Michael Norton

Université de Montpellier 1, Montpelhièr, Languedoc-Roussillon, France

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Publications (18)56.77 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Increased access to successful antiretroviral therapy (ART) is necessary in order to achieve an AIDS-free generation. Importantly, slightly over half of the people living with HIV are women. Small studies have described many barriers to accessing treatment and care among women living with HIV. This cross-sectional, non-interventional, epidemiological study assessed the prevalence of barriers to accessing care for women living with HIV across 27 countries, divided into four global regions. HIV-positive women attending routine clinical visits were offered the opportunity to participate in the study. Data describing the study sites and demographic characteristics of the participating women were collected. Participating women filled out questionnaires including the Barriers to Care Scale (BACS) questionnaire, on which they reported the extent to which they found each of the 12 potential barriers to accessing health care problematic. A total of 1931 women living with HIV were included in the study: 760 from Western Europe and Canada (WEC), 532 from Central and Eastern Europe (CEE), 519 from Latin America (LA), and 120 from China. The mean age of participating women was 40.1 ± 11.4 years. A total of 88.2% were currently taking ART. A total of 81.8% obtained HIV treatment under a government health plan. The most prevalent barrier to care was community HIV/AIDS stigma. Community HIV/AIDS knowledge, lack of supportive/understanding work environments, lack of employment opportunities, and personal financial resources were also highly prevalent barriers to accessing care. These findings indicate that, more than 30 years after the start of the AIDS epidemic, stigma is still a major issue for women living with HIV. Continued efforts are needed to improve community education on HIV/AIDS in order to maximize access to health care among women living with HIV.
    AIDS Care 07/2015; DOI:10.1080/09540121.2015.1046416 · 1.60 Impact Factor
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    ABSTRACT: Inhibition of the cytochrome p450 3A4 enzyme system leads to increases in plasma concentrations of coadministered antiretroviral agents - a concept known as pharmacokinetic boosting. Ritonavir and cobicistat are potent inhibitors of cytochrome p450 3A4. Ritonavir was initially developed as an HIV protease inhibitor, but is currently used primarily as a pharmacokinetic boosting agent for other HIV and hepatitis C protease inhibitors. Cobicistat is a boosting agent for the integrase inhibitor elvitegravir and the protease inhibitors atazanavir and darunavir. Phase III data showed that atazanavir + cobicistat + tenofovir/emtricitabine had non-inferior efficacy and resulted in similar CD4 T-cell count increases to atazanavir + ritonavir + tenofovir/emtricitabine. The tolerability, gastrointestinal, and lipid profile of the cobicistat-containing regimen was comparable with the ritonavir-containing regimen. Primary HIV protease resistance mutations were not selected in either ritonavir or cobicistat arm virologic failures. Cobicistat-containing regimens have consistently shown higher serum creatinine increases and creatinine clearance decreases compared with ritonavir, and accurate assessment of glomerular filtration in the presence of cobicistat could only be made by using exogenous markers such as iohexol. Drugs contraindicated with cobicistat are consistent with those contraindicated with ritonavir-containing protease inhibitor regimens with respect to cytochrome p450 3A interactions. Information in this review may help clinicians assess the benefits and limitations of currently available pharmacokinetic enhancers when selecting the most appropriate treatment for their patients.
