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Rayment M.,Foundation Medicine | Thornton A.,Public Health England | Mandalia S.,St Stephens AIDS Trust | Elam G.,University College London | And 7 more authors.
PLoS ONE | Year: 2012

Background: UK guidelines recommend routine HIV testing in healthcare settings if the local diagnosed HIV prevalence >2/1000 persons. This prospective study assessed the feasibility and acceptability, to patients and staff, of routinely offering HIV tests in four settings: Emergency Department, Acute Care Unit, Dermatology Outpatients and Primary Care. Modelling suggested the estimated prevalence of undiagnosed HIV infection in attendees would exceed 1/1000 persons. The prevalence identified prospectively was not a primary outcome. Methods: Permanent staff completed questionnaires assessing attitudes towards routine HIV testing in their workplace before testing began. Subsequently, over a three-month period, patients aged 16-65 were offered an HIV test by study staff. Demographics, uptake, results, and departmental activity were collected. Subsets of patients completed questionnaires. Analyses were conducted to identify factors associated with test uptake. Findings: Questionnaires were received from 144 staff. 96% supported the expansion of HIV testing, but only 54% stated that they would feel comfortable delivering testing themselves, with 72% identifying a need for training. Of 6194 patients offered a test, 4105 (66·8%) accepted (61·8-75·4% across sites). Eight individuals were diagnosed with HIV (0-10/1000 across sites) and all transferred to care. Younger people, and males, were more likely to accept an HIV test. No significant associations were found between uptake and ethnicity, or clinical site. Questionnaires were returned from 1003 patients. The offer of an HIV test was acceptable to 92%. Of respondents, individuals who had never tested for HIV before were more likely to accept a test, but no association was found between test uptake and sexual orientation. Conclusions: HIV testing in these settings is acceptable, and operationally feasible. The strategy successfully identified, and transferred to care, HIV-positive individuals. However, if HIV testing is to be included as a routine part of patients' care, additional staff training and infrastructural resources will be required. © 2012 Rayment et al.

Brinson C.,Central Texas Clinical Research | Bogner J.R.,Ludwig Maximilians University of Munich | Nelson M.,St Stephens AIDS Trust | Podzamczer D.,Hospital Universitari Of Bellvitge | And 6 more authors.
Journal of AIDS and Clinical Research | Year: 2013

Background: We report 96- and 144-week follow-up data from VERxVE, demonstrating that nevirapine (NVP) extended release (XR) 400 mg once daily was non-inferior to NVP immediate release (IR) 200 mg twice daily, each administered on a backbone of emtricitabine/tenofovir. Methods: VERxVE was a double-blind, double-dummy, non-inferiority study in adults with screening viral load (VL) >1000 copies/mL and CD4+ cell count <400 cells/mm3 (males) or <250 cells/mm3 (females). Randomisation was stratified by baseline VL (copies/mL) ≤ 100,000 or >100,000. The primary endpoint was confirmed virologic response (<50 copies/mL) at week 48. Cochran's statistic incorporating baseline VL strata tested non-inferiority of XR efficacy versus IR. Secondary endpoints included 144-week sustained virologic response and safety. Results: In all, 1011 patients were randomised and treated with NVP: 736 (XR n=378; IR n= 358) completed 144 weeks. Virologic response was 63.6% for NVP XR and 58.5% for NVP IR (adjusted difference of 4.8% [95% confidence interval -1.1% to 10.8%] favouring NVP XR). No significant differences were seen in changes in CD4+ T-cell counts from baseline, virologic failures or total discontinuation rates between treatment arms, regardless of demographic or baseline characteristics. Conclusions: NVP XR demonstrated non-inferior virologic efficacy to NVP IR in treatment-naïve HIV-infected patients and was well tolerated out to week 144, with a safety profile similar to NVP IR. © 2013 Brinson C, et al.

