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Triple-class HIV antiretroviral therapy failure in an Australian primary care setting

Mark Bloch A D , Maria Farris B , Dominic Tilden C , Andrew Gowers A and Nicola Cunningham A

A Holdsworth House Medical Practice, Darlinghurst, NSW 2010, Australia.

B Research Development Unit, Merck Sharp & Dohme (Australia) Pty Limited, South Granville, NSW 2142, Australia.

C THEMA Consulting Pty Ltd, Pyrmont, NSW 2009, Australia.

D Corresponding author. Email:

Sexual Health 7(1) 17-24
Submitted: 6 April 2009  Accepted: 8 December 2009   Published: 15 February 2010


Objective: To determine the prevalence, characteristics and virological outcomes of triple-class antiretroviral drug failure (TCF) and triple-class virological failure (TCVF) in HIV-infected patients attending an Australian high caseload primary care clinic. Methods: Cross-sectional observational study using a retrospective review of electronic medical records from 1007 patients with HIV attending Holdsworth House Medical Practice in Darlinghurst, Australia, between 2007 and 2008. TCF was defined as failure (virological, immunological, clinical, intolerance or other) of at least one drug in each of the three major classes of highly active antiretroviral therapy. Results: A total of 51 patients (5.1%) with TCF were identified. Of these patients, 31.4% had experienced virological failure of each of the three main drug classes. Eighty-eight percent of patients with TCF and 75% of patients with TCVF had achieved virological suppression (HIV RNA <400 copies mL–1). Total mean (s.d.) duration on antiretroviral therapy (ART) was 12.2 (3.3) years, with patients receiving an average of 18 antiretroviral drugs during this period. Reasons for treatment change included intolerance (88% of patients), virological failure (84%), immunological failure (24%) and poor adherence (20%). Conclusions: The prevalence of TCF and TCVF in patients with long-term HIV infection and extensive antiretroviral experience is low in primary care sites. Despite experiencing failure to the three main classes of ART, successful virological outcomes are still achievable in the majority of such patients.

Additional keywords: antiretroviral treatment change, triple-class failure, triple-class virological failure.


[1]  Bhaskaran K Hamouda O Sannes M Boufassa F Johnson AM Lambert PC et al 2008 Changes in the risk of death after HIV seroconversion compared with mortality in the general population. JAMA 300 51 9 doi:10.1001/jama.300.1.51

[2]  The Antiretroviral Therapy Cohort Collaboration 2008 Life expectancy of individuals on combination antiretroviral therapy in high-income countries: a collaborative analysis of 14 cohort studies. Lancet 372 293 9 doi:10.1016/S0140-6736(08)61113-7

[3]  Lima VD Hogg RS Harrigan PR Moore D Yip B Wood E et al 2007 Continued improvement in survival among HIV-infected individuals with newer forms of highly active antiretroviral therapy. AIDS 21 685 92 doi:10.1097/QAD.0b013e32802ef30c

[4]  Mocroft A Ledergerber B Katlama C Kirk O Reiss P d’Arminio Monforte A et al 2003 Decline in the AIDS and death rates in the EuroSIDA study: an observational study. Lancet 362 22 9 doi:10.1016/S0140-6736(03)13802-0

[5]  Palella FJ Delaney KM Moorman AC Loveless MO Fuhrer J Satten GA et al 1998 Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. N Engl J Med 338 853 60 doi:10.1056/NEJM199803263381301

[6]  Cozzi-Lepri A Phillips AN Clotet B Mocroft A Ruiz L Kirk O et al 2008 Detection of HIV drug resistance during antiretroviral treatment and clinical progression in a large European cohort study. AIDS 22 2187 98 doi:10.1097/QAD.0b013e328310e04f

[7]  Hogg RS Bangsberg DR Lima VD Alexander C Bonner S Yip B et al 2006 Emergence of drug resistance is associated with an increased risk of death among patients first starting HAART. PLoS Med 3 e356 doi:10.1371/journal.pmed.0030356

[8]  Kozal MJ Huppler Hullsiek K MacArthur RD van den Berg-Wolf M Peng G Xiang Y et al 2007 The incidence of HIV drug resistance and its impact on progression of HIV disease among antiretroviral-naive participants started on three different antiretroviral therapy strategies. HIV Clin Trials 8 357 70 doi:10.1310/hct0806-357

[9]  Lohse N Jørgensen LB Kronborg G Møller A Kvinesdal B Sørensen HT et al 2007 Genotypic drug resistance and long-term mortality in patients with triple-class antiretroviral drug failure. Antivir Ther 12 909 17

[10]  Gross R Yip B Lo Re V Wood E Alexander CS Harrigan PR et al 2006 A simple, dynamic measure of antiretroviral therapy adherence predicts failure to maintain HIV-1 suppression. J Infect Dis 194 1108 14

[11]  Lima VD Harrigan R Murray M Moore DM Wood E Hogg RS et al 2008 Differential impact of adherence on long-term treatment response among naive HIV-infected individuals. AIDS 22 2371 80 doi:10.1097/QAD.0b013e328315cdd3

[12]  Stone VE Jordan J Tolson J Miller R Pilon T 2004 Perspectives on adherence and simplicity for HIV-infected patients on antiretroviral therapy: self-report of the relative importance of multiple attributes of highly active antiretroviral therapy (HAART) regimens in predicting adherence. J Acquir Immune Defic Syndr 36 808 16 doi:10.1097/00126334-200407010-00007