    AIDS reviews 01/2015; 17(1). · 3.79 Impact Factor
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    ABSTRACT: Introduction During pregnancy, LPV/r is a common anchor drug employed to treat the mother's HIV-1 infection in addition to reducing the risk of mother-to-child transmission (MTCT). The National Study of HIV in Pregnancy and Childhood (NSHPC) conducts a comprehensive population-based surveillance of HIV infection in pregnant women exposed to antiretroviral therapy (ART) in the UK and Ireland; in 2003–2012 over a third of pregnancies reported to the NSHPC involved exposure to LPV/r. Methods We undertook a retrospective were descriptive analysis of individual NSHPC patient data, using pregnancy as the unit of observation. Clinical outcomes for pregnancies reported by June 2013, where women were exposed to LPV/r and due to deliver between January 2003 and December 2012, are described. Results A total of 4864 LPV/r exposed pregnancies in 4118 women were identified. These resulted in 4702 deliveries with 4759 live and 46 stillborn infants. Seventy five percent of women were born in sub-Saharan Africa, 13% in the UK or Ireland. Median maternal age at conception was 30 years. Nine hundred and eighty (20%) pregnancies were conceived while taking LPV/r, with a median duration of LPV/r exposure of 270 days. A total of 3884 (80%) pregnancies initiated LPV/r after conception, with a median duration of LPV/r exposure of 107 days. Viral load (VL) close to delivery was available for 4083/4702 (87%) deliveries, with VL <50 c/mL in 73% and <1000 c/mL in 94% of women. VL by timing of LPV/r initiation is shown in Table 1. Sixty three percent of deliveries were by C-section, of which 62% were classified as elective and 38% as emergency. Among singleton liveborn infants, 13% were born prior to 37 weeks gestation (2.5% <32 weeks) and 15% had birth weight <2500 g (2.3% <1500 g). HIV infection status was available for 4039 (89%) singleton infants. For the periods 2003–2007 and 2008–2012, MTCT rates were 1.1% (95% CI 0.6–1.6) and 0.5% (95% CI 0.2–0.8) respectively. Hundred and thirty four live born children (2.8%) had at least one congenital abnormality reported. Conclusions In the NSHPC database, in women exposed to LPV/r during pregnancy in the UK and Ireland, MTCT rates are low and continue to decline, and are similar to rates in the entire NSHPC cohort of women with diagnosed HIV [1]. The congenital abnormality rate is comparable with that reported for the uninfected population in this geographic region.
    Journal of the International AIDS Society 11/2014; 17(4 Suppl 3):19613. DOI:10.7448/IAS.17.4.19613 · 5.09 Impact Factor
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    ABSTRACT: Aim: To assess renal function changes among 172 treatment-naive subjects treated with lopinavir/ritonavir (LPV/r) plus raltegravir (RAL) or LPV/r plus tenofovir/emtricitabine in the PROGRESS study, a prospective, randomized controlled trial. Patients & methods: Serum creatinine, creatinine clearance and chronic kidney disease category were compared between groups. Results: Mean change from baseline to week 96 in creatinine clearance was smaller with LPV/r plus RAL versus LPV/r plus tenofovir/emtricitabine (-1.4 vs -7.3 ml/min; p = 0.035). Chronic kidney disease category improvement was more frequent and the mean increase in serum creatinine was smaller for the LPV/r plus RAL group. Differences in estimated renal function were also detected when the analysis was performed according to baseline demographics. Conclusion: Smaller renal function declines were observed with LPV/r plus RAL. The results from this study warrant further evaluation of the renal safety profile of nucleotide reverse transcriptase inhibitor-sparing regimens.
    Future Virology 08/2014; 9(8-8):707-714. DOI:10.2217/fvl.14.55 · 1.01 Impact Factor
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    ABSTRACT: CRANIum, a cross-sectional epidemiology study in Western Europe and Canada, was conducted to describe and compare the prevalence of a positive screen for neurocognitive impairment (NCI), depressive symptoms, and anxiety in an HIV-positive population either receiving combination antiretroviral therapy (cART) or who were naive to antiretroviral therapy (ART). HIV-positive patients ≥18 years of age attending a routine medical follow-up visit and able to complete the designated screening tools were eligible for study inclusion. The Brief Neurocognitive Screen was used to assess NCI; depressive and anxiety symptoms were assessed using the Hospital Anxiety and Depression Scale. The evaluable patient population (N = 2863) included 1766 men (61.7%) and 1096 (38.3%) women. A total of 1969 patients were cART-experienced (68.8%), and 894 were ART-naive (31.2%). A positive screen for NCI was found in 41.5% of patients (cART-experienced, 42.5%; ART-naive, 39.4%; p = 0.12). A positive screen for depressive symptoms was found in 15.7% of patients (cART-experienced, 16.8%; ART-naive, 13.3%; p = 0.01), whereas 33.3% of patients screened positive for anxiety (cART-experienced, 33.5%; ART-naive, 32.8%; p = 0.71). A greater percentage of women compared with men screened positive for NCI (51.78% vs. 35.1%; p < 0.0001) and depressive symptoms (17.9% vs. 14.3%; p = 0.01). These data suggest that neurocognitive and mood disorders remain highly prevalent in HIV-infected patients. Regular mental health screening in this population is warranted.
