C. Fabre-Colin

Publications (2)17.39 Total impact

• Article: Trends in virological and clinical outcomes in individuals with HIV-1 infection and virological failure of drugs from three antiretroviral drug classes: a cohort study

  D. Costagliola, R. K. Lodwick, B. Ledergerber, C. Torti, A. van Sighem, D. Podzamczer, A. Mocroft, M. Dorrucci, B. Masquelier, A. de Luca, [......], R. Zangerle, X. Duval, S. Perez Hoyos, L. Meyer, J. Ghosn, C. Fabre-Colin, Kjaer J., G. Chêne, J. Garup, A. Phillips
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  ABSTRACT: BACKGROUND: Limited treatment options have been available for people with HIV who have had virological failure of the three original classes of HIV antiretroviral drugs-so-called triple-class virological failure (TCVF). However, introduction of new drugs and drug classes might have improved outcomes. We aimed to assess trends in virological and clinical outcomes for individuals with TCVF in 2000-09. METHODS: In our cohort study, we analysed data for adults starting antiretroviral therapy from 1998 in cohorts participating in the PLATO II project, which is part of COHERE, a collaboration of European cohorts. TCVF was defined as virological failure to at least two nucleoside reverse transcriptase inhibitors, one non-nucleoside reverse-transcriptase inhibitor, and one ritonavir-boosted protease inhibitor, with virological failure of a drug defined as one viral-load measurement of greater than 500 copies per mL after at least 4 months of continuous use. We used multivariable generalised estimating equation logistic models and Poisson regression models to study trends in virological suppression and incidence of AIDS or death after TCVF. We adjusted for sex, transmission group, age, AIDS status, CD4 cell count, plasma viral loads at TCVF, achievement of virological response (<50 copies per mL), and number of drug failures before TCVF. FINDINGS: 28 of 33 cohorts in COHERE contributed data to the PLATO II project, of which four had no participants eligible for inclusion in this study. 2476 (3%) of 91 764 participants from the remaining 24 cohorts had TCVF and at least one viral load measurement in 2000-09. The proportion of patients with virological response after TCVF increased from 19.5% in 2000 to 57.9% in 2009 (adjusted p<0.0001). Incidence of AIDS decreased from 7.7 per 100 person-years in 2000-02 to 2.3 in 2008 and 1.2 in 2009 (adjusted p<0.0001). Mortality decreased from 4.0 per 100 person-years between 2000 and 2002 to 1.9 in 2007 and 1.4 in 2008 (unadjusted p=0.023), but the trend was not significant after adjustment (p=0.22). INTERPRETATION: A substantial improvement in viral load suppression and accompanying decrease in the rates of AIDS in people after extensive failure to drugs from the three original antiretroviral classes during 2000-09 was probably mainly driven by availability of newer drugs with better tolerability and ease of use and small cross-resistance profiles, suggesting the public health benefit of the introduction of new drugs. FUNDING: UK Medical Research Council.
  The Lancet Infectious Diseases 01/2012; 12(2):119-127. · 17.39 Impact Factor
• Article: Triple-class virologic failure in HIV-infected patients undergoing antiretroviral therapy for up to 10 years

  R. Lodwick, D. Costagliola, P. Reiss, C. Torti, R. Teira, M. Dorrucci, B. Ledergerber, A. Mocroft, D. Podzamczer, A. Cozzi-Lepri, [......], S. Lo Caputo, H. Gunthard, R. Paredes, A. De Luca, D. Paraskevis, C. Fabre-Colin, J. Kjaer, G. Chene, J. D. Lundgren, A. N. Phillips
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  ABSTRACT: BACKGROUND: Life expectancy of people with human immunodeficiency virus (HIV) is now estimated to approach that of the general population in some successfully treated subgroups. However, to attain these life expectancies, viral suppression must be maintained for decades. METHODS: We studied the rate of triple-class virologic failure (TCVF) in patients within the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) who started antiretroviral therapy (ART) that included a nonnucleoside reverse-transcriptase inhibitor (NNRTI) or a ritonavir-boosted protease inhibitor (PI/r) from 1998 onwards. We also focused on TCVF in patients who started a PI/r-containing regimen after a first-line NNRTI-containing regimen failed. RESULTS: Of 45 937 patients followed up for a median (interquartile range) of 3.0 (1.5-5.0) years, 980 developed TCVF (2.1%). By 5 and 9 years after starting ART, an estimated 3.4% (95% confidence interval [CI], 3.1%-3.6%) and 8.6% (95% CI, 7.5%-9.8%) of patients, respectively, had developed TCVF. The incidence of TCVF rose during the first 3 to 4 years on ART but plateaued thereafter. There was no significant difference in the risk of TCVF according to whether the initial regimen was NNRTI or PI/r based (P = .11). By 5 years after starting a PI/r regimen as second-line therapy, 46% of patients had developed TCVF. CONCLUSIONS: The rate of virologic failure of the 3 original drug classes is low, but not negligible, and does not appear to diminish over time from starting ART. If this trend continues, many patients are likely to need newer drugs to maintain viral suppression. The rate of TCVF from the start of a PI/r regimen after NNRTI failure provides a comparator for studies of response to second-line regimens in resource-limited settings.
  Arch Intern Med. 01/2010; 170(5):410-9.