999–2008 (88% to 79%, ). Resistance to PIs decreased among PI-exposed patients (71% to 46%, ) as exposure to ritonavir-boosted PIs increased (6% to 81%, ). Non-significant declines were observed in resistance to NRTIs among NRTI-exposed (82% to 67%), and triple-class-resistance among TCE patients (66% to 41%), but not to NNRTIs among NNRTI-exposed. Conclusions. HIV resistance was common but declined in HIV isolates from subgroups of ARV-experienced HOPS patients during 1999–2008. Resistance to PIs among PI-exposed patients decreased, possibly due to increased representation of patients whose only PI exposures were to boosted PIs. 1. Introduction Highly active combination antiretroviral therapy (cART) has significantly improved survival and reduced the rates of AIDS-related complications among HIV-infected persons [1–3]. Emergence of HIV variants with reduced susceptibility to antiretroviral (ARV) medications can significantly limit the effectiveness and durability of treatment [3–8]. Use of ARV resistance testing to optimize cART selection has been associated with better virologic and clinical outcomes [9–11] and improved survival [12], and resistance testing is now generally recommended in the clinical management of HIV infection [13–15]. We have previously shown that use of genotypic and phenotypic testing increased in the HIV Outpatient Study (HOPS) during 1999–2006 and that the likelihood of testing varied by HIV disease severity and demographic characteristics [16]. Recent European and Canadian studies have suggested that both the prevalence [17, 18] and incidence [19, 20] of ARV resistance among HIV-infected persons have declined, due predominately to a decrease in the proportion of patients with pre-cART mono- or dual-ARV experience, and the increasing use and effectiveness of more tolerable and potent cART regimens that appear less likely to result in resistance mutations [18–22].


[1]  F. J. Palella Jr., K. M. Delaney, A. C. Moorman et al., “Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection,” New England Journal of Medicine, vol. 338, no. 13, pp. 853–860, 1998.
[2]  A. Mocroft, B. Ledergerber, C. Katlama et al., “Decline in the AIDS and death rates in the EuroSIDA study: an observational study,” The Lancet, vol. 362, no. 9377, pp. 22–29, 2003.
[3]  A. Cozzi-Lepri, A. N. Phillips, B. Clotet et al., “Detection of HIV drug resistance during antiretroviral treatment and clinical progression in a large European cohort study,” AIDS, vol. 22, no. 16, pp. 2187–2198, 2008.
[4]  A. N. Phillips, C. Leen, A. Wilson et al., “Risk of extensive virological failure to the three original antiretroviral drug classes over long-term follow-up from the start of therapy in patients with HIV infection: an observational cohort study,” The Lancet, vol. 370, no. 9603, pp. 1923–1928, 2007.
[5]  R. S. Hogg, D. R. Bangsberg, V. D. Lima et al., “Emergence of drug resistance is associated with an increased risk of death among patients first starting HAART,” PLoS Medicine, vol. 3, no. 9, Article ID e356, 2006.
[6]  G. M. Lucas, J. E. Gallant, and R. D. Moore, “Relationship between drug resistance and HIV-1 disease progression or death in patients undergoing resistance testing,” AIDS, vol. 18, no. 11, pp. 1539–1548, 2004.
[7]  S. G. Deeks, S. J. Gange, M. M. Kitahata et al., “Trends in multidrug treatment failure and subsequent mortality among antiretroviral therapy-experienced patients with HIV infection in North America,” Clinical Infectious Diseases, vol. 49, no. 10, pp. 1582–1590, 2009.
[8]  N. Lohse, L. B. J?rgensen, G. Kronborg et al., “Genotypic drug resistance and long-term mortality in patients with triple-class antiretroviral drug failure,” Antiviral Therapy, vol. 12, no. 6, pp. 909–917, 2007.
[9]  E. T. Panidou, T. A. Trikalinos, and J. P. A. Ioannidis, “Limited benefit of antiretroviral resistance testing in treatment-experienced patients: a meta-analysis,” AIDS, vol. 18, no. 16, pp. 2153–2161, 2004.
[10]  S. A. Wegner, M. R. Wallace, N. E. Aronson et al., “Long-term efficacy of routine access to antiretroviral-resistance testing in HIV type 1-infected patients: results of the clinical efficacy of resistance testing trial,” Clinical Infectious Diseases, vol. 38, no. 5, pp. 723–730, 2004.
[11]  A. Cingolani, A. Antinori, M. G. Rizzo et al., “Usefulness of monitoring HIV drug resistance and adherence in individuals failing highly active antiretroviral therapy: a randomized study (Argenta),” AIDS, vol. 16, no. 3, pp. 369–379, 2002.
[12]  F. J. Palella Jr., C. Armon, K. Buchacz et al., “The association of HIV susceptibility testing with survival among HIV-infected patients receiving antiretroviral therapy: a cohort study,” Annals of Internal Medicine, vol. 151, no. 2, pp. 73–84, 2009.
