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BACKGROUND Women with HIV face challenges in engaging in HIV care post partum. We aimed to examine changes in engagement in HIV care through clinic attendance before, during, and after pregnancy, compared with matched women with HIV who had never had a recorded pregnancy. METHODS In this cohort study, we describe changes in engagement in HIV care before, during, and after pregnancy among women with HIV from the UK Collaborative HIV Cohort (CHIC) study from 25 HIV clinics in the UK with a livebirth reported to the National Surveillance of HIV in Pregnancy and Childhood between Jan 1, 2000, and Dec 31, 2017. To investigate whether changes were specific to HIV, we compared these changes to those over equivalent periods among non-pregnant women with HIV in the UK CHIC study matched for ethnicity, year of conception, age, CD4 cell count, viral suppression, and antiretroviral therapy use. Analyses were via logistic regression using generalised estimated equations with an interaction between case-control status (pregnant women vs non-pregnant women) and pregnancy or pseudo pregnancy (for non-pregnant women) stage. FINDINGS 1116 matched pairs of pregnant and non-pregnant women were included (median age 34 years [IQR 30-38], 80·1% Black African, 12·5% white). 69 330 person-months of follow-up were recorded, 25 412 in the before stage, 18 897 during, and 25 021 after pregnancy or pseudo pregnancy stages. Among pregnant women, the proportion of time engaged in care increased during pregnancy (8477 [90·5%] of 9371 person-months) and after pregnancy (10 501 [84·6%] of 12 407), compared with before pregnancy (9979 [78·5%] of 12 707). Among non-pregnant women in the control group, engagement in HIV care remained stable across the three equivalent stages (9688 [76·3%] of 12 705 person-months before pseudo pregnancy; 7463 [78·3%] of 9526 during pseudo pregnancy; and 9892 [78·4%] of 12 614 after pseudo pregnancy). The association of engagement in HIV care with pregnancy or pseudo pregnancy stage differed significantly by case-control status (pinteraction

Background: Women ageing with HIV undergo sex-specific changes. There is limited evidence available with regards to how the menopause impacts HIV outcomes. Objective: To investigate whether menopausal age is associated with engagement-in-care (EIC), viral load (VL) suppression and rebound among women living with HIV. Methods: Women were grouped by age (50 years), corresponding to pre-, peri- and post-menopausal stages. EIC, HIV VL suppression (VL < 50 copies/mL) within 12 months of antiretroviral therapy initiation and VL rebound (two consecutive VL > 50 copies/mL) after VL suppression were compared across age groups using logistic/Cox proportional hazards regression. Associations were compared to those seen in heterosexual men. Results: Six thousand four hundred and fifty-five (6455) eligible women (median age 36 [interquartile range: 29–42], 64.4% black African, 19.1% white) contributed 44,226 person-years (PYRS) of follow-up; 29,846, 10,980 and 3,399 PYRS in those aged 50, respectively. Women were engaged-in-care for 79.5% of follow-up time, 3,344 (78.0%) experienced VL suppression and 739 (22.1%) VL rebound. After adjustment, women aged >50 years had lower EIC than those aged

Background In pregnancy, reduction of HIV plasma viral load (pVL) for the prevention of vertical transmission is time-constrained. The study primary objective is to investigate factors associated with faster initial HIV RNA half-life decay when combination antiretroviral treatment (cART) is initiated in pregnancy. Methods This was a multicentre, retrospective, observational study, conducted in south England, United Kingdom, between August 2001 and February 2018. Data were extracted from case notes of eligible women initiating cART during the index pregnancy. Anonymised data were collated and analysed centrally. Regression analyses were conducted to determine factors associated with faster HIV RNA half-life decay in the first 14 days after commencing cART (first-phase), and with achieving an undetectable maternal pVL by 36 weeks’ gestation. We then assessed whether HIV- and obstetric- related parameters differed by antiretroviral third agent class and whether the proportions of women with undetectable pVL at 36 weeks’ gestation and at delivery differed by antiretroviral third agent class. Results Baseline pVL was the only independent factor associated with faster first-phase HIV RNA half-life decay on commencing cART. Lower pVL on day 14 after starting cART was associated with an increased likelihood of achieving an undetectable pVL by 36 weeks’ gestation. Integrase inhibitor-based cART was associated with a faster first-phase HIV RNA half-life decay on commencing cART. Overall, 73% and 85% of women had an undetectable pVL at 36 weeks’ gestation and at delivery respectively, with no significant difference by antiretroviral third agent class. Conclusions Only high baseline pVL independently contributed to a faster rate of first-phase viral half-life decay. pVL at 14 days after initiating cART allows early identification of treatment failure. In the first 14 days after initiating cART in pregnancy, integrase inhibitor-based cART reduced maternal pVL faster than protease inhibitor- and non-nucleoside reverse transcriptase-based cART. While our study findings support INSTI use when initiated in pregnancy especially when initiated at later gestations and in those with higher baseline pVL, other non-INSTI based cART with more data on safety in pregnancy also performed well.

