Calendar time trends in the incidence and prevalence of triple-class virologic failure in antiretroviral drug-experienced people with HIV in Europe.
ABSTRACT Despite the increasing success of antiretroviral therapy (ART), virologic failure of the 3 original classes [triple-class virologic failure, (TCVF)] still develops in a small minority of patients who started therapy in the triple combination ART era. Trends in the incidence and prevalence of TCVF over calendar time have not been fully characterised in recent years.
Calendar time trends in the incidence and prevalence of TCVF from 2000 to 2009 were assessed in patients who started ART from January 1, 1998, and were followed within the Collaboration of Observational HIV Epidemiological Research Europe (COHERE).
Of 91,764 patients followed for a median (interquartile range) of 4.1 (2.0-7.1) years, 2722 (3.0%) developed TCVF. The incidence of TCVF increased from 3.9 per 1000 person-years of follow-up [95% confidence interval (CI): 3.7 to 4.1] in 2000 to 8.8 per 1000 person-years of follow-up (95% CI: 8.5 to 9.0) in 2005, but then declined to 5.8 per 1000 person-years of follow-up (95% CI: 5.6 to 6.1) by 2009. The prevalence of TCVF was 0.3% (95% CI: 0.27% to 0.42%) at December 31, 2000, and then increased to 2.4% (95% CI: 2.24% to 2.50%) by the end of 2005. However, since 2005, TCVF prevalence seems to have stabilized and has remained below 3%.
The prevalence of TCVF in people who started ART after 1998 has stabilized since around 2005, which most likely results from the decline in incidence of TCVF from this date. The introduction of improved regimens and better overall HIV care is likely to have contributed to these trends. Despite this progress, calendar trends should continue to be monitored in the long term.
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ABSTRACT: Background People who inject drugs (PWID) are a key population affected by HIV. We assessed the effectiveness of HIV treatment among a clinical cohort of people living with HIV (PLHIV) diagnosed and referred for community-based antiretroviral therapy (ART) in Victoria, Australia.MethodsHIV notification data from a central statewide registry were matched with HIV clinical data from two large HIV treatment centers in Melbourne. We used survival analysis and Cox proportional hazard models to estimate time to AIDS and death for PWID in HIV treatment, compared with non-injectors, in the period 1996 ¿ 2008.ResultsOf the 871 individuals, 93 (10.8%) had injecting as an exposure category and 671 (86%) had ever commenced ART. Adjusted analysis showed younger age, high initial CD4 cell count (>500 cells/mm3) or ever having a CD4 cell count >500/mm3, and more recent calendar year of ART commencement were all associated with reduced hazards for AIDS and death, while older age, low initial CD4 cell count (<200/mm3), ever having a CD4 count <200/mm3 (before or during treatment) and high initial viral load (>5 log10) were associated with increased risk of AIDS and death. PWID were no more likely to experience AIDS (HR 0.98[0.54 ¿ 1.80]) or death (HR 0.78 [0.18 ¿ 3.42]) than non-injectors.Conclusion Survival of HIV-infected PWID on HIV treatment was equivalent to non-injectors. CD4 cell count, initial viral load, calendar year of commencing ART and age are more important determinants of AIDS and mortality than injecting status for in-treatment PLHIV in Victoria, Australia.BMC Infectious Diseases 12/2014; 14(1):707. DOI:10.1186/s12879-014-0707-9 · 2.56 Impact Factor
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ABSTRACT: Background Highly active antiretroviral therapy (HAART) has reduced morbidity and mortality in patients infected with human immunodeficiency virus (HIV). Studies have documented high interindividual variability in the pharmacokinetics of antiretroviral drugs, which may impair the success of HAART if not managed properly. Therapeutic drug monitoring (TDM) is a useful diagnostic tool that helps clinicians to optimize drug doses so that drug concentrations associated with the highest therapeutic efficacy are obtained with a reduced risk of concentration-dependent adverse effects. The aim of this study was to assess whether use of TDM improves clinical outcomes and cost of illness. Methods A retrospective cohort study was conducted at L Sacco University Hospital in Milan, Italy, in HIV-infected patients aged ≥18 years with at least one prescription of antiretroviral drugs for which TDM was applied. The inclusion period was from January 2010 to December 2011, with a follow-up period of up to 12 months. Laboratory and administrative databases were analyzed and matched with each other. Results The cohort consisted of 5,347 patients (3,861 males and 1,486 females) of mean age 43.9±12.5 years. We found that TDM had been used in 143 of these patients, among whom adherence with therapy was significantly higher than among those in whom TDM had not been used (94% versus 78%). In TDM-controlled patients, the mean length of HIV-related hospitalization stay and mean cost of hospitalization were significantly reduced with respect to those observed in the group in which TDM had not been used (7.21 days versus 29.47 days and €293 versus €688, respectively). Conclusion Inclusion of TDM as part of routine clinical optimization of drug dosing in HIV-infected patients is associated with higher adherence to therapy, reduced length of hospitalization stay, and reduced cost of illness.ClinicoEconomics and Outcomes Research 07/2014; 6:341-8. DOI:10.2147/CEOR.S58036
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ABSTRACT: Retrovirus population diversity within infected hosts is commonly high due in part to elevated rates of replication, mutation, and recombination. This high genetic diversity often complicates the development of effective diagnostics, vaccines, and antiviral drugs. This review highlights the diverse vectors and approaches that have been used to examine mutation and recombination in retroviruses. Retroviral vectors for these purposes can broadly be divided into two categories: those that utilize reporter genes as mutation or recombination targets and those that utilize viral genes as targets of mutation or recombination. Reporter gene vectors greatly facilitate the detection, quantification, and characterization of mutants and/or recombinants, but may not fully recapitulate the patterns of mutagenesis or recombination observed in native viral gene sequences. In contrast, the detection of mutations or recombination events directly in viral genes is more biologically relevant but also typically more challenging and inefficient. We will highlight the advantages and disadvantages of the various vectors and approaches used as well as propose ways in which they could be improved.Viruses 09/2014; 6(9):3612-3642. DOI:10.3390/v6093612 · 3.28 Impact Factor