A national audit of the management of HIV-2 in adults in the UK.

BACKGROUND: HIV-2 is rare in the UK. Many UK centres therefore only treat small numbers of people and there are few clinical trials to guide treatment. The British HIV Association (BHIVA) 2010 guidelines for management of HIV-2 formed the basis for this national audit, which aims to describe current practice and adherence to guidelines. METHODS: All UK centres providing HIV care were contacted via the BHIVA "Members Matters" newsletter, and asked to submit anonymised, retrospective data for individuals living with HIV-2 accessing care at their service. RESULTS: Thirty-five sites responded and data were analysed for 167 individuals. Nearly half of individuals accessed care at one of four large London centres (77/167, 46%).Most people living with HIV-2 have taken antiretroviral therapy (ART) (132/167, 79%). The most common reasons for initiating treatment were clinical disease (34/89, 38%) and pregnancy (11/89, 12%). Most treatment-naïve individuals were initiated on a protease inhibitor based regimen (70/89, 79%). The use of integrase strand transfer inhibitor based regimens has increased over time.A significant minority of patients did not have baseline drug resistance testing performed, despite having a detectable viral load (15/52, 29%). Virological failure occurred in a minority of individuals (21/132, 16%); the most common drug regimen change in this context was the addition of an integrase strand transfer inhibitor (12/26 regimen changes, 46%). CONCLUSIONS: Most individuals living with HIV-2 were managed according to national guidance, with key areas for improvement including the choice of ART, drug resistance testing and the management of virological failure. It is hoped that this national audit, performed in conjunction with the updated 2021 BHIVA guidelines will improve the care of individuals living with HIV-2 in the UK.

Healthcare access for asylum seekers and refugees in England: a mixed methods study exploring service users' and health care professionals' awareness.

BACKGROUND: With the aim of decreasing immigration, the British government extended charging for healthcare in England for certain migrants in 2017. There is concern these policies amplify the barriers to healthcare already faced by asylum seekers and refugees (ASRs). Awareness has been shown to be fundamental to access. This article jointly explores (i) health care professionals' (HCPs) awareness of migrants' eligibility for healthcare, and (ii) ASRs' awareness of health services. METHODS: Mixed methods were used. Quantitative survey data explored HCPs' awareness of migrants' eligibility to healthcare after the extension of charging regulations. Qualitative data from semi-structured interviews with ASRs were analyzed thematically using Saurman's domains of awareness as a framework. RESULTS: In total 514 HCPs responded to the survey. Significant gaps in HCPs' awareness of definitions, entitlements and charging regulations were identified. 80% of HCP respondents were not confident defining the immigration categories upon which eligibility for care rests. Only a small minority (6%) reported both awareness and understanding of the charging regulations. In parallel, the 18 ASRs interviewed had poor awareness of their eligibility for free National Health Service care and suitability for particular services. This was compounded by language difficulties, social isolation, frequent asylum dispersal accommodation moves, and poverty. CONCLUSION: This study identifies significant confusion amongst both HCP and ASR concerning eligibility and healthcare access. The consequent negative impact on health is concerning given the contemporary political climate, where eligibility for healthcare depends on immigration status.

Deaths and parasuicides associated with mefloquine chemoprophylaxis: A systematic review.

BACKGROUND: Mefloquine is recommended in international health guidelines for preventing malaria in travellers. Reports of psychosis and suicide are often alluded to but are not clearly established. METHODS: We carried out a systematic review of the literature to identify and critically appraise any reported death or parasuicide associated with mefloquine prophylaxis. We developed a comprehensive search that included publications up to 11 July 2017. We included case studies but excluded newspaper reports. Two authors independently appraised each death or parasuicide against a standardised causality assessment tool. The protocol was registered on PROSPERO (CRD42016041988). RESULTS: We identified 527 articles that required full-text retrieval; of these 17 were unique publications that reported deaths or parasuicide. Eight unique publications had sufficient detail to be included in causality assessment. We identified 2 deaths with a probable association that appeared to be idiosyncratic drug reactions; we categorised the remaining 8 deaths as "unlikely" to be related to mefloquine, or "unclassifiable". There was one parasuicide with a possible causal association. There were 9 additional publications that searched spontaneous drug reporting databases; none provided sufficient detail to perform a causality assessment. CONCLUSIONS: Overall, the number of deaths that we could reliably attribute to the prophylactic use of mefloquine is very low.

Mefloquine for preventing malaria during travel to endemic areas.

