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Objectives: The objective of this study was to describe the real-world use and effectiveness of dolutegravir-based regimens (DBRs) in routine clinical practice in the United Kingdom. Methods: Retrospective analysis was conducted using data from four National Health Service trusts using Climate-HIV, an electronic case record system. Eligible patients were aged ≥18 years with HIV-1 infection who were prescribed a DBR from December 2012 to March 2018. Outcome measurements were accessed at DBR initiation and at weeks 24, 48 and 96 and the last recorded visit up to the extraction date (last measurement). The primary endpoint was the proportion of patients with HIV-1 RNA Results: The study cohort included 934 patients; 337 (36%) were female, 414 (47%) were white and 717 (77%) were treatment experienced (TE). The Kaplan–Meier estimated probability of achieving HIV-1 RNA Conclusions: High levels of virologic suppression and low rates of discontinuation of DBRs were seen in a large, diverse, UK-based population with HIV-1 infection. These findings are broadly consistent with efficacy data from phase III studies.

Objectives People with HIV (PWHIV) are likely to need therapies for comorbidities as they age. We assessed risk of drug–drug interactions (DDIs) in PWHIV. Methods The Climate‐HIV electronic recording system was used to cross‐sectionally analyse records from PWHIV aged ≥ 18 years attending four UK HIV units with a current antiretroviral (ARV) prescription in February 2018. Antiretroviral and non‐ARV medications were categorized by clinical significance of DDIs (University of Liverpool DDI tool). Potential DDIs were predicted using treatment guidelines for commonly recorded comorbidities. Results Among 4630 PWHIV (44% female), 41% were ≥ 50 years old. The average number of non‐ARV comedications increased from < 1 for patients aged ≤ 24 years to > 5 for patients aged ≥ 75 years; 65% were taking one or more non‐ARV comedications. The median (interquartile range) number of non‐ARVs was 1 (0–2) and 2 (1–5) for those aged < 50 and ≥ 50 years, respectively. Common comorbidities/concurrent health conditions occurred more frequently in patients aged ≥ 50 years vs . < 50 (53% vs . 34%). Boosted protease inhibitors were associated with the highest proportion of contraindicated comedications; dolutegravir and raltegravir had the fewest. For non‐ARVs, sildenafil and quetiapine were most likely to result in DDIs. Guideline‐recommended treatments for hepatitis C, hepatitis B, and tuberculosis had the highest proportions of contraindications when combined with ARV regimens, while treatments for hepatitis C, malignancy, and mental health conditions had the highest proportion of combinations potentially causing DDIs requiring dose monitoring or adjustment. Conclusions Non‐ARV use by PWHIV is high and increases with age. Treatment decisions for ageing PWHIV should consider guideline recommendations for comorbidities.

The HIV virus is both neurotropic and immunotropic, causing progressive destruction of both systems. Although their frequency has been markedly reduced in the combination antiretroviral therapy (cART) era, neurological presentations and complications of HIV remain common. Neurological opportunistic infections (OI) and diseases occur in advanced HIV disease and include cryptococcal meningitis, progressive multifocal encephalopathy, primary cerebral lymphoma and cerebral toxoplasmosis. Neurological disease directly associated with HIV may occur at any stage in the progress of HIV disease, from the aseptic meningitis of primary HIV infection to AIDS-associated dementia observed in subjects with profound immune deficiency. In the era of effective antiretroviral therapy, where peripheral HIV viral replication is largely controlled, non-HIV-related neurological disease such as stroke is of increasing importance as the HIV population ages.

Objectives To assess sexual health and behaviour outcomes of young adults with perinatally acquired HIV-1 (PaHIV), and audit sexual health interventions against published standards of care. Methods Retrospective case note audit of 16–25-year-olds with PaHIV attending a dedicated transition clinic from January 2005 to 2011. Results Fifty-two young adults, 31 women, median age 20 years. 41 were sexually active; median age of coitarche 16 years. Median number of lifetime partners was 3.5, and five reported non-consensual sex. All had a sexually transmitted infection (STI) screen; 6 were diagnosed with an STI, genital warts (human papilloma virus) most frequently. The median interval from coitarche to first STI screen was 2 years. The pregnancy incidence was 103 per 1000 person years. 18/25 (72%) sexually active women had a cervical smear, four had colposcopy. All patients had hepatitis B virus (HBV) serology. 47 had not been vaccinated against HBV prior to transition. 23 completed HBV vaccination of which 11 had surface antibody >100 IU/ml at 1 year. Conclusions The majority of our cohort was sexually active while still under the care of paediatric health services. Cervical screening and hepatitis B vaccination rates fell short of audit standards. Vaccination for hepatitis B should be considered prior to transfer of care to adult HIV services.