[13]  M. S. Hirsch, F. Brun-Vézinet, B. Clotet et al., “Antiretroviral drug resistance testing in adults infected with human immunodefidency virus type 1: 2003 recommendations of an International AIDS Society-USA panel,” Clinical Infectious Diseases, vol. 37, no. 1, pp. 113–128, 2003.
[14]  S. M. Hammer, J. J. Eron Jr., P. Reiss et al., “Antiretroviral treatment of adult HIV infection: 2008 Recommendations of the International AIDS Society-USA panel,” Journal of the American Medical Association, vol. 300, no. 5, pp. 555–570, 2008.
[15]  Department of Health and Human Services Panel on Antiretroviral, “Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1 infected adults and adolescents,” pp. 12–17, 2009.
[16]  K. Buchacz, R. K. Baker, B. Young, and J. T. Brooks, “Changes in the use of HIV antiretroviral resistance testing in a large cohort of U.S. Patients, 1999 to 2006,” Journal of Acquired Immune Deficiency Syndromes, vol. 53, no. 5, pp. 625–632, 2010.
[17]  V. Von Wyl, S. Yerly, J. B?ni et al., “Long-term trends of HIV Type 1 drug resistance prevalence among antiretroviral treatment-experienced patients in Switzerland,” Clinical Infectious Diseases, vol. 48, no. 7, pp. 979–987, 2009.
[18]  V. D. Lima, V. S. Gill, B. Yip, R. S. Hogg, J. S. G. Montaner, and P. R. Harrigan, “Increased resilience to the development of drug resistance with modern boosted protease inhibitor-based highly active antiretroviral therapy,” Journal of Infectious Diseases, vol. 198, no. 1, pp. 51–58, 2008.
[19]  V. S. Gill, V. D. Lima, W. Zhang et al., “Improved virological outcomes in British Columbia concomitant with decreasing incidence of HIV type 1 drug resistance detection,” Clinical Infectious Diseases, vol. 50, no. 1, pp. 98–105, 2010.
[20]  A. M. Audelin, N. Lohse, N. Obel, J. Gerstoft, and L. B. J?rgensen, “The incidence rate of HIV type-1 drug resistance in patients on antiretroviral therapy: a nationwide population-based Danish cohort study 1999–2005,” Antiviral Therapy, vol. 14, no. 7, pp. 995–1000, 2009.
[21]  R. K. Gupta, A. Hill, A. W. Sawyer et al., “Virological monitoring and resistance to first-line highly active antiretroviral therapy in adults infected with HIV-1 treated under WHO guidelines: a systematic review and meta-analysis,” The Lancet Infectious Diseases, vol. 9, no. 7, pp. 409–417, 2009.
[22]  V. Von Wyl, S. Yerly, J. B?ni et al., “Emergence of HIV-1 drug resistance in previously untreated patients initiating combination antiretroviral treatment: a comparison of different regimen types,” Archives of Internal Medicine, vol. 167, no. 16, pp. 1782–1790, 2007.
[23]  D. D. Richman, S. C. Morton, T. Wrin et al., “The prevalence of antiretroviral drug resistance in the United States,” AIDS, vol. 18, no. 10, pp. 1393–1401, 2004.
[24]  S. J. Gange, M. F. Schneider, R. M. Grant et al., “Genotypic resistance and immunologic outcomes among HIV-1-infected women with viral failure,” Journal of Acquired Immune Deficiency Syndromes, vol. 41, no. 1, pp. 68–74, 2006.
[25]  S. Napravnik, J. R. Keys, E. B. Quinlivan, D. A. Wohl, O. V. Mikeal, and J. J. Eron, “Triple-class antiretroviral drug resistance: risk and predictors among HIV-1-infected patients,” AIDS, vol. 21, no. 7, pp. 825–834, 2007.
[26]  A. C. Moorman, S. D. Holmberg, S. I. Marlowe et al., “Changing conditions and treatments in a dynamic cohort of ambulatory HIV patients: the HIV outpatient study (HOPS),” Annals of Epidemiology, vol. 9, no. 6, pp. 349–357, 1999.
[27]  A. G. Abraham, B. Lau, S. Deeks et al., “Missing data on the estimation of the prevalence of accumulated human immunodeficiency virus drug resistance in patients treated with antiretroviral drugs in North America,” American Journal of Epidemiology, vol. 174, no. 6, pp. 727–735, 2011.
[28]  P. R. Harrigan, R. S. Hogg, W. W. Y. Dong et al., “Predictors of HIV drug-resistance mutations in a large antiretroviral-naive cohort initiating triple antiretroviral therapy,” Journal of Infectious Diseases, vol. 191, no. 3, pp. 339–347, 2005.
[29]  L. Bansi, C. Smith, A. Phillips et al., “The impact of HIV drug resistance testing on changes to treatment,” AIDS, vol. 25, no. 5, pp. 603–610, 2011.


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