    AIDS Care 07/2014; 26(12):1-7. DOI:10.1080/09540121.2014.936813 · 1.60 Impact Factor
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    ABSTRACT: Aim: Data describing the safety and efficacy of antiretroviral therapy (ART) in HIV-infected patients aged 50 years are limited. We evaluated the effect of age on safety, efficacy and tolerability in patients aged <50 and 50 years receiving lopinavir/ritonavir (LPV/r)-containing ART. Methods: End points from AbbVie Inc. (IL, USA) or AIDS Clinical Trials Group randomized clinical trials in adults using LPV/r 800/200 mg/day as part of a three-drug regimen (follow-up 48 weeks) were evaluated using a random-effects meta-analysis (virologic efficacy; intent-to-treat; noncompleter = failure) or pooled data (other end points). Results: A total of 2608 patients (2294.3 patient-years of follow-up) from ten trials were included: 2248 patients (86.2%) <50 years of age and 360 (13.8%) 50 years of age. Demographics and baseline characteristics were similar between age groups. At week 48, 64.9 and 67.8% of patients <50 and 50 years, respectively, had plasma HIV-1 RNA <50 copies/ml (random effects meta-analysis p = 0.992). Mean change from baseline in CD4(+) T-cell count was +193.9 and +163.5 cells/l (<50 and 50 years, respectively; p < 0.001). Smaller proportions of patients <50 years of age discontinued due to adverse events (AEs)/HIV-related events (4.9 vs 9.4%; p = 0.001) and reported moderate-to-severe treatment-related AEs (30.5 vs 36.4%; p = 0.027) compared with patients 50 years of age. Conclusion: This analysis suggests LPV/r-anchored three-drug therapy in patients 50 years of age leads to comparable rates of virologic suppression, with a smaller increase in absolute CD4(+) T cells and increased AEs, including discontinuations associated with AEs compared with patients <50 years of age.
    Future Virology 04/2014; 9(4):351-362. DOI:10.2217/fvl.14.18 · 1.01 Impact Factor
  • R D'Amico · C Wegzyn · W Richter · C Lin · J Beron · Y Hu · L Fredrick · B Saget · M Guion · M Norton
    Journal of the International AIDS Society 06/2013; 16(Suppl 1). DOI:10.7448/IAS.16.2.18655 · 5.09 Impact Factor
  • A Hermes · L Fredrick · M Martinez · R Rode · M Pasley · M Norton · A Nilius
    Journal of the International AIDS Society 06/2013; 16(Suppl 1). DOI:10.7448/IAS.16.2.18652 · 5.09 Impact Factor
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    ABSTRACT: Purpose of the study: The prevalence of neurocognitive impairment (NCI) in people living with HIV has previously been reported between 20-50%, with prevalence rates of depression reported between 12-71%. The primary objective of the CRANIum study was to describe the prevalence of a positive screen for NCI and depression/anxiety in an HIV-1-infected adult population, comparing ARV-naïve and -experienced patients. Here we present an ethnicity analysis of the CRANIum data. Methods: The study was an epidemiologic, cross-sectional study that included HIV-1-infected patients >18 years old attending a routine clinic visit. One-third of patients were ART-naïve, one-third on a PI/r- and one-third on a NNRTI-based regimen. The Brief Neurocognitive Screen (BNCS) was used to screen for NCI. It consists of the Digit Symbol and Trailmaking A and B tests. A standard deviation of >1 on 2 tests or >2 on 1 test was considered a positive screen for NCI. The Hospital Anxiety and Depression Scale (HADS) was used to screen for anxiety (HADS-A) and depression (HADS-D). HADS is self-administered and consists of 14 items (7 HADS-A, 7 HADS-D) scored between 0 to 3. A score of ≥8 was considered as a positive screen for either condition. Summary of results: 2859 evaluable patients were included from 15 countries. Baseline characteristics are shown in table 1 (*p < 0.05 as compared with Caucasian group). Overall, 41.4% of patients had a positive screen for NCI, 33.3% for anxiety and 15.7% for depression. Results by ethnicity are shown in figure 1. Conclusions: In this large epidemiologic study, the overall prevalence of a positive screen for NCI was high. In particular, the rate in black patients was nearly double that of the overall study population. This finding needs to be interpreted in light of differences in demographics and disease characteristics between ethnic groups. The overall prevalence of a positive screen for depression in HIV-infected patients was nearly double what has previously been reported in the non-HIV-infected population in Europe when utilizing a similar screening tool, with no significant differences between identified ethnic groups. These results support a strategy of regular screening for, and clinical management of NCI, depression, and anxiety in all HIV-infected patients, with specific focus on NCI in the black population.
    Journal of the International AIDS Society 11/2012; 15(6):18276. DOI:10.7448/IAS.15.6.18276 · 5.09 Impact Factor
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    ABSTRACT: Purpose: Women comprise ≯50% of HIV-infected patients, yet safety, tolerability, and efficacy data in women taking antiretrovirals (ARVs) are limited. Lopinavir/ ritonavir (LPV/r)-anchored regimens are globally the most widely prescribed HIV-1 protease inhibitor regimens. The objective was to investigate the safety and efficacy of LPV/r-based therapy in women. Methods: A database query yielded all available data in HIV-1-infected subjects receiving LPV/r-based triple-ARV regimens from randomized clinical trials lasting ≥48 weeks from Abbott or Abbott-supported AIDS Clinical Trials Group studies. Efficacy (HIV-1 RNA levels, CD4+ T-cell counts) and safety and tolerability (treatment discontinuation, treatment-related adverse events [AE], and clinical laboratory abnormalities) at 48 weeks were assessed for total women, women by age (≥50, <50 years) and body mass index (BMI; <25, ≥25 to <30, ≥30 kg/m2), and sex. Results: Nine hundred ninety-two women initiated LPV/r-based therapy (of whom 79.2% were ARV-naïve), with 83.6% completing 48 weeks of treatment. There were 75.5% of women who achieved a threshold of HIV RNA <400 copies/mL by intent-to-treat, non-completer equals failure (ITT, NC = F) analysis, with a mean ± SE CD4+ T-cell count increase of 191.6 ± 4.92 cells/mm3 from baseline. Women aged ≥50 versus <50 years had higher incidence of moderate-to-severe treatment-related AEs and certain laboratory abnormalities, better virologic response (HIV RNA <400 copies/mL by ITT, NC = F), similar immunologic responses, and similar overall incidence of treatment discontinuations. Higher incidences of certain moderate-to-severe treatment-related AEs and laboratory abnormalities occurred in women with BMI ≥30 kg/m2; however, no effect of BMI on efficacy or discontinuation was observed. Conclusions: LPV/r-based regimens were efficacious and well-tolerated in women without marked differences based on age and BMI categories evaluated.
