St Stephens Center

Handsworth, United Kingdom

St Stephens Center

Handsworth, United Kingdom
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Oroz C.,Chalmers Sexual Health Clinic | Bailey H.,Wrexham Maelor Hospital | Lee J.,Clayton Hospital | Mullan H.,West Hertfordshire Hospitals NHS Trust | Theobald N.,St Stephens Center
International Journal of STD and AIDS | Year: 2012

The prompt and effective treatment of pelvic inflammatory disease (PID) may reduce the risk of complications such as infertility, ectopic pregnancy and pelvic pain.We conducted a national audit to investigate the treatment of women diagnosed with PID and associated rates of partner notification in genitourinary (GU) medicine clinics during 2008 and compared our results with the British Association of Sexual Health and HIV (BASHH) 2005 national guideline. Among a total of 1,105,587 female attendees, national data showed 18,421 cases of PID diagnosed in GU medicine clinics, giving an incidence of 167 cases per 10,000 attendences.We audited a national sample of 1132 PID cases for review. Of those, 504 (44.5%) received a recommended treatment regimen and 447 (39%) of named male contacts were treated. Adherence to recommended treatment and partner notification did not reach national standards.


McCormack S.,University College London | McCormack S.,Chelsea and Westminster Hospital NHS Foundation Trust | Dunn D.T.,University College London | Desai M.,University College London | And 26 more authors.
The Lancet | Year: 2016

Background Randomised placebo-controlled trials have shown that daily oral pre-exposure prophylaxis (PrEP) with tenofovir-emtricitabine reduces the risk of HIV infection. However, this benefit could be counteracted by risk compensation in users of PrEP. We did the PROUD study to assess this effect. Methods PROUD is an open-label randomised trial done at 13 sexual health clinics in England. We enrolled HIV-negative gay and other men who have sex with men who had had anal intercourse without a condom in the previous 90 days. Participants were randomly assigned (1:1) to receive daily combined tenofovir disoproxil fumarate (245 mg) and emtricitabine (200 mg) either immediately or after a deferral period of 1 year. Randomisation was done via web-based access to a central computer-generated list with variable block sizes (stratified by clinical site). Follow-up was quarterly. The primary outcomes for the pilot phase were time to accrue 500 participants and retention; secondary outcomes included incident HIV infection during the deferral period, safety, adherence, and risk compensation. The trial is registered with ISRCTN (number ISRCTN94465371) and ClinicalTrials.gov (NCT02065986). Findings We enrolled 544 participants (275 in the immediate group, 269 in the deferred group) between Nov 29, 2012, and April 30, 2014. Based on early evidence of effectiveness, the trial steering committee recommended on Oct 13, 2014, that all deferred participants be offered PrEP. Follow-up for HIV incidence was complete for 243 (94%) of 259 patient-years in the immediate group versus 222 (90%) of 245 patient-years in the deferred group. Three HIV infections occurred in the immediate group (1·2/100 person-years) versus 20 in the deferred group (9·0/100 person-years) despite 174 prescriptions of post-exposure prophylaxis in the deferred group (relative reduction 86%, 90% CI 64-96, p=0·0001; absolute difference 7·8/100 person-years, 90% CI 4·3-11·3). 13 men (90% CI 9-23) in a similar population would need access to 1 year of PrEP to avert one HIV infection. We recorded no serious adverse drug reactions; 28 adverse events, most commonly nausea, headache, and arthralgia, resulted in interruption of PrEp. We detected no difference in the occurrence of sexually transmitted infections, including rectal gonorrhoea and chlamydia, between groups, despite a suggestion of risk compensation among some PrEP recipients. Interpretation In this high incidence population, daily tenofovir-emtricitabine conferred even higher protection against HIV than in placebo-controlled trials, refuting concerns that effectiveness would be less in a real-world setting. There was no evidence of an increase in other sexually transmitted infections. Our findings strongly support the addition of PrEP to the standard of prevention for men who have sex with men at risk of HIV infection. Funding MRC Clinical Trials Unit at UCL, Public Health England, and Gilead Sciences. © 2016 McCormack et al. Open Access article distributed under the terms of CC BY.


