Herbert S.,Mortimer Market Center |
Hewitt K.,Public Health England
Sexually Transmitted Infections | Year: 2014
Notifiable infections can be and often are transmitted sexually and the process of notification often does not work well in the GUM setting. It is the statutory duty of medical practitioners to report notifiable infections, but there are a number of barriers to reporting in sexual health, in particular concerns that notification may breach confidentiality. In this article, we hope to explain the reporting process and aim to highlight why we need to report and what health protection teams do with the information provided. We hope to make the process simple so that GUM clinics can fulfil their public health obligations and enable timely and appropriate public health action to be taken.
Paton N.I.,MRC Clinical Trials Unit |
Goodall R.L.,MRC Clinical Trials Unit |
Dunn D.T.,MRC Clinical Trials Unit |
Franzen S.,Imperial College London |
And 13 more authors.
JAMA - Journal of the American Medical Association | Year: 2012
Context: Therapies to decrease immune activation might be of benefit in slowing HIV disease progression. Objective: To determine whether hydroxychloroquine decreases immune activation and slows CD4 cell decline. Design, Setting, and Patients: Randomized, double-blind, placebo-controlled trial performed at 10 HIV outpatient clinics in the United Kingdom between June 2008 and February 2011. The 83 patients enrolled had asymptomatic HIV infection, were not taking antiretroviral therapy, and had CD4 cell counts greater than 400 cells/μL. Intervention: Hydroxychloroquine, 400 mg, or matching placebo once daily for 48 weeks. Main Outcome Measures: The primary outcome measure was change in the proportion of activated CD8 cells (measured by the expression of CD38 and HLA-DR surface markers), with CD4 cell count and HIV viral load as secondary outcomes. Analysis was by intention to treat using mixed linear models. Results There was no significant difference in CD8 cell activation between the 2 groups (-4.8% and -4.2% in the hydroxychloroquine and placebo groups, respectively, at week 48; difference, -0.6%; 95% CI, -4.8% to 3.6%; P=.80). Decline in CD4 cell count was greater in the hydroxychloroquine than placebo group (-85 cells/μL vs -23 cells/μL at week 48; difference, -62 cells/μL; 95% CI, -115 to -8; P=.03). Viral load increased in the hydroxychloroquine group compared with placebo (0.61 log10 copies/mL vs 0.23 log 10 copies/mL at week 48; difference, 0.38 log 10 copies/mL; 95% CI, 0.13 to 0.63; P=.003). Antiretroviral therapy was started in 9 patients in the hydroxychloroquine group and 1 in the placebo group. Trial medication was well tolerated, but more patients reported influenza-like illness in the hydroxychloroquine group compared with the placebo group (29% vs 10%; P=.03). Conclusion: Among HIV-infected patients not taking antiretroviral therapy, the use of hydroxychloroquine compared with placebo did not reduce CD8 cell activation but did result in a greater decline in CD4 cell count and increased viral replication. Trial Registration; isrctn.org Identifier: ISRCTN30019040. ©2012 American Medical Association. All rights reserved.
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.
Gray E.R.,University College London |
Garson J.A.,University College London |
Breuer J.,University College London |
Edwards S.,Mortimer Market Center |
And 4 more authors.
PLoS ONE | Year: 2011
Background: Several studies have implicated a recently discovered gammaretrovirus, XMRV (Xenotropic murine leukaemia virus-related virus), in chronic fatigue syndrome and prostate cancer, though whether as causative agent or opportunistic infection is unclear. It has also been suggested that the virus can be found circulating amongst the general population. The discovery has been controversial, with conflicting results from attempts to reproduce the original studies. Methodology/Principal Findings: We extracted peripheral blood DNA from a cohort of 540 HIV-1-positive patients (approximately 20% of whom have never been on anti-retroviral treatment) and determined the presence of XMRV and related viruses using TaqMan PCR. While we were able to amplify as few as 5 copies of positive control DNA, we did not find any positive samples in the patient cohort. Conclusions/Significance: In view of these negative findings in this highly susceptible group, we conclude that it is unlikely that XMRV or related viruses are circulating at a significant level, if at all, in HIV-1-positive patients in London or in the general population. © 2011 Gray et al.
