Antiretroviral therapy in pregnancy: local practice in East London, UK

A review of antiretroviral prescribing, mode of delivery and pregnancy outcome was performed to assess local practice against the new British HIV Association guidelines. HIV status prior to pregnancy, antiretroviral medication, viral load, mode of delivery and pregnancy outcome were determined in 95 pregnancies recorded between 2004 and 2006 via retrospective case-note review. In total, 75% (n=71) of pregnancies resulted in live births; 56% (n=53) of pregnancies occurred in women who knew they were HIV positive prior to the current pregnancy; 49% (n=26) of them conceived on antiretroviral therapy (ART). Use of protease-inhibitor-based ART and number of normalvaginal delivery increased and the use of zidovudine (AZT) monotherapy and emergency caesarean section (CS) fell during the study period. In conclusion, there was an increase in vaginal deliveries and a reduction in the number of emergency CSs between 2004 and 2006.     

HIV/HCV coinfection in clinical practice

Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) frequently co-exist due to shared routes of transmission. In the past, the impact of HCV on overall morbidity and mortality of coinfected patients was minimal due to the poor prognosis of HIV. However, since the introduction of highly active antiretroviral therapy (HAART), HCV has become a significant pathogen in this population. HIV clearly exacerbates HCV infection and accelerates progression to cirrhosis, end-stage liver disease, and hepatocellular carcinoma. There is debate over whether HCV influences the natural history of HIV. Given the high prevalence of coinfection and the accelerated liver damage, HCV treatment has become a priority in these patients. There are new data on pegylated interferon (PEG-IFN) and ribavirin (RBV) therapy for HCV in coinfected patients. The therapy is well tolerated and safe, although it appears to be slightly less effective than in monoinfected patients. The risk of HAART-related hepatotoxicity is greater in coinfected patients and therefore requires special consideration and close monitoring.     

Perioperative use of methotrexate--a survey of clinical practice in the UK

We have surveyed the use of methotrexate in the perioperative period in patients with rheumatoid arthritis (RA) undergoing surgery. A total of 200 consultant rheumatologists and 200 consultant orthopaedic surgeons in the UK were sent a postal questionnaire. Thirty-five per cent of rheumatologists and 46% of orthopaedic surgeons were concerned that the drug may increase the risk of post-operative complications, although significantly less 'always' stopped the drug around the time of surgery. There was great variation in the timing of stopping the drug with most stopping treatment within 2 weeks before surgery and restarting within 2 weeks after surgery. The majority of clinicians surveyed (70%) felt that national guidelines for the perioperative use of methotrexate would be helpful.      

HIV pharmacogenetics in clinical practice: recent achievements and future challenges

It has long been recognized that drug metabolism and drug toxicity may vary greatly between individuals, affecting both efficacy and toxicity. Pharmacogenetics could benefit HIV therapeutics because of the high prevalence of drug-related adverse events and the long term nature and complexity of combination therapy. In recent years a number of associations between human genetic variants and predisposition to drug toxicity and risk of virologic failure have been described. This review summarizes the existing literature on pharmacogenetic determinants of antiretroviral drug exposure, toxicity, and activity. Studies across the world have consistently demonstrated that HLA-B*5701 predicts the likelihood of hypersensitivity reactions to abacavir. As a consequence, pharmacogenetic screening for HLA-B*5701 has entered routine clinical practice and is recommended in most guidelines before starting an abacavir containing regimen. Moreover, prospective clinical trials and cohort studies have identified a number of associations between human genetic variants, drug metabolism and toxicity. These include nevirapine hypersensitivity and hepatotoxicity, efavirenz plasma levels and central nervous system side effects, indinavir- and atazanavir-associated hyperbilirubinemia, antiretroviral drug-associated peripheral neuropathy, lipodystrophy and hyperlipidaemia, NRTI-related pancreatitis, and tenofovir-associated renal proximal tubulopathy. Thus, pharmacogenetics is expected to play an important role in HIV treatment in the near future. The aim of the present paper is to provide HIV clinicians with a comprehensive review of recent achievements and future prospects for HIV pharmacogenetics.     

Technology insight: the evolution of tissue-engineered vascular grafts--from research to clinical practice

There is a considerable clinical need for alternatives to the autologous vein and artery tissues used for vascular reconstructive surgeries such as CABG, lower limb bypass, arteriovenous shunts and repair of congenital defects to the pulmonary outflow tract. So far, synthetic materials have not matched the efficacy of native tissues, particularly in small diameter applications. The development of cardiovascular tissue engineering introduced the possibility of a living, biological graft that might mimic the functional properties of native vessels. While academic research in the field of tissue engineering in general has been active, as yet there has been no clear example of clinical and commercial success. The recent transition of cell-based therapies from experimental to clinical use has, however, reinvigorated the field of cardiovascular tissue engineering. Here, we discuss the most promising approaches specific to tissue-engineered blood vessels and briefly introduce our recent clinical results. The unique regulatory, reimbursement and production challenges facing personalized medicine are also discussed.     

