JAC Advance Access originally published online on January 25, 2008
Journal of Antimicrobial Chemotherapy 2008 61(3):705-713; doi:10.1093/jac/dkm522
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Original research |
What is the risk of mortality following diagnosis of multidrug-resistant HIV-1?
1 Centre of Sexual Health and HIV Research, Department of Primary Care and Population Sciences, Mortimer Market Centre, London, UK 2 HIV and Infectious Diseases Group, Medical Research Council Clinical Trials Unit, London, UK 3 The Mortimer Market Centre, Department of Genitourinary Medicine, Camden PCT, London, UK 4 Department of Primary Care and Population Sciences, Royal Free and University College Medical School, London, UK 5 Centre of Virology, Department of Infection, Royal Free and University College Medical School, London, UK 6 Centre for Infections, Health Protection Agency, London, UK
Received 1 October 2007; returned 6 December 2007; revised 26 October 2007; accepted 9 December 2007
* Correspondence address. HIV/Genitourinary Medicine, St Stephen’s Centre, Chelsea and Westminster Hospital, London SW10 9TH, UK. Tel: +44-20-8846-6148; Fax: +44-20-8846-6198; E-mail: deepa.grover{at}chelwest.nhs.uk
Objectives: To estimate the risk of death and examine the predictors of death and virological/immunological response, following diagnosis of multidrug-resistant (MDR) HIV-1 in a UK multicentre cohort of HIV-infected individuals.
Methods: Five hundred and seventy-two patients were identified with MDR HIV-1 between 1997 and 2004. Factors associated with survival and virological/immunological response 24–48 weeks after MDR diagnosis were determined by the Poisson and linear regression, respectively.
Results: Patient characteristics: 86% males; median age 39 years; median CD4 and viral load (VL) at MDR diagnosis 230 cells/mm3 and 4.2 log10copies/mL; median number of antiretroviral drugs previously exposed to 8. Sixty patients died over a median follow-up of 31 months (IQR: 17–50), giving an estimated mortality rate of 3.7 deaths per 100 person-years (95% CI 2.9–4.7) following MDR diagnosis. In adjusted analysis, higher CD4 count, lower VL, more recent calendar year, lower number of antiretroviral drugs previously exposed to and greater age at MDR diagnosis were associated with an increased chance of survival. There was some evidence of a better virological response at 24–48 weeks after MDR diagnosis in patients who changed regimen compared with patients who did not change regimen.
Conclusions: The risk of death following MDR diagnosis may be at least 3-fold the risk observed overall in HIV-infected individuals. Changing antiretroviral therapy following emergence of MDR HIV-1 may be associated with improved short-term virological response.
Keywords: MDR HIV-1 , genotypic sensitivity score , antiretroviral therapy
See the Acknowledgements section for membership of Steering Committees.