The behavioural effects of hippocampal lesions have been extensively documented in rats. However, paradigms developed for rats cannot be assumed to transfer straightforwardly to mice; the behaviour of the two species differs in many respects. Mice are currently the species of choice for targeted genetic manipulations. A number of these programs aim to modulate hippocampal function. The present studies were therefore designed to provide a behavioural profile of selective, cytotoxic hippocampal lesions in tasks appropriate for mice. The lesions abolished food hoarding from a source outside the home base, and reduced the tendency to displace food pellets from a tube inside the home cage (burrowing). Lesioned mice showed reductions of directed exploration (rearing and head dipping), but not locomotor activity, in a holeboard and open field, and explored the edges of their home cages less when the lids were removed. Nest construction was also impaired. These effects were not due to gross motor impairments, as formal tests revealed no deficiencies in co-ordination or strength. There were suggestions of changes in emotionality, although a more consistent finding was that lesioned mice were often slower to initiate behaviour in novel surroundings, which may be congruent with the other deficits we observed. These results may aid interpretation of the many genetic manipulations that target the hippocampus, and of neurodegenerative conditions that induce hippocampal pathology.

We report an unusual case of extragenital infection with Trichomonas vaginalis of the conjunctiva of a 32-year-old man. Only one other similar case has been reported in the English language literature. The present report reinforces the widening pathologic spectrum of trichomonads in humans, especially in the context of emerging extragenital infections.

BACKGROUND Once-daily nucleoside-sparing combination antiretroviral therapy regimens are attractive options for the treatment of HIV infection. However, the pharmacokinetic profiles of such regimens are often not established. METHODS HIV-infected subjects receiving 245/200 mg of tenofovir/emtricitabine plus 800/100 mg of darunavir/ritonavir once daily with plasma HIV RNA

Background/introduction HIV positive patients with Hepatitis C (HCV) progress to cirrhosis faster than patients without HIV. BHIVA guidelines 2013 recommend surveillance for cirrhosis and hepatocellular carcinoma. Aim(s)/objectives To evaluate the management of patients with HCV and HIV co-infection against current guidelines for surveillance for liver disease, including with Liver Transient Elastography (TE). Methods The clinical records of all patients with HIV and HCV co-infection in the last 10 years were reviewed. Results 41 patients had co-infection; 6 patients spontaneously cleared HCV. 100% (41/41) of all new diagnoses of HCV received HCV RNA measurement. Genotyping carried out in 86% (30/35) of patients and not possible in 6 cases. Annual HCV RNA was carried out in 76% (29/38). Only 8% (3/36) cases had initial TE result. In 17/36 the result was not recorded, and there was no evidence that the TE had been carried out. In 14/36 the patient did not attend the tertiary centre. Two of the initial TEs were reported as normal (less than 7 kPa). For annual TE assessments, 5/36 were reported. Discussion/conclusion Most patients reviewed did not have assessment for liver disease per national guidelines. Our monitoring of patients with HCV and HIV co-infection particularly with liver TE is poor. The main barrier to co-infected patients receiving care is non-attendance at the tertiary centre. The Trust is now a “spoke” in a hepatitis C network and has local TE, which may improve monitoring of co-infected patients. We will re-audit after this programme has been running for one year.