Developing clinical practice guidelines in HIV rehabilitation: process recommendations and guiding principles

Our purpose was to develop process recommendations and guiding principles for future clinical practice guidelines in HIV rehabilitation. We conducted a scoping study that included focus group and interview consultations with 28 participants including people living with HIV, researchers, clinicians, educators, and policy stakeholders with expertise in HIV and rehabilitation. We used qualitative content analysis techniques to identify emergent themes related to the development of clinical practice guidelines. Results included seven recommendations for the process of developing clinical practice guidelines in HIV rehabilitation that spanned areas of flexibility, scope, adopting existing evidence from concurrent health conditions, format, interprofessional approach to development and implementation, terminology, and knowledge translation. Three guiding principles emerged to inform the philosophical approach for guideline development. These findings serve as a foundation for the development of clinical practice guidelines in HIV rehabilitation to enhance the care and treatment of people living with HIV.     

The bleeding time: current practice in the UK

Summary. A questionnaire survey of current practice in the bleeding time test has been undertaken by the UK External Quality Assessment Scheme in blood coagulation. Completed returns have been received from 358 centres. Most centres (88.5%) perform bleeding times and of these the Ivy test is the most commonly performed. Only 13.6% perform the Duke method. Templates are used to control the procedure by approximately half of the hospitals. There is considerable variability in the type and depth of incision and interpretation of the endpoint. The upper limit of normality not unexpectedly differs considerably between the centres with both Ivy and Duke methods. The use of a commercial template method, ‘Simplate’, provides a measure of agreement amongst the group of hospitals using this instrument but it remains to be established whether this is the most reliable procedure. In the interim, gross discrepancies in technique or interpretation should be corrected in the light of the findings of the survey.     

The esophagus: New methodologies and discoveries lead to an evolution in clinical practice

New understandings of disease management often evolve from new discoveries or the development of new methodologies for investigation. This phenomenon is observed several times in the reviews featured in this issue. New tools in the investigation of esophageal physiology and in the treatment of esophageal disorders have led us to reappraise our understanding of this enigmatically complex organ.     

Management of HIV and pregnancy in England's North Thames Region 1999: a survey of practice in 21 hospitals

Objectives To ascertain current practices in the diagnosis and management of HIV and pregnancy in the North Thames Region.
Methods Postal survey using a self-completed questionnaire sent to the head of all of the Region's 34 units involved in the care of HIV. The survey asked questions on current policy around HIV and pregnancy in the HIV units and associated antenatal clinics and was linked to a case-note survey of pregnant, HIV-positive women in the last 2 years.
Results Over 50% of the responding antenatal units recommended the HIV test by March 1999. Most HIV units were offering a range of antiretroviral regimens in pregnancy, although a minority (33%) did not offer triple therapy. Elective Caesarean section was the recommended mode of delivery for most women (90%) irrespective of drug therapy or viral load. Most infants were being tested for HIV infection by a combination of PCR, viral culture and antibody testing to 18 months of age. All the infants (19) followed to 6 months of age in the case-note survey were PCR negative. Reporting rates to the National Survey of HIV in Pregnancy were high (87%) but poor for the Drug Exposure Register (33%).
Conclusions Management of HIV and pregnancy in the North Thames units showed a large amount of consistency with regard to testing policies and management. However, there were a few units that did not offer therapy appropriate for advanced disease despite the recommendations of national bodies and a few units still did not recommend HIV testing to all women.     

Lipid lowering effects of statins and fibrates in the management of HIV dyslipidemias associated with antiretroviral therapy in HIV clinical practice

OBJECTIVES: Dyslipidemia associated with antiretroviral therapy is a common clinical problem among HIV-infected patients. Considering that the challenge of adherence to drugs (both antiretroviral and lipid lowering) may be substantial in routine HIV care, our objective was to evaluate the lipid-lowering effects of statins and fibrates in the management of HIV dyslipidemias in clinical practice setting. METHODS: Retrospective review of 103 ethnically diverse dyslipidemic HIV patients on antiretroviral therapy treated with lipid-lowering drugs (using National Cholesterol Education and Prevention II [NCEP II] guidelines) who were followed for a median of 70 weeks. RESULTS: An overall mean reduction of 16% in total cholesterol, 20% non-HDL cholesterol, and 18% in triglycerides was noted. There were no significant changes in HDL levels. On evaluation of the different drug classes, the mean (median) change in total cholesterol, were -9 (-7)% with fibrates, -11 (-14)% with statins and -23 (-22)% for dual therapy with fibrates and statins. The triglycerides decreased by -11 (-40)% in those treated with fibrates; -1 (-21)% in those with statins alone, and -32 (-42)% in those with dual therapy. Overall less than a fifth of patients reached the defined NCEP target goal reduction. On logistic regression analysis, only stopping protease inhibitors/ritonavir was independently associated with significant cholesterol reduction (OR: 10.14; 95% CI: 2.1-48.9; p < 0.005). CONCLUSION: In a primary care setting, the use of statins and/or fibrates may add to the complexity of HIV care, with only modest lipid lowering effects.