PubMed | Public Health England, University of Liverpool, University of Manchester, Guys and St Thomas NHS Foundation Trust and 12 more.
Type: Journal Article | Journal: Lancet (London, England) | Year: 2016

Randomised placebo-controlled trials have shown that daily oral pre-exposure prophylaxis (PrEP) with tenofovir-emtricitabine reduces the risk of HIV infection. However, this benefit could be counteracted by risk compensation in users of PrEP. We did the PROUD study to assess this effect.PROUD is an open-label randomised trial done at 13 sexual health clinics in England. We enrolled HIV-negative gay and other men who have sex with men who had had anal intercourse without a condom in the previous 90 days. Participants were randomly assigned (1:1) to receive daily combined tenofovir disoproxil fumarate (245 mg) and emtricitabine (200 mg) either immediately or after a deferral period of 1 year. Randomisation was done via web-based access to a central computer-generated list with variable block sizes (stratified by clinical site). Follow-up was quarterly. The primary outcomes for the pilot phase were time to accrue 500 participants and retention; secondary outcomes included incident HIV infection during the deferral period, safety, adherence, and risk compensation. The trial is registered with ISRCTN (number ISRCTN94465371) and ClinicalTrials.gov (NCT02065986).We enrolled 544 participants (275 in the immediate group, 269 in the deferred group) between Nov 29, 2012, and April 30, 2014. Based on early evidence of effectiveness, the trial steering committee recommended on Oct 13, 2014, that all deferred participants be offered PrEP. Follow-up for HIV incidence was complete for 243 (94%) of 259 patient-years in the immediate group versus 222 (90%) of 245 patient-years in the deferred group. Three HIV infections occurred in the immediate group (12/100 person-years) versus 20 in the deferred group (90/100 person-years) despite 174 prescriptions of post-exposure prophylaxis in the deferred group (relative reduction 86%, 90% CI 64-96, p=00001; absolute difference 78/100 person-years, 90% CI 43-113). 13 men (90% CI 9-23) in a similar population would need access to 1 year of PrEP to avert one HIV infection. We recorded no serious adverse drug reactions; 28 adverse events, most commonly nausea, headache, and arthralgia, resulted in interruption of PrEp. We detected no difference in the occurrence of sexually transmitted infections, including rectal gonorrhoea and chlamydia, between groups, despite a suggestion of risk compensation among some PrEP recipients.In this high incidence population, daily tenofovir-emtricitabine conferred even higher protection against HIV than in placebo-controlled trials, refuting concerns that effectiveness would be less in a real-world setting. There was no evidence of an increase in other sexually transmitted infections. Our findings strongly support the addition of PrEP to the standard of prevention for men who have sex with men at risk of HIV infection.MRC Clinical Trials Unit at UCL, Public Health England, and Gilead Sciences.


PubMed | Red Cross, Desmond Tutu HIV Foundation, University of Liverpool, University of New South Wales and 2 more.
Type: Journal Article | Journal: Clinical pharmacokinetics | Year: 2016