    HIV Clinical Trials 11/2012; 13(6):308-23. DOI:10.1310/hct1306-308 · 2.63 Impact Factor
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    ABSTRACT: Abstract Alternative combinations of antiretrovirals (ARVs) are desired to increase treatment options for HIV-infected patients. PROGRESS was a randomized, open-label, 96-week pilot study comparing a regimen of lopinavir/ritonavir (LPV/r) 400/100 mg twice daily in combination with either raltegravir (RAL) 400 mg twice daily or tenofovir/emtricitabine (TDF/FTC) 300/200 mg once daily in ARV-naive adults. A total of 206 subjects were randomized and treated (LPV/r+RAL, N=101; LPV/r+TDF/FTC, N=105). Demographics and baseline characteristics were similar across treatment groups. At 96 weeks, 66.3% of subjects receiving LPV/r+RAL and 68.6% of subjects receiving LPV/r+TDF/FTC were responders (plasma HIV-1 RNA levels<40 copies/ml) by the FDA time to loss of virologic response (FDA-TLOVR) algorithm (p=0.767). Mean CD4(+) T cell increases through 96 weeks were similar between treatment groups (LPV/r+RAL=281 cells/mm(3), LPV/r+TDF/FTC=296 cells/mm(3), p=0.598). Safety and tolerability were generally similar between groups. The LPV/r+RAL regimen resulted in greater increases in peripheral fat, but not trunk fat, compared with LPV/r+TDF/FTC. There was a statistically significantly greater mean reduction in estimated glomerular filtration rate from baseline to week 96 in the LPV/r+TDF/FTC group compared with the LPV/r+RAL group (-7.33 ml/min vs. -1.43 ml/min; p=0.035). The LPV/r+TDF/FTC group had a statistically significant (p<0.001) mean percent decrease from baseline to week 96 in bone mineral density, which was significantly different from the mean percent change in the LPV/r+RAL group (-2.48% vs. +0.68%, p<0.001). These efficacy and safety observations support further evaluation of the LPV/r+RAL regimen.
    AIDS research and human retroviruses 06/2012; 29(2). DOI:10.1089/AID.2011.0275 · 2.33 Impact Factor
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    ABSTRACT: There is growing interest in studying age-related diseases, such as coronary artery disease (CAD) and resulting myocardial infarction (MI) in HIV-infected patients. While some cohort studies indicate that several antiretrovirals (ARVs), including the protease inhibitor lopinavir/ ritonavir (LPV/r), are associated with an increased relative risk (RR) of MI, other studies show a reduction of MI and CAD in subjects taking ARVs when compared with HIV+ patients not taking ARV therapy. This manuscript reviews data from Abbott-sponsored clinical trials and pharmacovigilance reporting system. A systematic search was performed to retrieve cases of MI and CAD in Abbott’s clinical trial and pharmacovigilance safety databases. The rates of MI and CAD, and risk factors for the events were reviewed in detail. The rate of MI and CAD per 1,000 patient treatment years (PTY) was 1.24 (95% CI = 0.40 - 2.90) and 2.74 (95% CI = 1.37 - 4.90), respectively, for subjects taking LPV/r during clinical trials. The frequency of pharmacovigilance reports of MI and CAD were 2.9 per 100,000 PTY and 3.6 per 100,000 PTY, respectively. Most subjects who had MI and CAD events had multiple baseline risk factors. Relatively few subjects experienced MI or CAD during Abbott-sponsored clinical trials of LPV/r. Analysis of clinical trial and pharmacovigilance data did not indicate an increased risk of MI or CAD associated with LPV/r compared with the general population. In general, the subjects that experienced MI or CAD had known traditional risk factors suggesting that addressing modifiable risk factors could decrease the risk of MI or CAD. ARVs have not been thoroughly studied in subjects at high risk for MI and CAD, and further studies of this population could identify whether starting ARVs affects the incidences of cardic events in subjects with many traditional risk factors
    International journal of clinical pharmacology and therapeutics 04/2012; 50(6):391-402. DOI:10.5414/CP201606 · 1.22 Impact Factor
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    ABSTRACT: Background Antiretroviral therapy is associated with adverse events (AEs). The most frequently reported AE associated with lopinavir/ritonavir (LPV/r) containing regimens is diarrhea. The objective of this meta-analysis is to describe the incidence, prevalence, and duration of diarrhea in individuals taking LPV/r. Methods This is a meta-analysis of Abbott-conducted clinical trials. Inclusion criteria included prospective randomized clinical trials with the LPV/r tablet formulation and had AE data (moderate/severe diarrhea) available through 48 weeks of treatment. Results Three trials (total 1469 participants) met the inclusion criteria. In all, 11.2% of participants reported moderate/severe diarrhea by week 8, with median time to resolution of 7.4 weeks. The overall 48-week incidence of moderate/severe diarrhea was 15.5%. The discontinuation rate due to moderate/severe diarrhea was 1.3%. Conclusions Moderate/severe diarrhea occurred in less than 1 in 6 participants taking LPV/r, typically started in the first 8 weeks of treatment and infrequently resulted in premature discontinuation.
