Showing papers in "Hiv Medicine in 2018"

Sexualized drug use ('chemsex') and high-risk sexual behaviours in HIV-positive men who have sex with men.

Abstract: Objectives The incidence of sexually transmitted infections (STI s) and HIV infection remains high in gay, bisexual, and other men who have sex with men (MSM ) in the UK , and sexualized drug use (“chemsex”) and injecting drug use (“slamsex”) may play a part in this. We aimed to characterize HIV ‐positive MSM engaging in chemsex/slamsex and to assess the associations with self‐reported STI diagnoses and sexual behaviours. Methods Data from a 2014 survey of people attending HIV clinics in England and Wales were linked to clinical data from national HIV surveillance records and weighted to be nationally representative. Multivariable logistic regression assessed the associations of chemsex and slamsex with self‐reported unprotected anal intercourse (UAI ), serodiscordant UAI (sdUAI ) (i.e. UAI with an HIV ‐negative or unknown HIV status partner), sdUAI with a detectable viral load (>50 HIV ‐1 RNA copies/mL ), hepatitis C, and bacterial STI s. Results In the previous year, 29.5% of 392 sexually active participants engaged in chemsex, and 10.1% in slamsex. Chemsex was significantly associated with increased odds of UAI [adjusted odds ratio (AOR ) 5.73; P < 0.001], sdUAI (AOR 2.34; P < 0.05), sdUAI with a detectable viral load (AOR 3.86; P < 0.01), hepatitis C (AOR 6.58; P < 0.01), and bacterial STI diagnosis (AOR 2.65; P < 0.01). Slamsex was associated with increased odds of UAI (AOR 6.11; P < 0.05), hepatitis C (AOR 9.39; P < 0.001), and bacterial STI diagnosis (AOR 6.11; P < 0.001). Conclusions Three in ten sexually active HIV ‐positive MSM engaged in chemsex in the past year, which was positively associated with self‐reported depression/anxiety, smoking, nonsexual drug use, risky sexual behaviours, STI s, and hepatitis C. Chemsex may therefore play a role in the ongoing HIV and STI epidemics in the UK.

Highlights of the 2017 European AIDS Clinical Society (EACS) Guidelines for the treatment of adult HIV-positive persons version 9.0.

Abstract: BACKGROUND The European AIDS Clinical Society (EACS) Guidelines have since 2005 provided multidisciplinary recommendations for the care of HIV-positive persons in geographically diverse areas. GUIDELINE HIGHLIGHTS Major revisions have been made in all sections of the 2017 Guidelines: antiretroviral treatment (ART), comorbidities, coinfections and opportunistic diseases. Newly added are also a summary of the main changes made, and direct video links to the EACS online course on HIV Management. Recommendations on the clinical situations in which tenofovir alafenamide may be considered over tenofovir disoproxil fumarate are provided, and recommendations on which antiretrovirals can be used safely during pregnancy have been revised. Renal and bone toxicity and hepatitis C virus (HCV) treatment have been added as potential reasons for ART switches in fully virologically suppressed individuals, and dolutegravir/rilpivirine has been included as a treatment option. In contrast, dolutegravir monotherapy is not recommended. New recommendations on non-alcoholic fatty liver disease, chronic lung disease, solid organ transplantation, and prescribing in elderly are included, and human papilloma virus (HPV) vaccination recommendations have been expanded. All drug-drug interaction tables have been updated and new tables are included. Treatment options for direct-acting antivirals (DAAs) have been updated and include the latest combinations of sofosbuvir/velpatasvir/voxilaprevir and glecaprevir/pibrentasvir. Recommendations on management of DAA failure and acute HCV infection have been expanded. For treatment of tuberculosis (TB), it is underlined that intermittent treatment is contraindicated, and for resistant TB new data suggest that using a three-drug combination may be as effective as a five-drug regimen, and may reduce treatment duration from 18-24 to 6-10 months. CONCLUSIONS Version 9.0 of the EACS Guidelines provides a holistic approach to HIV care and is translated into the six most commonly spoken languages.

Paediatric European Network for Treatment of AIDS (PENTA) guidelines for treatment of paediatric HIV‐1 infection 2015: optimizing health in preparation for adult life

Abstract: The 2015 Paediatric European Network for Treatment of AIDS (PENTA) guidelines provide practical recommendations on the management of HIV-1 infection in children in Europe and are an update to those published in 2009. Aims of treatment have progressed significantly over the last decade, moving far beyond limitation of short-term morbidity and mortality to optimizing health status for adult life and minimizing the impact of chronic HIV infection on immune system development and health in general. Additionally, there is a greater need for increased awareness and minimization of long-term drug toxicity. The main updates to the previous guidelines include: an increase in the number of indications for antiretroviral therapy (ART) at all ages (higher CD4 thresholds for consideration of ART initiation and additional clinical indications), revised guidance on first- and second-line ART recommendations, including more recently available drug classes, expanded guidance on management of coinfections (including tuberculosis, hepatitis B and hepatitis C) and additional emphasis on the needs of adolescents as they approach transition to adult services. There is a new section on the current ART 'pipeline' of drug development, a comprehensive summary table of currently recommended ART with dosing recommendations. Differences between PENTA and current US and World Health Organization guidelines are highlighted and explained.

Chemsex and new HIV diagnosis in gay, bisexual and other men who have sex with men attending sexual health clinics

Abstract: OBJECTIVES The aim of the study was to analyse associations between chemsex and new HIV and sexually transmitted infection (STI) diagnoses among gay, bisexual and other men who have sex with men (GBMSM) accessing sexual health clinics. METHODS A retrospective case note review was carried out for all GBMSM attending two London sexual health clinics between 1 June 2014 and 31 July 2015. RESULTS Chemsex status was documented for 1734 of 1840 patients. Overall, 27.1% (n = 463) disclosed current recreational drug use, of whom 286 (16.5%) disclosed chemsex participation and 74 of 409 (18.1%) injected drugs. GBMSM who were already HIV positive were more likely to disclose chemsex participation [adjusted odds ratio (AOR) 2.55; 95% confidence interval (CI) 1.89-3.44; P < 0.001]. Those disclosing chemsex participation had higher odds of being newly diagnosed with HIV infection (AOR 5.06; 95% CI 2.56-10.02; P < 0.001), acute bacterial STIs (AOR 3.94; 95% CI 3.00-5.17; P < 0.001), rectal STIs (AOR 4.45; 95% CI 3.37-6.06; P < 0.001) and hepatitis C (AOR 9.16; 95% CI 2.31-36.27; P = 0.002). HIV-negative chemsex participants were also more likely to have accessed post-exposure prophylaxis for HIV in the study period and to report sex with a discordant HIV- or hepatitis C virus-infected partner (P < 0.001). CONCLUSIONS Chemsex disclosure in sexual health settings is associated with higher rates of STI diagnoses, including HIV infection and hepatitis C. GBMSM attending sexual health services should therefore be assessed for chemsex participation and disclosure should prompt health promotion, harm minimization and wellbeing interventions.