Self-taken samples for sexually transmitted infections (STIs) are being offered to asymptomatic patients attending routine HIV appointments to increase STI testing. Women give a self-taken vaginal sample; heterosexual men give a first-pass urine sample, and men who have sex with men (MSM) additional self-taken rectal and throat samples. While there is evidence that self-taken samples are as accurate as clinician-taken samples, and are well-tolerated, the acceptability of self-taken samples in this setting is unclear.1 ,2 An anonymous survey was offered to all 692 patients attending our outpatient HIV clinic between June and July 2014, of which 121(17.5%) responded. The following data were collected: age; gender; ethnicity; sexual orientation, …

During meiosis DNA double-strand breaks (DSBs) are induced and repaired by homologous recombination to create gene conversion and crossover products. Mostly these DSBs are made by Spo11, which covalently binds to the DSB ends. More rarely in Saccharomyces cerevisiae, other meiotic DSBs are formed by self-homing endonucleases such as VDE, which is site specific and does not covalently bind to the DSB ends. We have used experimentally located VDE-DSB sites to analyse an intermediate step in homologous recombination, resection of the single-strand ending 5′ at the DSB site. Analysis of strains with different mutant alleles of MRE11 (mre11-58S and mre11-H125N) and deleted for EXO1 indicated that these two nucleases make significant contributions to repair of VDE-DSBs. Physical analysis of single-stranded repair intermediates indicates that efficient initiation and processivity of resection at VDE-DSBs require both Mre11 and Exo1, with loss of function for either protein causing severe delay in resection. We propose that these experiments model what happens at Spo11-DSBs after removal of the covalently bound protein, and that Mre11 and Exo1 are the major nucleases involved in creating resection tracts of widely varying lengths typical of meiotic recombination.

Introduction Self-taken samples increase testing for Chlamydia and Gonorrhoea in high-risk asymptomatic populations including HIV-outpatients. Women are offered self-taken vaginal samples; heterosexual men first-pass urine and MSM self-taken rectal and throat samples and first-pass urine. The acceptability of this method of testing is not well understood. Methods An anonymous paper survey was offered to all patients attending outpatient-HIV clinic June–July 2014. Data collected: age, gender, ethnicity, sexual-orientation; perceptions of self-taken samples; whether they tested that day, and why. Results 121 surveys were returned. Median age = 45(20–69)years; 86% male; 68% white British; 73% homosexual. 61/121(50%) rated STI screening as ‘very important’, 48/121(39%) as ‘worthwhile’: 117/121(96%) rated offering self-taken samples in routine HIV clinic as appropriate. 86/121(71%) found the instructions ‘easy’ to follow and 4/121(3%) ‘difficult’. 78/121(64%) said that they thought that self-taken samples are as reliable compared to clinician-taken and 10/121(8%) thought they were more reliable. 60/121(50%) said self-taken samples were as comfortable as clinician-taken; 30/121(25%) said more comfortable. 33/121(27%) responders did self-sampling that day; 78/121(64%) did not. Participants’ reasons for accepting self-taken samples included: ‘It’s easier/quicker than going to a GUM clinic’ (37%); ‘I prefer doing the swabs myself’ (25%). Reasons for not self-sampling included: ‘I haven’t had any sex since my last sexual health screen’ (26%); ‘I was not offered a STI screen today’ (20%); ‘I prefer to go to a GUM clinic’ (16%). Conclusions The self-swab STI screens are acceptable to patients attending HIV outpatients’, and are perceived as being as reliable and as comfortable as clinician-taken samples.

Mice received cytotoxic lesions which selectively removed all of the hippocampus and dentate gyrus except the most ventral portions. They were impaired on both spontaneous and rewarded discrete-trial alternation in T-mazes. Acquisition of reference memory for the location of a hidden platform in the Morris water maze was impaired in lesioned mice. On an elevated Y-maze reference memory task, in which only one arm was rewarded, lesioned mice showed no evidence of learning. In a Lashley III maze task, however, where maze rotation demonstrated that control performance was independent of distal spatial cues, acquisition in the lesioned mice was unimpaired. Control levels of continuous spontaneous alternation in a Y-maze were too low to reveal a hippocampal deficit. A small impairment in acquisition of a multiple-trial passive avoidance task was seen in lesioned mice, despite a small but significant increase in reactivity to the footshock. These results are largely consistent with findings in hippocampal lesioned rats on the same or similar tasks, and reflect a major impairment of spatial cognition, with relative sparing of non-spatial task performance.