Michael Norton

Abbott Laboratories, North Chicago, Illinois, United States

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Publications (5)10.25 Total impact

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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; · 2.18 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. · 1.20 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.
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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. · 4.57 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 13(6):308-23. · 2.30 Impact Factor