Towards elimination of HIV transmission, AIDS and HIV-related deaths in the UK.

Abstract: Objectives Our objective was to present recent trends in the UK HIV epidemic (2007-2016) and the public health response. Methods HIV diagnoses and clinical markers were extracted from the HIV and AIDS Reporting System; HIV testing data in sexual health services (SHS) were taken from GUMCAD STI Surveillance System. HIV data were modelled to estimate the incidence in men who have sex with men (MSM) and post-migration HIV acquisition in heterosexuals. Office for National Statistics (ONS) data enabled mortality rates to be calculated. Results New HIV diagnoses have declined in heterosexuals as a result of decreasing numbers of migrants from high HIV prevalence countries entering the UK. Among MSM, the number of HIV diagnoses fell from 3570 in 2015 to 2810 in 2016 (and from 1554 to 1096 in London). Preceding the decline in HIV diagnoses, modelled estimates indicate that transmission began to fall in 2012, from 2800 [credible interval (CrI) 2300-3200] to 1700 (CrI 900-2700) in 2016. The crude mortality rate among people promptly diagnosed with HIV infection was comparable to that in the general population (1.22 vs. 1.39 per 1000 aged 15-59 years, respectively). The number of MSM tested for HIV at SHS increased annually; 28% of MSM who were tested in 2016 had been tested in the preceding year. In 2016, 76% of people started antiretroviral therapy within 90 days of diagnosis (33% in 2007). Conclusions The dual successes of the HIV transmission decline in MSM and reduced mortality are attributable to frequent HIV testing and prompt treatment (combination prevention). Progress towards the elimination of HIV transmission, AIDS and HIV-related deaths could be achieved if combination prevention, including pre-exposure prophylaxis, is replicated for all populations.

The world-wide incidence of Kaposi's sarcoma in the HIV/AIDS era

Abstract: OBJECTIVES Kaposi's sarcoma (KS) is a multicentric angioproliferative cancer of endothelial origin typically occurring in the context of immunosuppression or immunodeficiency. Consequently, KS is one of the most common cancers in HIV-infected individuals and frequently occurs among transplant recipients. Nevertheless, its incidence in different populations is not well understood. METHODS We searched online databases for publications on KS incidence. A random-effect meta-analysis was performed to combine the KS incidences and incidence rate ratios (IRRs) for associated risk factors. RESULTS Seventy-six eligible studies representing 71 time periods were included. For HIV-infected people, the overall KS incidence was 481.54 per 100 000 person-years with a 95% confidential interval (CI) of 342.36-677.32 per 100 000 person-years. HIV-infected men who have sex with men (MSM) had the highest incidence of KS (1397.11 per 100 000 person-years; 95% CI 870.55-2242.18 per 100 000 person-years). The incidence of KS was significantly lower in female than in male individuals (IRR 3.09; 95% CI 1.70-5.62). People receiving highly active antiretroviral therapy (HAART) had a lower incidence compared with people who had never received HAART (IRR 6.57; 95% CI 1.91-24.69). The incidence of KS was 68.59 (95% CI 31.39-149.86) per 100 000 person-years in transplant recipients, 52.94 (95% CI 39.90-70.20) per 100 000 person-years in children with HIV infection, and 1.53 (95% CI 0.33-7.08) per 100 000 person-years in the general population. CONCLUSIONS Globally, a relatively high incidence of KS was found among HIV-seropositive people and, in particular, in HIV-infected MSM. The introduction of HAART has largely prevented the development of KS, but it has not entirely removed the challenge of KS. In Africa, in particular, KS imposes a very heavy disease burden, which can mainly be attributed to the high prevalence of KS-associated herpesvirus and poor access to HAART.

Predictors of CD4 cell recovery following initiation of antiretroviral therapy among HIV-1 positive patients with well-estimated dates of seroconversion

Abstract: OBJECTIVES: To investigate factors that predict speed of recovery and long-term CD4 cell count in HIV-1 seroconverters initiating combination antiretroviral therapy (cART), and to quantify the influence of very early treatment initiation. We make use of all pre-treatment CD4 counts, because analyses using only a single observation at initiation may be subject to biases. METHODS: We used data from the CASCADE (Concerted Action on SeroConversion to AIDS and Death in Europe) multinational cohort collaboration of HIV-1 seroconverters. We analysed pre- and post-treatment data of patients with seroconversion dates estimated January 2003-March 2014 (n = 7600 for primary analysis) using a statistical model in which the characteristics of recovery in CD4 counts are determined by multiple predictive factors. Secondary analyses were performed incorporating uncertainty in the exact timing of seroconversion to allow more precise estimation of the benefit of very early treatment initiation. RESULTS: 'True' CD4 count at cART initiation was the strongest predictor of CD4 count beyond 3 years on cART. Allowing for lack of complete certainty in the date of seroconversion, CD4 recovery was more rapid for patients in whom treatment was initiated within 4 months. For a given CD4 count, higher viral load (VL) at initiation was strongly associated with higher post-treatment CD4 recovery. For other patient and drug characteristics, associations with recovery were statistically significant but small in magnitude. CONCLUSIONS: CD4 count at cART initiation is the most important factor in predicting post-treatment recovery, but VL provides substantial additional information. If cART is initiated in the first 4 months following seroconversion, recovery of CD4 counts appears to be more rapid.

Switching to coformulated rilpivirine (RPV), emtricitabine (FTC) and tenofovir alafenamide from either RPV, FTC and tenofovir disoproxil fumarate (TDF) or efavirenz, FTC and TDF: 96‐week results from two randomized clinical trials

Abstract: OBJECTIVES The single-tablet regimen rilpivirine, emtricitabine and tenofovir alafenamide (RPV/FTC/TAF) for treatment of HIV-1-infected adults was approved based on bioequivalence. We assessed the clinical efficacy, safety and tolerability of switching to RPV/FTC/TAF from either RPV/FTC/tenofovir disoproxil fumarate (TDF) or efavirenz (EFV)/FTC/TDF. METHODS We conducted two distinct randomized, double-blind, active-controlled, noninferiority trials in participants taking RPV/FTC/TDF (Study 1216) and EFV/FTC/TDF (Study 1160). Each study randomized virologically suppressed (HIV-1 RNA < 50 copies/mL) adults (1:1) to switch to RPV/FTC/TAF or continue their current regimen for 96 weeks. We evaluated efficacy as the proportion with HIV-1 RNA < 50 copies/mL using the Food and Drug Administration snapshot algorithm and prespecified bone and renal endpoints at week 96. RESULTS We randomized and treated 630 participants in Study 1216 (RPV/FTC/TAF, n = 316; RPV/FTC/TDF, n = 314) and 875 in Study 1160 (RPV/FTC/TAF, n = 438; EFV/FTC/TDF, n = 437). In both studies, the efficacy of switching to RPV/FTC/TAF was noninferior to that of continuing baseline therapy at week 96, with respective percentages of patients with HIV RNA < 50 copies/mL being 89.2% versus 88.5% in Study 1216 [difference 0.7%; 95% confidence interval (CI) -4.3 to +5.8%] and 85.2% versus 85.1% in Study 1160 (difference 0%; 95% CI -4.8 to +4.8%). No participant on RPV/FTC/TAF developed treatment-emergent resistance versus two on EFV/FTC/TDF and one on RPV/FTC/TDF. Compared with continuing baseline therapy, significant improvements in bone mineral density and renal tubular markers were observed in the RPV/FTC/TAF groups (P < 0.001). CONCLUSIONS Switching to RPV/FTC/TAF from RPV/FTC/TDF or EFV/FTC/TDF was safe and effective and improved bone mineral density and renal biomarkers up to 96 weeks with no cases of treatment-emergent resistance.