Gedela K.,London School of Hygiene and Tropical Medicine |
Edwards S.G.,Mortimer Market Center |
Benn P.,Mortimer Market Center |
Grant A.D.,London School of Hygiene and Tropical Medicine |
Grant A.D.,Mortimer Market Center
International Journal of STD and AIDS | Year: 2014
The objective of this study was to describe the prevalence of vitamin D deficiency among antiretroviral treatment-naïve, HIV-positive individuals. We reviewed records of consecutive antiretroviral treatment-naïve patients, registering for care for the first time at a London clinic from 01 January 2008 to 31 December 2009. During this period, serum 25-hydroxycholecalciferol was measured routinely for all new patients. 25-hydroxycholecalciferol deficiency and severe deficiency were defined as ≤50 and ≤25 nmol/L, respectively. Among 253 patients (82% men, median age 36 years, 64% white ethnicity), 148 (58.5%) were 25-hydroxycholecalciferol-deficient, including 32 (12.6%) who were severely deficient. In all, 73.5% (61/83) patients of non-white ethnicity were 25-hydroxycholecalciferol-deficient compared with 50.7% (76/150) of those reporting white ethnicity (p < 0.001). Seven of eight (87.5%) patients with hypocalcaemia (<2.12 nmol/L) were 25-hydroxycholecalciferol-deficient. The prevalence of 25-hydroxycholecalciferol-deficiency was higher in winter and spring vs. summer and autumn (89/129 [69.0%] vs. 59/124 [47.6%], p < 0.001). Serum 25-hydroxycholecalciferol deficiency was not associated with gender, CD4 count, HIV viral load or clinical stage. Serum 25-hydroxycholecalciferol deficiency was common among antiretroviral treatment-naïve patients, with those of non-white ethnicity at highest risk. CD4 count, HIV viral load and HIV clinical staging do not help to identify those at risk, but low serum calcium should prompt investigation of 25-hydroxycholecalciferol levels. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.
Global trends in antiretroviral resistance in treatment-naïve individuals with HIV after rollout of antiretroviral treatment in resource-limited settings: A global collaborative study and meta-regression analysis
Gupta R.K.,University College London |
Jordan M.R.,Tufts University |
Sultan B.J.,Mortimer Market Center |
Hill A.,University of Liverpool |
And 7 more authors.
The Lancet | Year: 2012
Background The emergence and spread of high levels of HIV-1 drug resistance in resource-limited settings where combination antiretroviral treatment has been scaled up could compromise the eff ectiveness of national HIV treatment programmes. We aimed to estimate changes in the prevalence of HIV-1 drug resistance in treatment-naïve individuals with HIV since initiation of rollout in resource-limited settings. Methods We did a systematic search for studies and conference abstracts published between January, 2001, and July, 2011, and included additional data from the WHO HIV drug resistance surveillance programme. We assessed the prevalence of drug-resistance mutations in untreated individuals with respect to time since rollout in a series of random-eff ects meta-regression models. Findings Study-level data were available for 26 102 patients from sub-Saharan Africa, Asia, and Latin America . We recorded no diff erence between chronic and recent infection on the prevalence of one or more drug-resistance mutations for any region. East Africa had the highest estimated rate of increase at 29% per year (95% CI 15 to 45; p=0·0001) since rollout, with an estimated prevalence of HIV-1 drug resistance at 8 years after rollout of 7·4% (4·3 to 12·7). We recorded an annual increase of 14% (0% to 29%; p=0·054) in southern Africa and a non-signifi cant increase of 3% (-0·9 to 16; p=0·618) in west and central Africa. There was no change in resistance over time in Latin America, and because of much country-level heterogeneity the meta-regression analysis was not appropriate for Asia. With respect to class of antiretroviral, there were substantial increases in resistance to non-nucleoside reverse transcriptase inhibitors (NNRTI) in east Africa (36% per year [21 to 52]; p<0·0001) and southern Africa (23% per year [7 to 42]; p=0·0049). No increase was noted for the other drug classes in any region. Interpretation Our fi ndings suggest a signifi cant increase in prevalence of drug resistance over time since antiretroviral rollout in regions of sub-Saharan Africa; this rise is driven by NNRTI resistance in studies from east and southern Africa. The fi ndings are of concern and draw attention to the need for enhanced surveillance and drug-resistance prevention eff orts by national HIV treatment programmes. Nevertheless, estimated levels, although increasing, are not unexpected in view of the large expansion of antiretroviral treatment coverage seen in low-income and middleincome countries-no changes in antiretroviral treatment guidelines are warranted at the moment.
Hawkes S.,University College London |
Matin N.,International Center for Diarrhoeal Disease Research |
Matin N.,Mortimer Market Center |
Broutet N.,World Health Organization |
Low N.,University of Bern
The Lancet Infectious Diseases | Year: 2011
Background: About 2·1 million pregnant women have active syphilis every year. Without screening and treatment, 69% of these women will have an adverse outcome of pregnancy. The objectives of this study were to review the literature systematically to determine the effectiveness of screening interventions to prevent congenital syphilis and other adverse pregnancy outcomes. Methods: We searched four electronic databases and selected studies to examine evidence for effectiveness of interventions on three outcomes: increased uptake of syphilis testing, increased treatment rates, and reduction in adverse pregnancy outcomes. We used fixed effects meta-analysis to estimate pooled relative risks if no or little evidence of heterogeneity between trials existed. Findings: Ten studies met the inclusion criteria, including two randomised trials. Only two studies aimed to encourage women to seek care earlier in pregnancy. Nine studies included decentralisation of screening and treatment. The effects of the interventions on uptake of testing for antenatal syphilis and receiving at least one dose of penicillin were variable and could not be combined statistically. Study interventions were associated with a reduction in perinatal death (pooled risk ratio [RR] from three studies 0·46, 95% CI 0·26-0·82) and stillbirth (pooled RR from three studies 0·42, 95% CI 0·19-0·93). The incidence of congenital syphilis was reduced in all four studies that measured this outcome with heterogeneous results. Interpretation: Interventions to improve the coverage and effect of screening programmes for antenatal syphilis could reduce the syphilis-attributable incidence of stillbirth and perinatal death by 50%. The resources required to roll out antenatal screening programmes would be a worthwhile investment for reduction of adverse pregnancy outcomes and improvement of neonatal and child survival. Funding: None. © 2011 Elsevier Ltd.