    Journal of the International Association of Physicians in AIDS Care (JIAPAC) 04/2012; 11(4):252-9. DOI:10.1177/1545109712442984
  • Future Virology 01/2012; 7(1):103-113. DOI:10.2217/fvl.11.127 · 1.01 Impact Factor
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    ABSTRACT: Patterns of HIV-1 protease inhibitor (PI) resistance-associated mutations (RAMs) and effects on PI susceptibility associated with the L76V mutation were studied in a large database. Of 20,501 sequences with ≥1 PI RAM, 3.2% contained L76V; L76V was alone in 0.04%. Common partner mutations included M46I, I54V, V82A, I84V, and L90M. L76V was associated with a 2- to 6-fold decrease in susceptibility to lopinavir, darunavir, amprenavir, and indinavir and a 7- to 8-fold increase in susceptibility to atazanavir and saquinavir.
    Antimicrobial Agents and Chemotherapy 11/2010; 54(11):4903-6. DOI:10.1128/AAC.00906-10 · 4.48 Impact Factor
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    JL Casado · L Griffa · E Cabrero · A Burgos · M Norton
    Journal of the International AIDS Society 01/2008; 11:1-1. DOI:10.1186/1758-2652-11-S1-P80 · 5.09 Impact Factor
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    ABSTRACT: Prior attempts to reduce the number of drugs needed to maintain viral suppression in patients with suppressed HIV replication while receiving three antiretroviral drugs have been unsuccessful. In 205 patients with suppressed HIV replication on lopinavir-ritonavir and two nucleosides, this randomized, open-label, non-inferiority clinical trial compared the strategies of continuation of triple therapy versus lopinavir-ritonavir monotherapy followed by reinduction with two nucleosides if virological rebound occurred without genotypic resistance to lopinavir-ritonavir. The primary endpoint was proportion of patients without therapeutic failure, defined as confirmed HIV RNA higher than 500 copies/mL (with exclusion of patients receiving monotherapy who resuppressed to < 50 copies/mL after resuming baseline nucleosides), or loss to follow-up, or change of randomized therapy other than reinduction. At week 48, the percentage of patients without therapeutic failure was 94% in the monotherapy group versus 90% in the triple therapy group (difference,-4%; upper limit of 95% confidence interval for difference, 3.4%). The percentage of patients with HIV RNA 50 copies/mL at 48 weeks by intention-to-treat, missing data or reinductions considered as failures, were 85% in the monotherapy group versus 90% in the triple therapy group (P = 0.31; 95% upper limit of 95% confidence interval for difference, 14%). In this trial, 48 weeks of lopinavir-ritonavir monotherapy with reintroduction of nucleosides as needed was non-inferior to continuation of two nucleosides and lopinavir-ritonavir in patients with prior stable suppression. However, episodes of low level viremia were more common in patients receiving monotherapy.
    AIDS (London, England) 01/2008; 22(2):F1-9. DOI:10.1097/QAD.0b013e3282f4243b · 5.55 Impact Factor
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    Journal of the International AIDS Society 01/2008; 11(Suppl 1). DOI:10.1186/1758-2652-11-S1-P308 · 5.09 Impact Factor

Publication Stats

130 Citations
56.77 Total Impact Points


  • 2012
    • Université de Montpellier 1
      Montpelhièr, Languedoc-Roussillon, France
  • 2010–2012
    • Abbott Laboratories
      • Abbott Laboratories
      North Chicago, IL, United States
  • 2008
    • Complutense University of Madrid
      Madrid, Madrid, Spain