Vitoria M.,World Health Organization | Hill A.M.,University of Liverpool | Ford N.P.,World Health Organization | Doherty M.,World Health Organization | And 2 more authors.
Journal of the International AIDS Society | Year: 2016

Introduction: There have been several important developments in antiretroviral treatment in the past two years. Randomized clinical trials have been conducted to evaluate a lower dose of efavirenz (400 mg once daily). Integrase inhibitors such as dolutegravir have been approved for first-line treatment. A new formulation of tenofovir (alafenamide) has been developed and has shown equivalent efficacy to tenofovir in randomized trials. Two-drug combination treatments have been evaluated in treatment-naïve and -experienced patients. The novel pharmacokinetic booster cobicistat has been compared to ritonavir in terms of pharmacokinetics, efficacy and safety. The objective of this commentary is to assess recent developments in antiretroviral drug treatment to determine whether new treatments should be included in new international guidelines. Discussion: The use of first-line treatment with tenofovir and efavirenz at the standard 600 mg once-daily dose should remain the first-choice standard of care treatment. Evidence supporting a switch to efavirenz 400 mg once daily or integrase inhibitors is sufficient to consider these drugs as alternative first-line options, but more data are needed on their use in pregnant women and people with TB co-infection. The use of new formulations of tenofovir is currently too preliminary to justify immediate adoption and scale-up across HIV programmes in low- and middle-income countries. The evidence supporting use of two-drug combinations is not considered strong enough to justify changed recommendations from use of standard triple drug combinations. Cobicistat does not offer significant safety advantages over ritonavir as a pharmacokinetic booster. Conclusions: For continued scale-up of antiretroviral treatment in low- and middle-income countries, use of first-line triple combinations including efavirenz 600 mg once daily is supported by the largest evidence base. Additional studies are underway to evaluate new treatments in key populations, and these results may justify changes to these recommendations. © 2016 Vitoria M et al.

Yombi J.C.,Catholic University of Leuven | Pozniak A.,St Stephens AIDS Trust | Boffito M.,St Stephens AIDS Trust | Jones R.,St Stephens AIDS Trust | And 3 more authors.
AIDS | Year: 2014

Assessment of renal function in HIV-positive patients is of increasing importance in the context of ageing and associated comorbidities. Exposure to nephrotoxic medications is widespread, and several commonly used antiretroviral drugs have nephrotoxic potential. Moreover, specific antiretrovirals inhibit renal tubular transporters resulting in the potential for drug-drug interactions as well as increases in serum creatinine concentrations, which affect estimates of glomerular filtration rate in the absence of changes in actual glomerular filtration rate. This review explores the effects of antiretroviral therapy on the kidney and offers an understanding of mechanisms that lead to apparent and real changes in renal function. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Jackson A.,St Stephens AIDS Trust | Kloverpris H.N.,University of Oxford | Kloverpris H.N.,Copenhagen University | Kloverpris H.N.,University of KwaZulu - Natal | And 13 more authors.
PLoS ONE | Year: 2013

Background:Preclinical studies of overlapping 15mer peptides, spanning SIV, SHIV or HIV, pulsed on autologous PBMC ex vivo have demonstrated high level, virus-specific T cell responses and viral suppression in non-human primates (NHP). Opal-HIV-Gag(c) consists of 120 synthetic 15mer peptides spanning Clade C, consensus Gag, manufactured to current good manufacturing practice; having been evaluated in a good laboratory practice toxicology study in Macaca mulatta. We evaluated the safety and preliminary immunogenicity of such peptides administered intravenously after short-duration ex vivo incubation, to HIV-positive adults on suppressive antiretroviral therapy.Methods and Findings:A first-in-human, placebo-controlled, double-blind, dose escalation study was conducted. Twenty-three patients with virus suppressed by antiretroviral therapy were enrolled in four groups 12 mg (n = 6), 24 mg (n = 6), 48 mg (n = 2) or matching placebo (n = 8). Treatment was administered intravenously after bedside enrichment of 120 mL whole blood for white cells using a closed system (Sepax S-100 device), with ex vivo peptide admixture (or diluent alone) and 37°C incubation for one hour prior to reinfusion. Patients received 4 administrations at monthly intervals followed by a 12-week observation post-treatment. Opal-HIV-Gag(c) was reasonably tolerated at doses of 12 and 24 mg. There was an increased incidence of temporally associated pyrexia, chills, and transient/self-limiting lymphopenia in Opal-HIV-Gag(c) recipients compared to placebo. The study was terminated early, after two patients were recruited to the 48 mg cohort; a serious adverse event of hypotension, tachycardia secondary to diarrhoea occurred following a single product administration. An infectious cause for the event could not be identified, leaving the possibility of immunologically mediated product reaction.Conclusions:A serious, potentially life-threatening event of hypotension led to early, precautionary termination of the study. In the absence of a clearly defined mechanism or ability to predict such occurrence, further development of Opal-HIV-Gag(c) will not be undertaken in the current form.Registration:ClinicalTrials.gov NCT01123915; EudraCT: 2008-005142-23. © 2013 Jackson et al.

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