Sexual Health Sexual Health Society
Publishing on sexual health from the widest perspective
RESEARCH ARTICLE

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
+ Author Affiliations
- Author Affiliations

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: mbloch@holdsworthhouse.com.au

Sexual Health 7(1) 17-24 https://doi.org/10.1071/SH09039
Submitted: 6 April 2009  Accepted: 8 December 2009   Published: 15 February 2010

Abstract

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.


Acknowledgements

We thank the patients with HIV/AIDS and their treating physicians, Dick Quan, David Austin, Ercel Oszer and Hsin-Hua Liu, at HHMP (Darlinghurst, Australia) for granting access to medical histories and participating in the study. We also thank Tim Hughes and Kate Beileiter (Clinical Research Unit, HHMP) for assisting in the conduct of the study and Ann Nestorowicz (Health Interactions, Crows Nest, Australia) for editorial assistance. This study was sponsored and supported by a grant from Merck Sharp & Dohme (Australia) Pty Limited.


References


[1] Bhaskaran K,  Hamouda O,  Sannes M,  Boufassa F,  Johnson AM,  Lambert PC, et al. Changes in the risk of death after HIV seroconversion compared with mortality in the general population. JAMA 2008; 300 51–9.
CrossRef | CAS | PubMed |

[2] The Antiretroviral Therapy Cohort Collaboration Life expectancy of individuals on combination antiretroviral therapy in high-income countries: a collaborative analysis of 14 cohort studies. Lancet 2008; 372 293–9.
CrossRef | PubMed |

[3] Lima VD,  Hogg RS,  Harrigan PR,  Moore D,  Yip B,  Wood E, et al. Continued improvement in survival among HIV-infected individuals with newer forms of highly active antiretroviral therapy. AIDS 2007; 21 685–92.
CrossRef | PubMed |

[4] Mocroft A,  Ledergerber B,  Katlama C,  Kirk O,  Reiss P,  d’Arminio Monforte A, et al. Decline in the AIDS and death rates in the EuroSIDA study: an observational study. Lancet 2003; 362 22–9.
CrossRef | CAS | PubMed |

[5] Palella FJ,  Delaney KM,  Moorman AC,  Loveless MO,  Fuhrer J,  Satten GA, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. N Engl J Med 1998; 338 853–60.
CrossRef | PubMed |

[6] Cozzi-Lepri A,  Phillips AN,  Clotet B,  Mocroft A,  Ruiz L,  Kirk O, et al. Detection of HIV drug resistance during antiretroviral treatment and clinical progression in a large European cohort study. AIDS 2008; 22 2187–98.
CrossRef | CAS | PubMed |

[7] Hogg RS,  Bangsberg DR,  Lima VD,  Alexander C,  Bonner S,  Yip B, et al. Emergence of drug resistance is associated with an increased risk of death among patients first starting HAART. PLoS Med 2006; 3 e356.
CrossRef | PubMed |

[8] Kozal MJ,  Huppler Hullsiek K,  MacArthur RD,  van den Berg-Wolf M,  Peng G,  Xiang Y, et al. 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 2007; 8 357–70.
CrossRef | PubMed |

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

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

[11] Lima VD,  Harrigan R,  Murray M,  Moore DM,  Wood E,  Hogg RS, et al. Differential impact of adherence on long-term treatment response among naive HIV-infected individuals. AIDS 2008; 22 2371–80.
CrossRef | PubMed |

[12] Stone VE,  Jordan J,  Tolson J,  Miller R,  Pilon T. 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 2004; 36 808–16.
CrossRef | PubMed |

[13] Monforte AA,  Lepri AC,  Rezza G,  Pezzotti P,  Antinori A,  Phillips AN, et al. Insights into the reasons for discontinuation of the first highly active antiretroviral therapy (HAART) regimen in a cohort of antiretroviral naïve patients. AIDS 2000; 14 499–507.
CrossRef | PubMed |

[14] Haddow LJ,  Wood CW,  Ainsworth JG. 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 2007; 18 343–6.
CrossRef | CAS | PubMed |

[15] Hart E,  Curtis H,  Wilkins E,  Johnson M. National review of first treatment change after starting highly active antiretroviral therapy in antiretroviral-naïve patients. HIV Med 2007; 8 186–91.
CrossRef | CAS | PubMed |

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

[17] Lodwick RK,  Smith CJ,  Youle M,  Lampe FC,  Tyrer M,  Bhagani S, et al. Stability of antiretroviral regimens in patients with viral suppression. AIDS 2008; 22 1039–46.
CrossRef | CAS | PubMed |

[18] O’Brien ME,  Clark RA,  Besch CL,  Myers L,  Kissinger P. Patterns and correlates of discontinuation of the initial HAART regimen in an urban outpatient cohort. J Acquir Immune Defic Syndr 2003; 34 407–14.
CrossRef | PubMed |

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

[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: http://www.ashm.org.au/aust-guidelines (accessed 12 January 2009).

[21] Hammer SM,  Eron JJ,  Reiss P,  Schooley RT,  Thompson MA,  Walmsley S, et al. Antiretroviral treatment of adult HIV infection: 2008 recommendations of the International AIDS Society-USA panel. JAMA 2008; 300 555–70.
CrossRef | CAS | PubMed |

[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: http://www.aidsinfo.nih.gov/ ContentFiles/AdultandAdolescentGL.pdf (accessed 12 December 2008).

[23] Mocroft A,  Ledergerber B,  Viard JP,  Staszewski S,  Murphy M,  Chiesi A, et al. 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 2004; 190 1947–56.
CrossRef | CAS | PubMed |

[24] Lohse N,  Obel N,  Kronborg G,  Laursen A,  Pedersen C,  Larsen CS, et al. Declining risk of triple-class antiretroviral drug failure in Danish HIV-infected individuals. AIDS 2005; 19 815–22.
CrossRef | CAS | PubMed |

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

[26] Phillips AN,  Leen C,  Wilson A,  Anderson J,  Dunn D,  Schwenk A, 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. Lancet 2007; 370 1923–8.
CrossRef | CAS | PubMed |

[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. Update of the drug resistance mutations in HIV-1: December 2008. Top HIV Med 2008; 16 138–45.
PubMed |

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

[30] Dorrucci M,  Pezzotti P,  Grisorio B,  Minardi C,  Muro MS,  Vullo V, et al. 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 2001; 15 1733–6.
CrossRef | CAS | PubMed |

[31] Hänsel A,  Bucher HC,  Nüesch R,  Battegay M. Reasons for discontinuation of first highly active antiretroviral therapy in a cohort of proteinase inhibitor-naive HIV-infected patients. J Acquir Immune Defic Syndr 2001; 26 191–3.
CrossRef | PubMed |

[32] Mocroft A,  Youle M,  Moore A,  Sabin CA,  Madge S,  Cozzi Lepri A, et al. Reasons for modification and discontinuation of antiretrovirals: results from a single treatment centre. AIDS 2001; 15 185–94.
CrossRef | CAS | PubMed |



Rent Article (via Deepdyve) Export Citation Cited By (1)