Archive for October 14, 2009

Efavirenz: a decade of clinical experience in the treatment of HIV

Journal of Antimicrobial Chemotherapy  Nov. 2009  V.64  N.5  p.910-928

Reviews

Franco Maggiolo*

Division of Infectious Diseases, Ospedali Riuniti, Largo Barozzi 1, Bergamo 24128, Italy

Efavirenz, a non-nucleoside reverse transcriptase inhibitor, has been an important component of the treatment of HIV infection for 10 years and has contributed significantly to the evolution of highly active antiretroviral therapy (HAART). The efficacy of efavirenz has been established in numerous randomized trials and observational studies in HAART-naive patients, including those with advanced infection. In the ACTG A5142 study, efavirenz showed greater virological efficacy than the boosted protease inhibitor (PI), lopinavir. Efavirenz is more effective as a third agent than unboosted PIs or the nucleoside analogue abacavir. Some, but not all, studies have suggested that efavirenz (added to two nucleoside reverse transcriptase inhibitors) is more effective than nevirapine. Virological and immunological responses achieved with efavirenz-based HAART have been maintained for 7 years. Dosing convenience predicts adherence, and studies have demonstrated that patients can be switched from PI-based therapy to simplified, once-daily efavirenz-based regimens without losing virological control. The one-pill, once-daily formulation of efavirenz plus tenofovir and emtricitabine offers a particular advantage in this regard. Efavirenz also retains a role after failure of a first PI-based regimen. Efavirenz is generally well tolerated: rash and neuropsychiatric disturbances are the most notable adverse events. Neuropsychiatric disturbances generally develop early in treatment and they tend to resolve with continued administration, but they are persistent and troubling in a minority of patients. Efavirenz has less effect on plasma lipid profiles than some boosted PIs. Lipodystrophy can occur under treatment with efavirenz but it may be reduced if the concurrent use of thymidine analogues is avoided. Efavirenz resistance mutations (especially K103N) can be selected during long-term treatment, underscoring the importance of good adherence. Recent data have confirmed that efavirenz is a cost-effective option for first-line HAART. In light of these features, efavirenz retains a key role in HIV treatment strategies and is the first-line agent recommended in some guidelines.

abstract

http://jac.oxfordjournals.org/cgi/content/abstract/64/5/910

PDF

http://jac.oxfordjournals.org/cgi/reprint/64/5/910

October 14, 2009 at 6:07 pm Leave a comment

The safety of highly active antiretroviral therapy for the HIV-positive pregnant mother and her baby: is ‘the more the merrier’?

Journal of Antimicrobial Chemotherapy  Nov. 2009  V.64  N.5  p.895-900

F. Martin* and G. P. Taylor

Section of Infectious Diseases, Faculty of Medicine, Imperial College, Norfolk Place, London W2 1PG, UK

Highly active antiretroviral therapy (HAART) is frequently indicated for pregnant women both for maternal health and for prevention of mother-to-child HIV transmission, which can be reduced to <1%. Prospective data and large cohort studies have not found any evidence that antiretroviral therapy significantly increases the risk of congenital malformation. Nucleoside analogue reverse transcriptase inhibitors (NRTIs) are, to varying degrees, toxic to mitochondria, and molecular and clinical evidence of mitochondrial toxicity has been reported, albeit rarely, in NRTI-exposed but HIV-uninfected children. However, with NRTI-based fully suppressive antiretroviral therapy this effect was not seen. Although conflicting observational data have been reported, an increased risk of pre-term delivery with HAART compared with zidovudine monotherapy remains a concern.

abstract

http://jac.oxfordjournals.org/cgi/content/abstract/64/5/895

PDF

http://jac.oxfordjournals.org/cgi/reprint/64/5/895

October 14, 2009 at 6:06 pm Leave a comment

Swine flu and antibiotics

Journal of Antimicrobial Chemotherapy  Nov. 2009  V.64  N.5  p.889-894

Gavin D. Barlow* on behalf of the BSAC Council

Department of Infection & Tropical Medicine, Castle Hill Hospital, Hull & East Yorkshire Hospitals NHS Trust, Cottingham, East Yorkshire HU16 5JQ, UK

Health services worldwide are likely to be hard-pressed by swine flu-related illness in the months ahead. Secondary infections with Streptococcus pneumoniae, other streptococci (e.g. Streptococcus pyogenes), Haemophilus influenzae and Staphylococcus aureus are likely to be important causes of morbidity and mortality. The UK Department of Health recently published clinical pathways for the management of swine flu. Suggested severity criteria have not been validated in respiratory infection and are different from those previously published. Antibiotics are recommended for all patients assessed at hospital, regardless of severity of illness; cephalosporins or quinolones are suggested for inpatients with pneumonia. These recommendations will jeopardize recent decreases in Clostridium difficile-associated diarrhoea (CDAD) and methicillin-resistant S. aureus (MRSA) in UK hospitals. This article, written on behalf of the BSAC Council, considers these recommendations and provides alternative antibiotic regimens for a range of clinical scenarios.

abstract

http://jac.oxfordjournals.org/cgi/content/abstract/64/5/889

PDF

http://jac.oxfordjournals.org/cgi/reprint/64/5/889

October 14, 2009 at 6:05 pm Leave a comment

Antibiotic stewardship—more education and regulation not more availability?

Journal of Antimicrobial Chemotherapy  Nov. 2009  V.64  N.5  p.885-888

Matthew S. Dryden1,*, Jonathan Cooke2 and Peter Davey3

1 Department of Microbiology and Communicable Disease, Royal Hampshire County Hospital, Winchester SO22 5DG, UK 2 Manchester Academic Health Science Centre, University Hospital of South Manchester NHS Foundation Trust, Wythenshawe Hospital, Manchester M23 9LT, UK 3 Division of Clinical and Population Sciences and Education, Mackenzie Building, Kirsty Semple Way, Dundee DD2 4BF, UK

Antibiotics are overused across the world by prescription, self-medication or over the counter (OTC) availability. In the UK, the agenda to increase patient choice has stimulated a move towards greater availability of OTC antibiotics. This trend needs to be urgently reviewed and controlled. The Medicines and Healthcare products Regulatory Agency is currently reviewing applications for reclassification of trimethoprim and nitrofurantoin from prescription-only medicines to pharmacy availability or OTC. It is important that anti-infectives do not become more freely available. With the quantity of antibiotic use linked to antibiotic resistance, Society should seek to preserve the use of this irreplaceable resource by education and regulation.

abstract

http://jac.oxfordjournals.org/cgi/content/abstract/64/5/885

PDF

http://jac.oxfordjournals.org/cgi/reprint/64/5/885

October 14, 2009 at 6:04 pm Leave a comment


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