BACKGROUND: Mefloquine is one of four antimalarial agents commonly recommended for preventing malaria in travellers to malaria-endemic areas. Despite its high efficacy, there is controversy about its psychological side effects. OBJECTIVES: To summarize the efficacy and safety of mefloquine used as prophylaxis for malaria in travellers. SEARCH METHODS: We searched the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published on the Cochrane Library; MEDLINE; Embase (OVID); TOXLINE (https://toxnet.nlm.nih.gov/newtoxnet/toxline.htm); and LILACS. We also searched the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP; http://www.who.int/ictrp/en/) and ClinicalTrials.gov (https://clinicaltrials.gov/ct2/home) for trials in progress, using 'mefloquine', 'Lariam', and 'malaria' as search terms. The search date was 22 June 2017. SELECTION CRITERIA: We included randomized controlled trials (for efficacy and safety) and non-randomized cohort studies (for safety). We compared prophylactic mefloquine with placebo, no treatment, or an alternative recommended antimalarial agent. Our study populations included all adults and children, including pregnant women. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the eligibility and risk of bias of trials, extracted and analysed data. We compared dichotomous outcomes using risk ratios (RR) with 95% confidence intervals (CI). Prespecified adverse outcomes are included in 'Summary of findings' tables, with the best available estimate of the absolute frequency of each outcome in short-term international travellers. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included 20 RCTs (11,470 participants); 35 cohort studies (198,493 participants); and four large retrospective analyses of health records (800,652 participants). Nine RCTs explicitly excluded participants with a psychiatric history, and 25 cohort studies stated that the choice of antimalarial agent was based on medical history and personal preference. Most RCTs and cohort studies collected data on self-reported or clinician-assessed symptoms, rather than formal medical diagnoses. Mefloquine efficacyOf 12 trials comparing mefloquine and placebo, none were performed in short-term international travellers, and most populations had a degree of immunity to malaria. The percentage of people developing a malaria episode in the control arm varied from 1% to 82% (median 22%) and 0% to 13% in the mefloquine group (median 1%).In four RCTs that directly compared mefloquine, atovaquone-proguanil and doxycycline in non-immune, short-term international travellers, only one clinical case of malaria occurred (4 trials, 1822 participants). Mefloquine safety versus atovaquone-proguanil Participants receiving mefloquine were more likely to discontinue their medication due to adverse effects than atovaquone-proguanil users (RR 2.86, 95% CI 1.53 to 5.31; 3 RCTs, 1438 participants; high-certainty evidence). There were few serious adverse effects reported with mefloquine (15/2651 travellers) and none with atovaquone-proguanil (940 travellers).One RCT and six cohort studies reported on our prespecified adverse effects. In the RCT with short-term travellers, mefloquine users were more likely to report abnormal dreams (RR 2.04, 95% CI 1.37 to 3.04, moderate-certainty evidence), insomnia (RR 4.42, 95% CI 2.56 to 7.64, moderate-certainty evidence), anxiety (RR 6.12, 95% CI 1.82 to 20.66, moderate-certainty evidence), and depressed mood during travel (RR 5.78, 95% CI 1.71 to 19.61, moderate-certainty evidence). The cohort studies in longer-term travellers were consistent with this finding but most had larger effect sizes. Mefloquine users were also more likely to report nausea (high-certainty evidence) and dizziness (high-certainty evidence).Based on the available evidence, our best estimates of absolute effect sizes for mefloquine versus atovaquone-proguanil are 6% versus 2% for discontinuation of the drug, 13% versus 3% for insomnia, 14% versus 7% for abnormal dreams, 6% versus 1% for anxiety, and 6% versus 1% for depressed mood. Mefloquine safety versus doxycyclineNo difference was found in numbers of serious adverse effects with mefloquine and doxycycline (low-certainty evidence) or numbers of discontinuations due to adverse effects (RR 1.08, 95% CI 0.41 to 2.87; 4 RCTs, 763 participants; low-certainty evidence).Six cohort studies in longer-term occupational travellers reported our prespecified adverse effects; one RCT in military personnel and one cohort study in short-term travellers reported adverse events. Mefloquine users were more likely to report abnormal dreams (RR 10.49, 95% CI 3.79 to 29.10; 4 cohort studies, 2588 participants, very low-certainty evidence), insomnia (RR 4.14, 95% CI 1.19 to 14.44; 4 cohort studies, 3212 participants, very low-certainty evidence), anxiety (RR 18.04, 95% CI 9.32 to 34.93; 3 cohort studies, 2559 participants, very low-certainty evidence), and depressed mood (RR 11.43, 95% CI 5.21 to 25.07; 2 cohort studies, 2445 participants, very low-certainty evidence). The findings of the single cohort study reporting adverse events in short-term international travellers were consistent with this finding but the single RCT in military personnel did not demonstrate a difference between groups in frequencies of abnormal dreams or insomnia.Mefloquine users were less likely to report dyspepsia (RR 0.26, 95% CI 0.09 to 0.74; 5 cohort studies, 5104 participants, low certainty-evidence), photosensitivity (RR 0.08, 95% CI 0.05 to 0.11; 2 cohort studies, 1875 participants, very low-certainty evidence), vomiting (RR 0.18, 95% CI 0.12 to 0.27; 4 cohort studies, 5071 participants, very low-certainty evidence), and vaginal thrush (RR 0.10, 95% CI 0.06 to 0.16; 1 cohort study, 1761 participants, very low-certainty evidence).Based on the available evidence, our best estimates of absolute effect for mefloquine versus doxycyline were: 2% versus 2% for discontinuation, 12% versus 3% for insomnia, 31% versus 3% for abnormal dreams, 18% versus 1% for anxiety, 11% versus 1% for depressed mood, 4% versus 14% for dyspepsia, 2% versus 19% for photosensitivity, 1% versus 5% for vomiting, and 2% versus 16% for vaginal thrush.Additional analyses, including comparisons of mefloquine with chloroquine, added no new information. Subgroup analysis by study design, duration of travel, and military versus non-military participants, provided no conclusive findings. AUTHORS' CONCLUSIONS: The absolute risk of malaria during short-term travel appears low with all three established antimalarial agents (mefloquine, doxycycline, and atovaquone-proguanil).The choice of antimalarial agent depends on how individual travellers assess the importance of specific adverse effects, pill burden, and cost. Some travellers will prefer mefloquine for its once-weekly regimen, but this should be balanced against the increased frequency of abnormal dreams, anxiety, insomnia, and depressed mood.