Multiple drug class-wide resistance associated with poorer survival after treatment failure in a cohort of HIV-infected patients

Clinical Department bLaboratory of Antiviral Drug Monitoring, National Institute of Infectious Diseases Lazzaro Spallanzani, IRCCS, Rome, Italy.
AIDS (Impact Factor: 6.56). 08/2005; 19(10):1081-9. DOI: 10.1097/
Source: PubMed

ABSTRACT To evaluate the effect of drug class-wide resistance (CWR) on survival in HIV-infected individuals who underwent genotypic resistance test after antiretroviral failure.
Observational, longitudinal cohort study.
HIV-infected individuals experiencing treatment failure were enrolled at first genotypic resistance test. End-points were death for any cause, AIDS-related death and AIDS-defining event/death. CWR was defined according to the International AIDS Society consensus. Survival analysis was performed with Cox's model.
Among 623 patients enrolled and followed for a median of 19 months (interquartile range, 12-29), Kaplan-Meier analyses for end-points at 48 months in patients with no CWR, one CWR, two CWR or three CWR were 8.9, 11.7, 13.4 and 27.1%, respectively, for death; 6.1, 9.9, 13.4 and 21.5%, respectively, for AIDS-related death; and 16.0, 17.7, 19.3 and 35.9%, respectively, for new AIDS event/death. In a multivariate Cox's model, higher HIV RNA level, previous AIDS and detection of three CWR (hazard ratio, 5.34; 95% confidence interval, 1.76-16.24) were all significantly associated with increased risk of death, while higher CD4 cell count and use of a new boosted protease inhibitor drug after identifying genotypic resistance were associated with reduced risk. Detection of three CWR was also significantly associated with higher risk of AIDS-related death and new AIDS event/death.
Even in the late era of highly effective antiretroviral treatments, detection of CWR, particularly if extended to all three drug classes is related to poorer clinical outcome and represents a risk-marker of disease progression and death.

  • Source
    • "Increasing number of HIV-infected patients harbor multi-resistant strains [Sabin et al., 2005]. Given that multi-resistance is associated with an increased morbidity [Zaccarelli et al., 2005], such patients are often hospitalized and may be source-patients in occupational exposures [Beltrami et al., 2003]. The most recent cases of post-exposure prophylaxis failure occurred after exposure to source-patients harboring resistant HIV strains [Hawkins et al., 2001; Beltrami et al., 2002]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: We report the case of a health care worker who received a post-exposure prophylaxis including an investigational drug, maraviroc, after a needle stick percutaneous injury to an HIV-infected patient with late-stage disease and harboring a multi-drug resistant virus. Post-exposure prophylaxis including maraviroc was pursued for a total of 28 days, with a weekly clinical and biological evaluation. Post-exposure prophylaxis was well tolerated, with no increase in liver function tests. The health care worker remained HIV-negative after a 6-month follow-up.
    Journal of Medical Virology 01/2008; 80(1):9-10. DOI:10.1002/jmv.21000 · 2.22 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In the last years there has been a rapid development of probability models and statistical analysis for technological and medical survival data. The proportional hazard model formulated by Cox (1972) has rapidly become one of the most widely used methods for the analysis of clinical data, turning into a very powerful tool that has served to generalize the use of the analysis of survival This model is particulary useful examining treatment comparisons based on the times to some event while adjusting for the effects of concomitant variables and easily adapts to the incomplete data which are frequent in medical research. We work with censored data on the right, for which we used the statistical package S-Plus. In this paper we applied the Coxs proportional hazard model in a study of 1366 women infected with AIDS in Andalusia (Spain) between the years 1982 and 2001 focusing on the following variables: age, time of diagnosis, province of residence and level of transmission. The main result has been an increase in the survival of women with the introduction of the "Antiretroviral Therapy Very Active" in 1996, women diagnosed in the period 1993-1995 have an irrigation die 2.3 times greater than that diagnosed after 1996. As for age, women 35 years and older have a risk of death 1.8 times higher than in women under 30. The province with the largest survival is Grenada. We have not found any differences in the category of transmission. The data has been provided by the Andalusian Registry of AIDS.
  • 01/1970: pages 231-261;
Show more