Rates of sustained virological response 12 weeks after the scheduled end of direct-acting antiviral (DAA)-based hepatitis C virus (HCV) therapy from the National German HCV registry: does HIV coinfection impair the response to DAA combination therapy?

Abstract: OBJECTIVES The European Association for the Study of the Liver (EASL) treatment recommendations for hepatitis C no longer discriminate between HIV/hepatitis C virus (HCV)-coinfected and HCV-monoinfected patients. However, recent data from Spain are questioning these recommendations on the basis of the findings of higher relapse rates and lower cure rates in HIV/HCV-infected subjects. The aim of our study was to compare HCV cure rates in monoinfected and coinfected patients from Germany. METHODS Data acquired from the Deutsches Hepatitis C-Registry were analysed. A total of 5657 HCV-monoinfected subjects and 488 HIV/HCV-coinfected patients were included in the study. Rates of sustained virological response 12 weeks after the scheduled end of therapy (SVR12) were collected in both subgroups and in cirrhotic and noncirrhotic patients. RESULTS HIV/HCV-coinfected patients were more frequently male (84.6% vs. 56.4%, respectively; P 350 cells/μL in 63.1% of HIV-positive subjects and 88.7% were on antiretroviral therapy. SVR12 rates were 90.3% (5111 of 5657) in our HCV-monoinfected cohort and 91.2% (445 of 488) in our coinfected patients. Liver cirrhosis was confirmed in 1667 of 5657 (29.5%) monoinfected patients and 84 of 488 (17.2%; P < 0.001) coinfected patients. SVR12 rates did not differ between HCV-monoinfected and HIV/HCV-coinfected patients with liver cirrhosis (87.8% vs. 89.3%, respectively; P = 0.864). A treatment duration of 8 weeks did not reduce the percentage of patients with SVR12 in either subgroup (93.7% in both groups). CONCLUSIONS We found high SVR12 rates in monoinfected as well as coinfected individuals. No differences were detected between the two subgroups regardless of whether there was accompanying liver cirrhosis or a shortened treatment duration.

Efficacy and tolerability of lamivudine plus dolutegravir as a switch strategy in a multicentre cohort of patients with suppressed HIV-1 replication

Abstract: Objectives We evaluated the efficacy and tolerability of lamivudine + dolutegravir in a cohort of HIV-1 infected, treatment-experienced patients with undetectable HIV-RNA. Methods Time to treatment discontinuation (TD) and virological failure (VF) and their predictors were assessed in a multicenter cohort of HIV-1 infected patients, starting lamivudine + dolutegravir after reaching viral suppression. Secondary objective was the evaluation of changes in lipid profile, renal and immunological functions at week 48. Results We enrolled 206 patients (72.8% male, with 51 years median age), who mainly switched their antiretroviral therapy for simplification (32.5%) or drug toxicity (54.5%). The estimated probability of maintaining virological suppression at 48 and 96 weeks was 98.2% and 95.1%, respectively. VF was independently predicted by cumulative time on antiretroviral therapy. The estimated probability of remaining on lamivudine plus dolutegravir was 86.7% and 80.5% at week 48 and 96, respectively. A significant improvement in immunological function (CD4 count and CD4/CD8 ratio) was evidenced at week 48, as well as a decrease in total cholesterol/HDL ratio, triglycerides and estimated glomerular filtration rate. Conclusions Lamivudine plus dolutegravir was effective in maintaining viral suppression in our cohort and led to an improvement in metabolic and immunologic functions.

Nucleoside reverse transcriptase inhibitor-reducing strategies in HIV treatment: assessing the evidence.

Abstract: Antiretroviral (ARV) therapy, comprising a backbone of two nucleos(t)ide reverse transcriptase inhibitors (NRTIs) plus another ARV, is the recognized standard of care (SOC), which has helped extend life expectancy in people living with HIV. In a quest to reduce lifelong drug exposure and minimize or avoid the toxicity of NRTIs, "NRTI-reducing" regimens have been investigated. This descriptive review assessing the results of NRTI-reducing strategies from the largest randomized trials focuses on virological efficacy, resistance, regimen safety (in terms of bone mineral density, renal function, lipids and central nervous system function) and simplicity. The review considers efficacy across various NRTI-sparing strategies, for example an integrase strand transfer inhibitor (INSTI) plus a ritonavir-boosted protease inhibitor (PI/r) or PI/r + lamivudine (3TC), in both naive and switch regimes. Of 10 key studies in treatment-naive adults assessing five NRTI-reducing strategies, only four studies demonstrated noninferiority vs. SOC [GARDEL, NEAT 001, AIDS Clinical Trials Group 5142 and PROGRESS]. In switch settings, 17 studies (10 randomized) were reviewed that used four strategies, including three studies assessing an INSTI plus a nonnucleoside reverse transcriptase inhibitor . Noninferiority of the NRTI-reducing arm was shown in six of 10 studies (ATLAS-M, SALT, DUAL, OLE, LATTE-2 and SWORD). In general, NRTI-reducing therapy did not always result in an improvement in short- or long-term adverse events; however, in many cases, these endpoints were not reported. Some of these studies reported higher virological failure rates with more frequent emergence of resistance mutations. None of these NRTI-reducing strategies has been compared against a single-pill regimen, including those containing tenofovir alafenamide. Only strategies demonstrating noninferior efficacy, a benefit in safety/tolerability, and a favourable cost-efficacy ratio, preferably in a single pill, will eventually match the current SOC of triple ARV therapy.

Association between exposure to antiretroviral drugs and the incidence of hypertension in HIV-positive persons: the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study.