ENCORE1 demonstrated non-inferiority of daily efavirenz 400mg (EFV400) versus 600mg (EFV600) to 96weeks in treatment-nave, HIV-infected adults but concerns regarding lower EFV400 concentrations remained. Therefore, relationships between EFV pharmacokinetics (PK) and key genetic polymorphisms with 96-week efficacy and safety were investigated.Relationships between EFV PK parameters and single nucleotide polymorphisms (SNP; CYP2B6, CYP2A6, CYP3A4, NR1I3, NR1I2, ABCB1) with plasma HIV-RNA (pVL) <200 copies/mL and EFV discontinuation and adverse events at 96weeks were explored. Receiver operating characteristic curve analysis evaluated the predictability of mid-dose interval (C12) cutoffs and 96-week pVL.A total of 606 patients (32% female; 37% African, 33% Asian; n=311 EFV400, n=295 EFV600) were included. EFV PK parameters, including C12, were not associated with pVL <200 copies/mL at 96weeks (odds ratio [OR] 5.25, 95% confidence interval [CI] 0.41-67.90, p=0.204). Lower risk of CNS-related adverse events was associated with CYP2B6 983TC/CC (OR 0.35, 95% CI 0.15-0.81, p=0.015) and higher risk was associated with CYP2B6 15582CT/TT and ABCB1 3435TT (OR 1.46, 95% CI 1.02-2.09, p=0.040; OR 2.31, 95% CI 1.33-4.02, p=0.003, respectively). Discontinuation due to adverse events (clinician decision) was independently associated with dose (OR 2.54, 95% CI 1.19-5.43, p=0.016). C12 between 0.47 and 0.76mg/L provided sensitivity/specificity >90% (100%/92.3 to 98.9%/92.3%) for achieving pVL <200 copies/mL at 96weeks.A higher rate of EFV-related adverse events and discontinuations due to these events for EFV600 were not driven by polymorphisms assessed. Although a single threshold concentration associated with HIV suppression may be clinically useful, it was not viable for ENCORE1. Implementation of EFV400 would improve toxicity management whilst still maintaining good efficacy.


Dickinson L.,University of Liverpool | Boffito M.,St Stephens Center | Back D.,University of Liverpool | Else L.,University of Liverpool | And 6 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2011

Nonlinear mixed-effects modeling was applied to explore the relationship between lopinavir and ritonavir concentrations over 72 h following drug cessation and also to assess other lopinavir and ritonavir dosing strategies compared to the standard 400-mg-100-mg twice-daily dose. Data from 16 healthy volunteers were included. Possible covariates influencing lopinavir and ritonavir pharmacokinetics were also assessed. Data were modeled first separately and then together by using individually predicted ritonavir pharmacokinetic parameters in the final lopinavir model. The model was evaluated by means of a visual predictive check and external validation. A maximum-effect model in which ritonavir inhibited the elimination of lopinavir best described the relationship between ritonavir concentrations and lopinavir clearance (CL/F). A ritonavir concentration of 0.06 mg/liter was associated with a 50% maximum inhibition of the lopinavir CL/F. The population prediction of the lopinavir CL/F in the absence of ritonavir was 21.6 liters/h (relative standard error, 14.0%), and the apparent volume of distribution and absorption rate constant were 55.3 liters (relative standard error, 10.2%) and 0.57 h -1 (relative standard error, 0.39%), respectively. Overall, 92% and 94% of the observed concentrations were encompassed by the 95% prediction intervals for lopinavir and ritonavir, respectively, which is indicative of an adequate model. Predictions of concentrations from an external data set (HIV infected) (n = 12) satisfied predictive performance criteria. Simulated lopinavir exposures at lopinavir-ritonavir doses of 200 mg-150 mg and 200 mg-50 mg twice daily were 38% and 65% lower, respectively, than that of the standard dose. The model allows a better understanding of the interaction between lopinavir and ritonavir and may allow a better prediction of lopinavir concentrations and assessments of different dosing strategies. Copyright © 2011, American Society for Microbiology. All Rights Reserved.


Margolis D.A.,Moore Research | Boffito M.,St Stephens Center | Boffito M.,Imperial College London
Current Opinion in HIV and AIDS | Year: 2015