[13]  Monforte AA Lepri AC Rezza G Pezzotti P Antinori A Phillips AN et al 2000 Insights into the reasons for discontinuation of the first highly active antiretroviral therapy (HAART) regimen in a cohort of antiretroviral naïve patients. AIDS 14 499 507 doi:10.1097/00002030-200003310-00005

[14]  Haddow LJ Wood CW Ainsworth JG 2007 Discontinuation of non-nucleoside reverse transcriptase inhibitor-based highly active antiretroviral therapy due to nucleoside analogue reverse transcriptase inhibitor-related metabolic toxicity. Int J STD AIDS 18 343 6 doi:10.1258/095646207780749790

[15]  Hart E Curtis H Wilkins E Johnson M 2007 National review of first treatment change after starting highly active antiretroviral therapy in antiretroviral-naïve patients. HIV Med 8 186 91 doi:10.1111/j.1468-1293.2007.00451.x

[16]  Le Moing V Chêne G Leport C Lewden C Duran S Garré M et al 2002 Impact of discontinuation of initial protease inhibitor therapy on further virological response in a cohort of human immunodeficiency virus-infected patients. Clin Infect Dis 34 239 47 doi:10.1086/324354

[17]  Lodwick RK Smith CJ Youle M Lampe FC Tyrer M Bhagani S et al 2008 Stability of antiretroviral regimens in patients with viral suppression. AIDS 22 1039 46 doi:10.1097/QAD.0b013e3282fec415

[18]  O’Brien ME Clark RA Besch CL Myers L Kissinger P 2003 Patterns and correlates of discontinuation of the initial HAART regimen in an urban outpatient cohort. J Acquir Immune Defic Syndr 34 407 14 doi:10.1097/00126334-200312010-00008

[19]  Vo TT Ledergerber B Keiser O Hirschel B Furrer H Battegay M et al 2008 Durability and outcome of initial antiretroviral treatments received during 2000–2005 by patients in the Swiss HIV Cohort Study. J Infect Dis 197 1685 94 doi:10.1086/588141

[20]  Australian ARV Guidelines Panel. Australian commentary on guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents (November 3, 2008). Available at: (accessed 12 January 2009).

[21]  Hammer SM Eron JJ Reiss P Schooley RT Thompson MA Walmsley S et al 2008 Antiretroviral treatment of adult HIV infection: 2008 recommendations of the International AIDS Society-USA panel. JAMA 300 555 70 doi:10.1001/jama.300.5.555

[22]  Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents (November 3, 2008). Department of Health and Human Services. Available at: ContentFiles/AdultandAdolescentGL.pdf (accessed 12 December 2008).

[23]  Mocroft A Ledergerber B Viard JP Staszewski S Murphy M Chiesi A et al 2004 Time to virological failure of 3 classes of antiretrovirals after initiation of highly active antiretroviral therapy: results from the EuroSIDA study group. J Infect Dis 190 1947 56 doi:10.1086/425424

[24]  Lohse N Obel N Kronborg G Laursen A Pedersen C Larsen CS et al 2005 Declining risk of triple-class antiretroviral drug failure in Danish HIV-infected individuals. AIDS 19 815 22 doi:10.1097/01.aids.0000168976.51843.9f

[25]  Mocroft A Horban A Clotet B d’Arminio Monforte A Bogner JR Aldins P et al 2008 Regional differences in the risk of triple class failure in European patients starting combination antiretroviral therapy after 1 January 1999. HIV Med 9 41 6

[26]  Phillips AN Leen C Wilson A Anderson J Dunn D Schwenk A et al 2007 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. Lancet 370 1923 8

[27]  National Centre in HIV Epidemiology and Clinical Research. HIV/AIDS, viral hepatitis and sexually transmissible infections in Australia: annual surveillance report 2008. National Centre in HIV Epidemiology and Clinical Research: The University of New South Wales, Sydney, Australia.

[28]  Johnson VA Brun-Vezinet F Clotet B Günthard HF Kuritzkes DR Pillay D et al 2008 Update of the drug resistance mutations in HIV-1: December 2008. Top HIV Med 16 138 45

[29]  Martin M Del Cacho E Codina C Tuset M De Lazzari E Mallolas J et al 2008 Relationship between adherence level, type of antiretroviral regimen, and plasma HIV type 1 RNA viral load: a prospective cohort study. AIDS Res Hum Retroviruses 24 1263 8

[30]  Dorrucci M Pezzotti P Grisorio B Minardi C Muro MS Vullo V et al 2001 Time to discontinuation of the first highly active antiretroviral therapy regimen: a comparison between protease inhibitor- and non-nucleoside reverse transcriptase inhibitor-containing regimens. AIDS 15 1733 6 doi:10.1097/00002030-200109070-00020

[31]  Hänsel A Bucher HC Nüesch R Battegay M 2001 Reasons for discontinuation of first highly active antiretroviral therapy in a cohort of proteinase inhibitor-naive HIV-infected patients. J Acquir Immune Defic Syndr 26 191 3 doi:10.1097/00126334-200102010-00016

[32]  Mocroft A Youle M Moore A Sabin CA Madge S Cozzi Lepri A et al 2001 Reasons for modification and discontinuation of antiretrovirals: results from a single treatment centre. AIDS 15 185 94 doi:10.1097/00002030-200101260-00007

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