Herbert S.,Mortimer Market Center |
Edwards S.,Mortimer Market Center |
Carrick G.,Mortimer Market Center |
Copas A.,University College London |
And 3 more authors.
Sexually Transmitted Infections | Year: 2012
Objectives: To evaluate the performance and patient acceptability of the PIMA point-of-care (POCT) CD4 test. Methods: Parallel POCT and laboratory CD4 testing were performed in newly diagnosed HIV patients and those with chronic infection attending routine or emergency clinics. Demographics, clinical status and time taken for CD4 results to be available were recorded. Patient acceptability was assessed using a five-point Likert scale. POCT and laboratory results were compared. Results: 283 patients underwent POCT and laboratory CD4 testing. Paired laboratory and POCT results were available in 269 patients. After excluding 15 patients tested during the lead-in period, the test comparison was based on 254 results. Most patients were asymptomatic, male and white British reflecting this patient cohort. 236 patients were chronically infected and 47 were newly diagnosed HIV positive. The POCT result was available within 30 min (86%). The laboratory and POCT results were strongly correlated, r=0.93 (p<0.001), but were generally lower for the POCT (201/ 254 (79%): p<0.001). As a percentage of the laboratory count, the median (95% range) POCT was 87% (57%- 126%). The difference between the POCT and laboratory result was greater for those patients attending the emergency clinic. The sensitivity and specificity of the POCT, to identify patients with laboratory CD4 below 350, were 95% (95% CI 88% to 98%) and 88% (95% CI 82% to 93%), respectively. 235 (83%) patients completed the questionnaire and the POCT was highly acceptable. Conclusions: POCT CD4 was highly correlated with laboratory CD4 testing in this cohort, provided immediate results and was highly acceptable to patients.
Harte D.,Mortimer Market Center |
Mercey D.,University College London |
Jarman J.,Mortimer Market Center |
Benn P.,Mortimer Market Center
Sexually Transmitted Infections | Year: 2011
Objectives: To assess the feasibility and outcomes of recalling men who have sex with men (MSM) diagnosed as having a bacterial sexually transmitted infection (STI) for re-screening. Methods: This evaluation was conducted from December 2008 for a 9-month period. MSM diagnosed as having a bacterial STI in that period were offered recall for re-screening 3 months after their diagnosis. Re-screening rates and infection incidence were calculated. Differences in baseline characteristics by re-screening status and factors predictive of infection at re-screening were assessed using the Mann-Whitney test, χ 2 test and logistic regression. Results: Of the 337 MSM diagnosed as having a bacterial STI, 301 were offered recall. Of these, 206 (68.4%) re-screened after 3 months, 30 (10%) declined and the remainder did not re-attend despite giving verbal consent. Compared with those not re-screening, those re-screening were less likely to be HIV positive (p=0.001), but there was no difference in baseline risk behaviours. There were 15 diagnoses of bacterial STIs at re-screening (29 per 100 person-year follow-up (pyfu); 95% CI 14.3 to 43.7) and five new HIV diagnoses of whom three had a negative test at baseline, one tested negative 6 months earlier and one never tested. Among those testing at both time points, the HIV incidence was 8.3 per 100 pyfu (95% CI 0.0 to 17.7). Conclusions: This evaluation demonstrates a 'recall for re-screening' strategy is feasible in terms of high re-screening rates and incidence of new infections diagnosed. Experimental evidence is needed to assess cost-effectiveness and whether it achieves its aim of reducing transmission of STIs and HIV.
Barber T.J.,Mortimer Market Center |
Benn P.D.,Mortimer Market Center
Current Opinion in HIV and AIDS | Year: 2010
PURPOSE OF REVIEW: Postexposure prophylaxis (PEP) has become an important part of combined approaches to the prevention of onward HIV transmission. As PEP becomes more widely available after sexual as well as occupational exposure, there are ongoing debates about cost-effectiveness and utility. Different regions have adopted different PEP strategies and the availability of new antiretroviral drugs and classes means that options for PEP regimens are increasing. This review is timely and of importance as it summarizes the evidence supporting current PEP usage and discusses potential future strategies for PEP prescribing. RECENT FINDINGS: This review covers the biology and risk of HIV transmission and evidence supporting the use of PEP. It gives a summary of current guidelines including which agents to use, the potential for drug-drug interactions, possible alternative and potential novel PEP regimens, cost-effectiveness and research on effects of PEP on sexual behaviour. SUMMARY: While reinforcing current practice around PEP prescribing, this review discusses possible future developments including the use of new antiretroviral drugs, new classes of antiretroviral drugs or novel strategies for PEP which are likely to be areas of research in the near future. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.