Abstract: Objectives Previous studies have suggested that hypertension in HIV-positive individuals is associated primarily with traditional risk factors such as older age, diabetes and dyslipidaemia. However, controversy remains as to whether exposure to antiretroviral (ARV) drugs poses additional risk, and we investigated this question in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) cohort. Methods The incidence of hypertension [systolic blood pressure (BP) > 140 and/or diastolic BP > 90 mmHg and/or initiation of antihypertensive treatment] was determined overall and in strata defined by demographic, metabolic and HIV-related factors, including cumulative exposure to each individual ARV drug. Predictors of hypertension were identified using uni- and multivariable Poisson regression models. Results Of 33 278 included persons, 7636 (22.9%) developed hypertension over 223 149 person-years (PY) [incidence rate: 3.42 (95% confidence interval (CI) 3.35-3.50) per 100 PY]. In univariable analyses, cumulative exposure to most ARV drugs was associated with an increased risk of hypertension. After adjustment for demographic, metabolic and HIV-related factors, only associations for nevirapine [rate ratio 1.07 (95% CI: 1.04-1.13) per 5 years] and indinavir/ritonavir [rate ratio 1.12 (95% CI: 1.04-1.20) per 5 years] remained statistically significant, although effects were small. The strongest independent predictors of hypertension were male gender, older age, black African ethnicity, diabetes, dyslipidaemia, use of lipid-lowering drugs, high body mass index (BMI), renal impairment and a low CD4 count. Conclusions We did not find evidence for any strong independent association between exposure to any of the individual ARV drugs and the risk of hypertension. Findings provide reassurance that screening policies and preventative measures for hypertension in HIV-positive persons should follow algorithms used for the general population.

HIV incidence is rapidly increasing with age among young men who have sex with men in China: a multicentre cross-sectional survey.

Abstract: OBJECTIVES The HIV epidemic is worsening among men who have sex with men (MSM) in China, especially among those who are younger than 25 years old [younger MSM (YMSM)]. The aim of the study was to compare the prevalences of HIV incidence and recent HIV infection as well as factors associated with recent HIV infection in YMSM and older MSM (OMSM). METHODS A multicentre cross-sectional survey was conducted among 4496 MSM recruited from seven Chinese cities. YMSM were defined as those aged < 25 years. Data on demographics and sexual behaviours were collected using structural questionnaires. Blood samples were tested for recent HIV infection and other sexually transmitted infections. RESULTS Among the participants, 1313 were YMSM and 3183 were OMSM. Compared with OMSM, YMSM had a higher prevalence of recent HIV infection [5.4% (71 of 1313) for YMSM vs. 3.6% (115 of 3175) for OMSM; P = 0.006] and a higher HIV incidence [11.8 per 100 person-years (PY) (95% confidence interval (CI) 9.0-14.5) for YMSM vs. 7.6 per 100 PY (95% CI 6.3-9.0) for OMSM]. The incidence increased with age among YMSM, especially between the ages of 16 and 21 years. In contrast, the incidence declined with age among OMSM. Anal bleeding, recreational drug use, syphilis and herpes simplex virus 2 (HSV-2) infection were independent risk factors for recent HIV infection among YMSM. The prevalence of all these risk factors increased with age between the ages of 16 and 21 years. Anal bleeding (19.8%) and recreational drug use (19.5%) had the highest adjusted population attributable fractions (aPAFs) among YMSM. The highest aPAFs of anal bleeding (27.4%) and syphilis infection (25.5%) were found between the ages of 19 and 21 years. CONCLUSIONS The HIV incidence in Chinese YMSM was significantly higher than that in OMSM. YMSM aged 16-21 years had an extremely high risk of recent HIV infection.

Evolution of transmitted HIV-1 drug resistance and viral subtypes circulation in Italy from 2006 to 2016

Abstract: OBJECTIVES The aim was to evaluate the evolution of transmitted HIV-1 drug resistance (TDR) prevalence in antiretroviral therapy (ART)-naive patients from 2006 to 2016. METHODS HIV-1 sequences were retrieved from the Antiviral Response Cohort Analysis (ARCA) database and TDR was defined as detection of at least one mutation from the World Health Organization (WHO) surveillance list. RESULTS We included protease/reverse transcriptase sequences from 3573 patients; 455 had also integrase sequences. Overall, 68.1% of the patients were Italian, the median CD4 count was 348 cells/μL [interquartile range (IQR) 169-521 cells/μL], and the median viral load was 4.7 log10 HIV-1 RNA copies/mL (IQR 4.1-5.3 log10 copies/mL). TDR was detected in 10.3% of patients: 6% carried mutations to nucleos(t)ide reverse transcriptase inhibitors (NRTIs), 4.4% to nonnucleos(t)ide reverse transcriptase inhibitors (NNRTIs), 2.3% to protease inhibitors (PIs), 0.2% to integrase strand transfer inhibitors (INSTIs) and 2.1% to at least two drug classes. TDR declined from 14.5% in 2006 to 7.3% in 2016 (P = 0.003): TDR to NRTIs from 9.9 to 2.9% (P = 0.003) and TDR to NNRTIs from 5.1 to 3.7% (P = 0.028); PI TDR remained stable. The proportion carrying subtype B virus declined from 76.5 to 50% (P < 0.001). The prevalence of TDR was higher in subtype B vs. non-B (12.6 vs. 4.9%, respectively; P < 0.001) and declined significantly in subtype B (from 17.1 to 8.8%; P = 0.04) but not in non-B subtypes (from 6.1 to 5.8%; P = 0.44). Adjusting for country of origin, predictors of TDR were subtype B [adjusted odds ratio (AOR) for subtype B vs. non-B 2.91; 95% confidence interval (CI) 1.93-4.39; P < 0.001], lower viral load (per log10 higher: AOR 0.86; 95% CI 0.75-0.99; P = 0.03), site in northern Italy (AOR for southern Italy/island vs. northern Italy, 0.61; 95% CI 0.40-0.91; P = 0.01), and earlier calendar year (per 1 year more recent: AOR 0.95; 95% CI 0.91-0.99; P = 0.02). CONCLUSIONS The prevalence of HIV-1 TDR has declined during the last 10 years in Italy.

InterPrEP: internet‐based pre‐exposure prophylaxis with generic tenofovir disoproxil fumarate/emtrictabine in London – analysis of pharmacokinetics, safety and outcomes

Abstract: Objectives The National Health Service in England (NHS England) does not provide pre-exposure prophylaxis (PrEP) against HIV, forcing people to purchase generic versions on the internet. However, there are concerns about the authenticity of medicines purchased online. We established an innovative service offering plasma tenofovir (TFV) and emcitrabine (FTC) therapeutic drug monitoring for people buying generic PrEP online, to ensure that drug concentrations in vivo were consistent with those of propriety brands and previously published data. Methods TFV/FTC concentrations were measured by ultra-performance liquid chromatography ultraviolet detection. Evaluation of renal function and testing for HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV) were also carried out, at baseline and every 3-6 months, with risk reduction advice. Results A total of 293 individuals presented having purchased PrEP on the internet: 85% were white, 84% were taking daily PrEP, and 16% were event-driven. Most were on generic TFV disoproxil fumarate (TDF)/FTC from Cipla Ltd. Median (range) TFV and FTC plasma concentrations were 104 (21-597) ng/mL and 140 (17-1876) ng/mL, respectively. All concentrations were above our established plasma TFV and FTC targets, based on previously published data. Renal function was normal in all evaluable individuals and no new cases of HIV, HBV or HCV infection were seen. Conclusions In a population at high risk of HIV acquisition, who cannot yet access PrEP on the NHS, concentrations of TFV and FTC in generic formulations purchased over the internet were similar to (or slightly higher than) those measured in phase I studies with the original formulation from Gilead (Truvada™), which has demonstrated high levels of protection against HIV infection in previous PrEP clinical trials.