Purpose of review Long-acting antiretroviral (ARV) agents are currently under development for the treatment of chronic HIV infection. This review focuses on data recently produced on injectable ARVs for patients living with HIV/AIDS and on the patients' perspectives on the use of these agents. Recent findings Crystalline nanoparticle formulations of the nonnucleoside reverse transcriptase inhibitor rilpivirine (TMC278) and of the HIV-1 integrase strand transfer inhibitor cabotegravir (GSK1265744) have progressed into phase II clinical trials as injectable maintenance therapy for patients living with HIV/AIDS with an undetectable viral load. Summary Phase II studies evaluating the coadministration of rilpivirine and cabotegravir intramuscularly to HIVinfected individuals with an undetectable viral load are currently underway. Rilpivirine and cabotegravir are characterized by different mechanisms of action against HIV and a favorable drug interaction profile, providing a rationale for coadministration. The high potency and low daily dosing requirements of oral cabotegravir and rilpivirine facilitate long-acting formulation development. Intramuscular dosing is preceded by an oral lead-in phase to assess safety and tolerability in individual participants. In addition to assessing the safety of injectable therapies in ongoing studies, it will be important to evaluate whether differences in drug adherence between injectable and oral therapies lead to different virologic outcomes, including rates of virologic failure and the emergence of resistance. Long-acting formulations may be associated with challenges, such as the management of adverse effects with persistent drug concentrations and the risk of virologic resistance, as drug concentrations decline following discontinuation. © 2015 Wolters Kluwer Health, Inc. All rights reserved.


Roya M.,Jaffray Resource Center | Retzerb A.,National United University | Sikabofori T.,St Stephens Center
Current Opinion in Psychiatry | Year: 2015

Purpose of review: This review examines the factors that shape personality and how they can inform on the behaviour of people with intellectual disability both to help them function at least at their cognitive level and add a developmental dimension to treatment plans.Recent findings: People with intellectual disability experience more failure, rejection and social deprivation leading to personality traits that may impede their ability to learn and predispose them to depression. Brain changes due to genetic conditions may be responsible for the behavioural phenotypes, although the autism phenotype is associated with different causes. Schizophrenia has a strong neurodevelopmental component and it could be on a gradient of decreasing neurodevelopmental impairment between intellectual disability and autism on one hand and bipolar disorder on the other.Summary: Understanding how early-life experience and current-life situations give rise to personality traits and taking a developmental perspective, for example, mental age, could clarify the clinical presentation. Developments in molecular genetics and brain imaging may clarify how brain changes lead to personality features. Finally, it may be time to address whether it is still helpful to have categorical diagnoses when there is increasing evidence from genetic studies supporting a continuum of neurodevelopmental disorders. © Lippincott Williams & Wilkins.


Lewis J.M.,University of Liverpool | Volny-Annec A.,European AIDS Treatment Group | Waittd C.,University of Liverpool | Boffitoe M.,St Stephens Center | Khood S.,University of Liverpool
AIDS | Year: 2016

International tourism continues to increase worldwide, and people living with HIV and their clinicians are increasingly confronted with the problem of how to dose antiretroviral therapy during transmeridian air travel across time zones. No guidance on this topic currently exists. This review is a response to requests from patient groups for clear, practical and evidence-based guidance for travelling on antiretroviral therapy; we present currently available data on the pharmacokinetic forgiveness and toxicity of various antiretroviral regimens, and synthesize this data to provide guidelines on how to safely dose antiretrovirals when travelling across time zones. © 2016 Wolters Kluwer Health, Inc. All rights reserved.


Jones R.,St Stephens Center | Menon-Johansson A.,St Stephens Center | Waters A.M.,St Stephens Center | Sullivan A.K.,St Stephens Center
International Journal of STD and AIDS | Year: 2010

In recent years, the sexual health of the nation has risen in profile. We face increasing demands and targets, in particular the 48-hour waiting time directive, and as a result clinic access has become a priority. eTriage is a novel, secure, web-based service designed specifically to increase access to our clinics. It has proved a popular booking method, providing access to 10% of all appointments across the Directorate within six months of introduction. KC60 analyses revealed that the majority of users (58%) underwent asymptomatic screening with the remainder having some degree of pathology. There was a greater percentage prevalence of human papilloma virus, chlamydia, non-specific urethritis, gonorrhoea, herpes and trichomonas in the eTriage population when compared with the general clinic population. A notes review illustrated a high degree of concordance between data entered on eTriage registration and clinical review (97%). A patient survey revealed high levels of patient satisfaction with the service. As an adjunct to our existing booking services, eTriage has served to increase patient choice and has proved itself to be a safe, efficient and effective means of improving patient access.

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