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Graeme Moyle

Publications and source records attributed to Graeme Moyle.

13 recordsLinked to original sources
PubMed2002

Overcoming obstacles to the success of protease inhibitors in highly active antiretroviral therapy regimens.

Success with current protease inhibitors (PIs) is limited by substantial variability in pharmacokinetics, onset of adverse metabolic effects that include sustained lipid elevations and insulin resistance, and increased risk of lipodystrophy. Additionally, poor adherence to the often complex regimens can lead to emergence of PI-resistant human immunodeficiency virus (HIV) variants and treatment failure. Boosting blood levels of current PIs through coadministration of ritonavir can improve the pharmacokinetic characteristics of these agents, increasing the chances of success, but often at the price of additional adverse effects. New PIs in development have the potential to overcome at least some of these obstacles. Tipranavir, mozenavir, and atazanavir have favorable and unique resistance profiles, making them potentially effective in new treatment strategies in both PI-naïve and PI-experienced patients. Atazanavir does not cause the lipid elevations seen with current PIs, and it may improve adherence through once-daily dosing.

Antiretroviral Therapy, Highly Active↗
PubMed2002

Time for T.

Explore the source record for details and available documents.

CD4 Lymphocyte Count↗
PubMed2002

Analysis of virological efficacy in trials of antiretroviral regimens: drawbacks of not including viral load measurements after premature discontinuation of therapy.

OBJECTIVES: To compare two analytic approaches to assess the virological effect of HAART according to the intention-to-treat (ITT) principle. MATERIAL: Data from 2318 patients enrolled in 10 randomised clinical trials (RCTs) and from 3091 patients followed in an observation cohort (EuroSIDA) starting their first HAART regimen. METHODS: Two classifications of defining virological response 48 weeks after starting the therapy to be evaluated were compared: 1) only patients remaining on the therapy and having a plasma viral load (pVL) below a given cut-off level at week 48 were classified as responders (ITT/s=f); and 2) patients with a pVL below a given cut-off at week 48 whether they remained on initial assigned therapy or switched therapy were responders (ITT/s incl). In both analyses, patients with missing data at week 48 were classified as failures (i.e., non-responders). RESULTS: According to ITT/s=f, 22-70% of the patients starting a HAART regimen in a RCT experienced a virological response at week 48. Only two RCTs had complete follow-up data (n=424): between 29 and 62% achieved a virological response at week 48 in the six treatment arms evaluated in the studies according to ITT/s=f, and 41-72% according to ITT/s incl. Among those who discontinued the therapy to be evaluated in these two trials, 13-45% (cohort: 39-74%) subsequently experienced a virological response at week 48. The subsequent response rates were associated with the reason for discontinuation (toxicity versus confirmed virological failure: 63 vs 33%), varied largely across regimens and were not associated with the discontinuation rate. CONCLUSIONS: Discontinuation of follow-up at switch from the therapy to be evaluated remains common in antiretroviral treatment trials, but leads to an imprecise and incomplete assessment of the intrinsic effect of a given regimen. Complete follow-up of all patients should be encouraged strongly as this will allow for several complementary analytic approaches and a focus on optimal treatment strategies rather than specific regimens.

Antiretroviral Therapy, Highly Active↗
PubMedDate not supplied

Anaemia in persons with HIV infection: prognostic marker and contributor to morbidity.

Human immunodeficiency virus (HIV)-infected patients experience a range of haematological complications including anaemia, neutropenia, lymphopenia and thrombocytopenia. Anaemia is a prognostic marker of future disease progression or death, independent of CD4 and viral load. Recovery from anaemia reduces the risk of disease progression to approximately the same level as seen among patients who have never had anaemia. Additionally, anaemia impacts a range of dimensions of quality of life, most commonly through fatigue. Anaemia can be caused by a range of mechanisms including infections, neoplasms, dietary deficiencies, blood loss and medication. Histologically, bone marrow hypoproliferation and dysplasia are the most commonly seen. Both AZT and d4T induce macrocytosis, however, AZT, but not d4T, has broader myelosuppressive effects both in vitro and in vivo. The management of anaemia typically includes correction of the underlying cause(s) and blood transfusion or erythropoietin. However, blood transfusions and iron supplementation may activate HIV expression and possibly worsen immunosuppression. Recombinant human erythropoietin (rHuEPO) is an effective means of improving haemoglobin and reducing transfusion requirements in patients who have low (< 500 IU/L) endogenous erythropoietin levels.

Anemia↗