National audit of perinatal HIV infections in the UK, 2006-2013: what lessons can be learnt?

Abstract: Objectives The aim of the study was to investigate circumstances surrounding perinatal transmissions of HIV (PHIVs) in the UK. Methods The National Study of HIV in Pregnancy and Childhood conducts comprehensive surveillance of all pregnancies in women diagnosed with HIV infection and their infants in the UK; reports of all HIV-diagnosed children are also sought, regardless of country of birth. Children with PHIV born in 2006-2013 and reported by 2014 were included in an audit, with additional data collection via telephone interviews with clinicians involved in each case. Contributing factors for each transmission were identified, and cases described according to main likely contributing factor, by maternal diagnosis timing. Results A total of 108 PHIVs were identified. Of the 41 (38%) infants whose mothers were diagnosed before delivery, it is probable that most were infected in utero, around 20% intrapartum and 20% through breastfeeding. Timing of transmission was unknown for most children of undiagnosed mothers. For infants born to diagnosed women, the most common contributing factors for transmission were difficulties with engagement and/or antiretroviral therapy (ART) adherence in pregnancy (14 of 41) and late antenatal booking (nine of 41); for the 67 children with undiagnosed mothers, these were decline of HIV testing (28 of 67) and seroconversion (23 of 67). Adverse social circumstances around the time of pregnancy were reported for 53% of women, including uncertain immigration status, housing problems and intimate partner violence. Eight children died, all born to undiagnosed mothers. Conclusions Priority areas requiring improvement include reducing incident infections, improving ART adherence and facilitating better engagement in care, with attention to addressing the health inequalities and adverse social situations faced by these women.

Monitoring the HIV continuum of care in key populations across Europe and Central Asia

Abstract: OBJECTIVES The aim of the study was to measure and compare national continuum of HIV care estimates in Europe and Central Asia in three key subpopulations: men who have sex with men (MSM), people who inject drugs (PWID) and migrants. METHODS Responses to a 2016 European Centre for Disease Prevention and Control (ECDC) survey of 55 European and Central Asian countries were used to describe continuums of HIV care for the subpopulations. Data were analysed using three frameworks: Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 targets; breakpoint analysis identifying reductions between adjacent continuum stages; quadrant analysis categorizing countries using 90% cut-offs for continuum stages. RESULTS Overall, 29 of 48 countries reported national data for all HIV continuum stages (numbers living with HIV, diagnosed, receiving treatment and virally suppressed). Six countries reported all stages for MSM, seven for PWID and two for migrants. Thirty-one countries did not report data for MSM (34 for PWID and 41 for migrants). In countries that provided key-population data, overall, 63%, 40% and 41% of MSM, PWID and migrants living with HIV were virally suppressed, respectively (compared with 68%, 65% and 68% nationally, for countries reporting key-population data). Variation was observed between countries, with higher outcomes in subpopulations in Western Europe compared with Eastern Europe and Central Asia. CONCLUSIONS Few reporting countries can produce the continuum of HIV care for the three key populations. Where data are available, differences exist in outcomes between the general and key populations. While MSM broadly mirror national outcomes (in the West), PWID and migrants experience poorer treatment and viral suppression. Countries must develop continuum measures for key populations to identify and address inequalities.

Factors associated with deaths from suicide in a French nationwide HIV-infected cohort.

Abstract: OBJECTIVES: People living with HIV (PLHIV) are at a higher risk of dying by suicide than the general population. Epidemiological data regarding determinants of suicide in PLHIV are scarce. The aim of this study was thus to study demographic, socio-economic, psychiatric history and immunovirological characteristics associated with death from suicide in the French multicenter Dat'AIDS cohort, from January 2000 to July 2013. METHODS: This was a nested case-control study. All deceased PLHIV during the study period who died by suicide and whose medical files could be checked were included as cases. Controls were selected using incidence density sampling. For each case, up to four controls were selected among all actively followed PLHIV at the index date (date of death of cases). Controls were matched for time from HIV diagnosis (5-year periods) and clinical centre. RESULTS: Seventy cases and 279 controls were included in the study. By multivariable analysis, the factors significantly associated with death from suicide were: not having children, active or substituted drug consumption, alcohol intake > 20 g/day or history of alcohol abuse, history of depressive disorder and/or of attempted suicide, and psychotropic drug intake. Conversely, age, gender, country of birth, positive HCV serology and HIV-related factors, such as AIDS status, use of combination antiretroviral therapy (cART), nadir and current CD4 counts and HIV viral load, were not significantly associated with the risk of death from suicide. CONCLUSIONS: In the cART era, HIV-related factors are not associated with a higher risk of suicide mortality. Suicide prevention measures should target PLHIV with the psychological morbidities observed in our cohort

The challenge of discriminating between HIV-1, HIV-2 and HIV-1/2 dual infections.

Abstract: OBJECTIVES Discrimination between HIV-1 and HIV-2 is important to ensure appropriate antiretroviral treatment (ART) and epidemiological surveillance. However, serological tests have shown frequent mistyping when applied in the field. We evaluated two confirmatory tests, INNO-LIA HIV I/II Score and ImmunoComb HIV 1/2 BiSpot, for HIV type discriminatory capacity. METHODS Samples from 239 ART-naive HIV-infected patients from the Bissau HIV Cohort in Guinea-Bissau were selected retrospectively based on the initial HIV typing performed in Bissau, ensuring a broad representation of HIV types. INNO-LIA results were interpreted by the newest software algorithm, and three independent observers read the ImmunoComb results. HIV-1/HIV-2 RNA and DNA were measured for confirmation. RESULTS INNO-LIA results showed 123 HIV-1 positive samples, 69 HIV-2 positive and 47 HIV-1/2 dually reactive. There was agreement between INNO-LIA and HIV-1/HIV-2 RNA and DNA detection, although not all HIV-1/2 dually reactive samples could be confirmed by the nucleic acid results. Overall, the observers found that the ImmunoComb results differed from the INNO-LIA results, with agreements of 90.4, 91.2 and 92.5%, respectively, for HIV-1, HIV-2 and HIV-1/2. The combined kappa-score for agreement between the three observers was 0.955 (z-score 35.1; P < 0.01). Of the HIV-2 mono-reactive samples (INNO-LIA), the three observers interpreted 24.6-31.9% as HIV-1/2 dually infected by ImmunoComb. None of these samples had detectable HIV-1 RNA or DNA. CONCLUSIONS There was accordance between INNO-LIA calls and nucleic acid results, whereas ImmunoComb overestimated the number of HIV-1/2 dually infected patients. Confirmatory typing is needed for patients diagnosed with HIV-1/2 dual infection by ImmunoComb.

Screening for human papillomavirus, cervical cytological abnormalities and associated risk factors in HIV-positive and HIV-negative women in Rwanda.

Abstract: Objectives Cervical cancer is the major cause of death from cancer in Africa. We wanted to assess the prevalence of human papillomavirus (HPV) infections and associated risk factors and to determine whether HPV testing could serve as a screening method for squamous intraepithelial lesions (SILs) in Rwanda. We also wanted to obtain a broader understanding of the underlying risk factors for the establishment of HPV infection in Rwanda. Methods A total of 206 HIV-positive women, 172 HIV-negative women and 22 women with unknown HIV status were recruited at the University Teaching Hospitals of Kigali (UTHK) and of Butare (UTHB) in Rwanda. Participants underwent an interview, cervical sampling for a Thinprep Pap test and a screening test analysing 37 HPV strains. Results Only 27% of HIV-positive women and 7% of HIV-negative women had been screened for cervical cancer before. HPV16 and HPV52 were the most common HPV strains. HIV-positive women were more commonly infected with high-risk (HR) HPV and multitype HPV than HIV-negative women. The sensitivity was 78% and the specificity 87% to detect high-grade SIL (HSIL) with HPV screening. Among HIV-negative women, being divorced was positively associated with HR-HPV infection, while hepatitis B, Trichomonas vaginalis infection and HR-HPV infection were factors positively associated with SILs. Ever having had gonorrhoea was positively associated with HR-HPV infection among HIV-positive women. HR-HPV infection and the number of live births were positively associated with SILs. Conclusions The currently used quadrivalent vaccine may be insufficient to give satisfactory HPV coverage in Rwanda. HPV Screening may be effective to identify women at risk of developing cervical cancer, particularly if provided to high-risk patients.

HIV/HCV/HBV testing in the emergency department: a feasibility and seroprevalence study

Abstract: Objectives The aims of this study were to to assess the feasibility of simultaneous testing for the blood-borne viruses (BBV), HIV, hepatitis C (HCV) and hepatitis B (HBV), in the Emergency Department (ED) and ascertain the seroprevalence for these three viruses in this setting. Methods A pilot BBV testing program was undertaken as part of routine clinical care in the ED. All ED attendees aged between 16 and 65 years old who were able to consent were tested over a 55 week period on an opt out basis. Patients with positive test results were linked to clinical services. Interventions aimed at improving testing rates were implemented and evaluated by quality improvement (QI) methodology. Results Of 25,520 age-eligible ED attendees, 6108 (24%) underwent BBV testing; an additional 1160 (4.5%) underwent a standalone HIV test (total of 7268 (28%) individuals).There were 83/7268 (1.1%) non-negative (ie reactive or equivocal) results for HIV and 103/6108 (1.7%) and 32/6108 (0.52%) for anti-HCV IgG and HBsAg, respectively. Of these, 12 (0.17%), 16 (0.26%) and 8 (0.13%) were new reactive tests for HIV, HCV and HBV, respectively, which were able to be confirmed on a second test. Specific QI interventions led to temporary increases in testing rates. Conclusions An opt out BBV testing program in the ED is feasible and effective at finding new cases. However, the testing rate was low at 24%. Although QI interventions led to some improvement in testing rates, further studies are required to identify ways to achieve sustained increases in testing in this setting.

HIV: ageing, cognition and neuroimaging at 4-year follow-up.

Abstract: OBJECTIVES The aim of the study was to investigate the hypothesis of accelerated cognitive ageing in HIV-positive individuals using longitudinal assessment of cognitive performance and quantitative magnetic resonance imaging (MRI). METHODS We assessed a broad cognitive battery and quantitative MRI metrics [voxel-based morphometry (VBM) and diffusion tensor imaging (DTI)] in asymptomatic HIV-positive men who have sex with men (15 aged 20-40 years and 15 aged ≥ 50 years), and HIV-seronegative matched controls (nine aged 20-40 years and 16 aged ≥ 50 years). RESULTS Being HIV positive was associated with greater decreases in executive function and global cognition. Additionally, using DTI, we found that the HIV-positive group had a greater increase in mean diffusivity, but we did not find group differences in volume change using VBM. With respect to the HIV status by age group interaction, this was statistically significant for change in global cognition, with older HIV-positive individuals showing greater global cognitive decline, but there were no significant interaction effects on other measures. Lastly, change in cognitive performance was correlated with change in the DTI measures, and this effect was stronger for the HIV-positive participants. CONCLUSIONS In the present study, we found some evidence for accelerated ageing in HIV-positive individuals, with a statistically significant HIV status by age group interaction in global cognition, although this interaction could not be explained by the imaging findings. Moreover, we also found that change in cognitive performance was correlated with change in the DTI measures, and this effect was stronger for the HIV-positive participants. This will need replication in larger studies using a similarly lengthy follow-up period.

HIV‐infected patients' beliefs about their chronic co‐treatments in comparison with their combined antiretroviral therapy

Abstract: Thanks to the success of combination antiretroviral therapy (cART), HIV-infected patients can have almost a normal life expectancy. This has resulted in an aging HIV-infected population with other chronic comorbidities such as cardiovascular diseases, osteoporosis, and depression. Our hypothesis is that patients' perceptions of and attitudes towards their cART, which is perceived as crucial to their survival, differ from their beliefs about their co-treatments, and this may have an impact on their medication adherence. We used the French version of the Beliefs about Medicine Questionnaire (BMQ-f) to measure the perceptions of patients about their co-treatments and the Beliefs about Medicine Questionnaire for Highly Active Antiretroviral Therapy (BMQ-HAART) to measure their beliefs about their cART in a representative sample (n = 150) of patients enrolled in the Swiss HIV Cohort Study (SHCS) and followed at the Infectious Disease Service at the University Hospital in Lausanne, Switzerland. The survey was administered to all eligible patients by the order of their scheduled appointments at the end of their medical visit. The BMQ comprises two subscores: Specific-Necessity (5 identical items in BMQ-f and BMQ-HAART) and Specific-Concerns (also 5 identical items in BMQ-f and BMQ-HAART). The subscores were standardized by dividing the score scale by the number of questions in the scale, resulting in a range of responses between 1 (low) and 5 (high). Self-reported medication adherence was measured using the SHCS Adherence Questionnaire (SHCS-AQ). Adherence was defined as not missing any dose or missing one dose of the treatment in the past 4 weeks. Sociodemographic variables were retrieved by reviewing the SHCS database. A response rate of 73% (109 of 150) was achieved. A total of 105 patients were included in the analysis: their median age was 56 [interquartile range (IQR) 51, 63] years and 74 were male (70%). Eighty-seven patients (83%) were adherent to cART and 75 (71%) were adherent to their co-treatments (P = 0.0001). The standardized mean responses for the BMQ Specific-Necessity subscores were 4.46 [standard deviation (SD): 0.58] and 2.86 (SD: 1.02) for cART and co-treatments, respectively (P < 0.0001). For Specific-Concerns, the standardized mean responses were 2.9 (SD: 1.02) for cART and 4.09 (SD: 1.02) (P < 0.0001) for co-treatments. cART and co-treatment concerns increased as the number of co-treatments increased (P = 0.03 and P < 0.0001, respectively). Patients had higher Necessity and lower Concerns scores for their cART in comparison with their co-treatments. A higher percentage of patients reported being adherent to cART compared with the co-treatments that they reported they were most likely to miss. Further research using a bigger sample size and more objective measures of adherence is needed to explore the association between adherence and patients' perceptions.

Pre-exposure prophylaxis: awareness, acceptability and risk compensation behaviour among men who have sex with men and the transgender population.

Abstract: Objectives This exploratory study examined the facilitators of and barriers to acceptance of pre-exposure prophylaxis (PrEP) and potential risk compensation behaviour emerging from its use among men who have sex with men (MSM) and transgender individuals (TGs) in India. Methods A questionnaire was administered to 400 individuals registered with a targeted intervention programme. Logistic regression models were used to identify facilitators of and barriers to PrEP acceptance. Results The respondents consisted of 68% MSM and 32% TGs. Risk behaviour categorization identified 40% as low risk, 41% as medium risk and, 19% as high risk for HIV infection. About 93% of the respondents were unaware of PrEP, but once informed about it, 99% were willing to use PrEP. The facilitators of PrEP acceptance were some schooling [odds ratio (OR) 2.16; P = 0.51], being married or in a live-in relationship (OR 2.08; P = 0.46), having a high calculated risk (OR 3.12; P = 0.33), and having a high self-perceived risk (OR 1.8; P = 0.35). Increasing age (OR 2.12; P = 0.04) was a significant barrier. TGs had higher odds of acceptance of PrEP under conditions of additional cost (OR 2.12; P = 0.02) and once-daily pill (OR 2.85; P = 0.04). Individuals identified as low risk for HIV infection showed lower odds of potential risk compensation, defined as more sexual partners (OR 0.8; P = 0.35), unsafe sex with new partners (OR 0.71; P = 0.16), and decreased condom use with regular partners (OR 0.95; P = 0.84), as compared with medium-risk individuals. The associations, although not statistically significant, are nevertheless important for public health action given the limited scientific evidence on PrEP use among MSM and TGs in India. Conclusions With high acceptability and a low likelihood of risk compensation behaviour, PrEP can be considered as an effective prevention strategy for HIV infection among MSM and TGs in India.

Stable HIV-1 reservoirs on dolutegravir maintenance monotherapy: the MONODO study.

Abstract: OBJECTIVES Dolutegravir (DTG) is a highly effective integrase inhibitor with a strong genetic resistance barrier and a potential role in simplified HIV maintenance treatment. We assessed the feasibility of DTG maintenance monotherapy and measured HIV reservoirs on DTG monotherapy. METHODS An interventional, open-label, single-arm study including eight virologically suppressed HIV-1-infected patients switched to DTG 50 mg once daily for 24 weeks was performed. HIV-1 RNA levels in plasma and cerebrospinal and seminal fluids were measured at baseline and week 24, as well as HIV-1 DNA in peripheral cells and DTG concentrations in these compartments. RESULTS HIV-1 RNA remained undetectable in all samples of blood, cerebrospinal fluid and sperm throughout the 24 weeks, except for one cerebrospinal fluid sample with a value of 28 HIV-1 RNA copies/mL at week 24. One patient discontinued the study because of a neurological side effect. There was no change in the mean HIV-1 DNA level between baseline and week 24. Plasma and cerebrospinal fluid DTG concentrations reached therapeutic levels in all patients in these two compartments. CONCLUSIONS In this small sample of carefully selected patients, HIV-1 reservoirs were well controlled on DTG monotherapy over a period of 24 weeks. Viral suppression was also maintained throughout follow-up.

A systematic review of risk of HIV transmission through biting or spitting: implications for policy.

Abstract: OBJECTIVES: The perceived threat of HIV transmission through spitting and biting is evidenced by the increasing use of "spit hoods" by Police Forces in the UK. In addition, a draft parliamentary bill has called for increased penalties for assaults on emergency workers, citing the risk of communicable disease transmission as one justification. We aimed to review literature relating to the risk of HIV transmission through biting or spitting. METHODS: A systematic literature search was conducted using Medline, Embase and Northern Lights databases and conference websites using search terms relating to HIV, AIDS, bite, spit and saliva. Inclusion and exclusion criteria were applied to identified citations. We classified plausibility of HIV transmission as low, medium, high or confirmed based on pre-specified criteria. RESULTS: A total of 742 abstracts were reviewed, yielding 32 articles for full-text review and 13 case reports/series after inclusion and exclusion criteria had been applied. There were no reported cases of HIV transmission related to spitting and nine cases identified following a bite, in which the majority occurred between family (six of nine), in fights involving serious wounds (three of nine), or to untrained first-aiders placing fingers in the mouth of someone having a seizure (two of nine). Only four cases were classified as highly plausible or confirmed transmission. None related to emergency workers and none were in the UK. CONCLUSIONS: There is no risk of transmitting HIV through spitting, and the risk through biting is negligible. Post-exposure prophylaxis is not indicated after a bite in all but exceptional circumstances. Policies to protect emergency workers should be developed with this evidence in mind.

Secular trends in opportunistic infections, cancers and mortality in patients with AIDS during the era of modern combination antiretroviral therapy.

Abstract: OBJECTIVES The aim of the study was to estimate the incidence of, determine risk factors for, and investigate the consequences of opportunistic infections (OIs) and malignancies among patients with the acquired immune deficiency syndrome (AIDS) in the era of modern combination antiretroviral therapy (cART). METHODS Three enrolment periods (1998-2002, 2003-2005 and 2006-2012), corresponding to changes in predominant cART regimens, were compared among 1889 participants enrolled in a prospective cohort study, the Longitudinal Study of Ocular Complications of AIDS (LSOCA). Incidences of AIDS-related OIs and cancers were estimated. Multivariate logistic and Cox regression models were used to determine the effect of demographic and clinical characteristics on OIs and mortality. RESULTS Between participants enrolled in the 1998-2002 and 2006-2012 enrolment periods, the incidence of OIs decreased from 27 per 1000 person-years (PY) to 11 per 1000 PY (P < 0.001), and mortality decreased from 41 per 1000 PY to 18 per 1000 PY (P < 0.0001), corresponding to improvements in cART regimens. CONCLUSIONS Improvements in cART regimens led to a progressive decline in the incidence of OIs and mortality between 1999 and 2013 among patients with AIDS in the era of modern cART.

Liver stiffness reduction and serum fibrosis score improvement in HIV/hepatitis C virus-coinfected patients treated with direct-acting antivirals.

Abstract: OBJECTIVES Only a few studies have addressed liver stiffness dynamics after hepatitis C virus (HCV) treatment in patients with HIV/HCV coinfection. The aim was to evaluate the variation in liver stiffness and in serum liver fibrosis scores in HIV/HCV-coinfected patients before and after treatment with direct-acting antivirals (DAAs). METHODS Liver stiffness measured using transient elastography as well as serum liver fibrosis scores [fibrosis-4 (FIB-4) score and the aspartate aminotransferase to platelet ratio index (APRI)] were evaluated before and at 6-12 months after DAA treatment. Variation in the outcome variables was evaluated using the Wilcoxon nonparametric test. Univariate analysis and multivariate regression models were used. RESULTS A total of 78 HIV/HCV-coinfected subjects were included in the study. Median values of hepatic stiffness significantly decreased after DAA treatment compared with baseline [16.8 (interquartile range (IQR) 10.2-27.0) kPa at baseline vs. 9.4 (IQR 6.7-15.0) kPa after DAA treatment; P < 0.01). Further, a decrease in median FIB-4 score [2.8 (IQR 1.5-4.8) vs. 2.0 (IQR 1.3-3.2), respectively; P < 0.01] and APRI [0.9 (IQR 0.5-2.2) vs. 0.4 (IQR 0.2-0.7), respectively; P < 0.01] was found. In univariate analysis, liver stiffness decrease was associated with increasing age, 'other' HCV genotype (vs. G1), the presence of cirrhosis, higher pre-DAA liver stiffness, sofosbuvir-based regimens and longer DAA treatment (all P < 0.05). Multivariate regression confirmed the significance of the association only with higher baseline liver stiffness (P < 0.01). Greater FIB-4 and APRI reductions were associated with higher respective baseline values, while the presence of hepatic steatosis correlated with lower score reduction after DAA. CONCLUSIONS A reduction in liver stiffness and an improvement in fibrosis scores were observed in HIV/HCV-coinfected patients soon after DAA treatment. The clinical implications of these observations need to be evaluated in larger populations with longer follow-up.

Hospital-based routine HIV testing in high-income countries: a systematic literature review.

Abstract: OBJECTIVES: To produce a summary of the published evidence of the barriers and facilitators for hospital-based routine HIV testing in high-income countries. METHODS: Electronic databases were searched for studies, which described the offer of HIV testing to adults attending emergency departments (EDs) and acute medical units (AMUs) in the UK and US, published between 2006 and 2015. Other high-income countries were not included, as their guidelines do not recommend routine testing for HIV. The main outcomes of interest were HIV testing uptake, HIV testing coverage, factors facilitating HIV screening and barriers to HIV testing. Fourteen studies met the pre-defined inclusion criteria and critically appraised using mixed methods appraisal tool (MMAT). RESULTS: HIV testing coverage ranged from 9.7% to 38.3% and 18.7% to 26% while uptake levels were high (70.1-84% and 53-75.4%) in the UK and US, respectively. Operational barriers such as lack of time, the need for training and concerns about giving results and follow-up of HIV positive results, were reported. Patient-specific factors including female sex, old age and low risk perception correlated with refusal of HIV testing. Factors that facilitated the offer of HIV testing were venous sampling (vs. point-of-care tests), commitment of medical staff to HIV testing policy and support from local HIV specialist providers. CONCLUSIONS: There are several barriers to routine HIV testing in EDs and AMUs. Many of these stem from staff fears about offering HIV testing due to the perceived lack of knowledge about HIV. Our systematic review highlights areas which can be targeted to increase coverage of routine HIV testing.

Severe depression as a neuropsychiatric side effect induced by dolutegravir.

Abstract: With great interest we have read the recent article by Hoffmann et al. [1], in which an almost 6% discontinuation rate for dolutegravir (DGV) because of neuropsychiatric adverse events was described in a large cohort study. To illustrate the importance of these findings, we describe two patients with unexpected DGV-associated severe depression, in conjunction with presenting a concise review of the recent literature on DGV-induced depression. The first patient was a 58-year-old man with an unremarkable medical and psychiatric history and a newly diagnosed HIV infection. He was in good health and did not use comedication. His CD4 T-cell count was 549 cells/lL and his viral load was 165 000 HIV-1 RNA copies/mL. No coinfections were diagnosed. One month after his first visit he was started on abacavir/lamivudine/DGV (Triumeq , Viiv Healthcare, Brentford, UK), which he took before sleeping. One week later he began to feel gloomy, followed shortly by feeling extremely depressed. He developed paranoid ideation and short-tempered behaviour. Laboratory testing was unremarkable. Subsequently, Triumeq was stopped and elvitegravir/cobicistat/emtricitabine/tenofovir was started instead. Within 1 week his symptoms improved. Twenty days after the medication switch, his symptoms had resolved completely. Three months later, he felt emotionally stable without any relapse of his depressive symptoms. The second patient was a 52-year-old man with HIV infection whowas switched to DGV, abacavir and lamivudine (Triumeq ) after complaints of tiredness allegedly caused by efavirenz. He did not have a psychiatric history. His HIV-1 viral load was undetectable, his CD4 T-cell count was 738 cells/lL and serology for hepatitis B and C viruses and syphilis was negative. Twomonths after the switch he began to feel mildly depressed. While remaining uninformed of this, his attending physician continued treatment 4 months after switching cART. His symptoms worsened and he developed distressing suicidal thoughts. Finally, on the verge of committing a serious suicide attempt, he was admitted to the psychiatric unit of our hospital. Laboratory screening did not reveal abnormalities; no other potential causes could be identified. cART was switched the same day to boosted darunavir plus tenofovir and emtricitabine. He was started on benzodiazepines (oxazepam 10 mg three times a day). Five days later he was able to be discharged with a significant reduction of his psychiatric symptoms. Two weeks later, his depressive disorder was almost in remission. Three months later he was active again without any of the psychiatric symptoms that had bothered him before. These cases demonstrate that patients without any preexisting history of psychiatric illness can develop severe depressive symptoms after starting a DGV-containing regimen. In both cases, no other predisposing or precipitating factors were found that could explain the onset of depression. The depressive symptoms improved quickly after the withdrawal of DGV, while at the same time neither patient was treated with antidepressants. This strongly suggests a causal relationship. In addition, Hoffmann et al. [1] reported recurrence of neuropsychiatric symptoms upon re-exposure to DGV after earlier discontinuation in six patients. These observations have been confirmed in a case series and three other cohort studies (Table 1) in which the incidence of depression and other neurocognitive side effects that led to withdrawal of DGV appeared to occur more frequently than reported in the registration studies [1–3]. Data from two of these cohort studies suggest that the threshold for intolerability may be lowered by co-administration of abacavir, but more data are needed to draw stronger conclusions [2]. These relatively high discontinuation rates because of neuropsychiatric symptoms are unexpected and in contrast with the data of preceding clinical trials. A recent meta-analysis of clinical trials reported discontinuing dolutegravir because of adverse events in < 2% of patients [4]. A review of five clinical trials, the Observational Pharmaco-Epidemiology Research & Analysis (OPERA) cohort study and 50 cases spontaneously reported to ViiV Healthcare with suicidality reported discontinuation rates because of psychiatric symptoms in only 0.1 to 0.6% of DGV-treated patients [5]. In these trials, depression occurred within 1 month after starting treatment. It is noteworthy that depressive symptoms Correspondence: Dr Mark G. J. de Boer, Department of Infectious Diseases, Leiden University Medical Center, PO Box 9600, Leiden, The Netherlands. Tel: +31715262613; fax: +3175266758; e-mail: m.g.j.de_boer@lumc.nl