Using data from the PRIME Study, an observational study of the menopause in women living with HIV in England, we explored the association between menopausal symptoms and: (i) antiretroviral therapy (ART) adherence and (ii) HIV clinic attendance. We measured menopausal symptom severity with the Menopause Rating Scale (MRS, score ≥17 indicating severe symptoms), adherence with the CPCRA Antiretroviral Medication Adherence Self-Report Form, and ascertained HIV clinic attendance via self-report. Odds ratios were obtained using logistic regression. Women who reported severe menopausal symptoms had greater odds of suboptimal ART adherence (adjusted odds ratio (AOR) 2.22; 95% CI 1.13, 4.35) and suboptimal clinic attendance (AOR 1.52; 95% CI 1.01, 2.29). When psychological, somatic and urogenital domains of the MRS were analysed individually there was no association between adherence and severe symptoms (all p > 0.1), however there was an association between suboptimal HIV clinic attendance and severe somatic (AOR 1.98; 95% CI 1.24, 3.16) and psychological (AOR 1.76; 95% CI 1.17, 2.65) symptoms. Severe menopausal symptoms were significantly associated with sub-optimal ART adherence and HIV clinic attendance, however we cannot infer causality, highlighting the need for longitudinal data.

We sought to characterize risk factors and patterns of HCV transmission amongst men who have sex with men (MSM). MSM with recently acquired HCV (AHCV) were prospectively recruited ('clinic cohort') between January and September 2017. Clinical data and risk behaviours were identified and blood obtained for HCV whole genome sequencing. Phylogenetic analyses were performed, using sequences from this cohort and two other AHCV cohorts, to identify transmission clusters. Sixteen (40.0%) men in the clinic cohort were HIV-negative MSM. HIV-negative MSM were younger than HIV-positive MSM; most (81.3%) had taken HIV PrEP in the preceding year. Eighteen men (45.0%) reported injection drug use; most (34, 85.0%) reported noninjection drug use in the last year. Most in both groups reported condomless anal sex, fisting and sex in a group environment. Few (7, 17.5%) men thought partners may have had HCV. There were 52 sequences in the HCV genotype 1a phylogeny, 18 from the clinic cohort and 34 from other AHCV cohorts; 47 (90.4%) clustered with ≥1 other sequence. There were 7 clusters of 2-27 sequences; 6 clusters contained HIV-negative and HIV-positive MSM and 1 cluster only HIV-positive MSM. Four of these clusters were part of larger clusters first described in 2007. PrEP-using MSM are at risk of HCV, sharing similar risk factors to HIV-positive MSM. Phylogenetics highlights that PrEP-using and HIV-positive MSM are involved in the same HCV transmission networks. Few men demonstrated HCV awareness and risk reduction strategies should be expanded.

Background Modeling of the London hepatitis C virus (HCV) epidemic in men who have sex with men (MSM) and are living with human immunodeficiency virus (HIV) suggested that early access to direct-acting antiviral (DAA) treatment may reduce incidence. With high rates of linkage to care, microelimination of HCV within MSM living with HIV may be realistic ahead of 2030 World Health Organization targets. We examined trends in HCV incidence in the pre- and post-DAA eras for MSM living with HIV in London and Brighton, United Kingdom. Methods A retrospective cohort study was conducted at 5 HIV clinics in London and Brighton between 2013 and 2018. Each site reported all acute HCV episodes during the study period. Treatment timing data were collected. Incidence rates and reinfection proportion were calculated. Results A total of 378 acute HCV infections were identified, comprising 292 first infections and 86 reinfections. Incidence rates of acute HCV in MSM living with HIV peaked at 14.57/1000 person-years of follow-up (PYFU; 95% confidence interval [CI], 10.95–18.20) in 2015. Rates fell to 4.63/1000 PYFU (95% CI, 2.60 to 6.67) by 2018. Time from diagnosis to starting treatment declined from 29.8 (2013) to 3.7 months (2018). Conclusions We observed a 78% reduction in the incidence of first HCV episode and a 68% reduction in overall HCV incidence since the epidemic peak in 2015, which coincides with wider access to DAAs in England. Further interventions to reduce transmission, including earlier access to treatment and for reinfection, are likely needed for microelimination to be achieved in this population., We examined acute hepatitis C virus (HCV) incidence in men who have sex with men and living with human immunodeficiency virus between 2013 and 2018 in London and Brighton, United Kingdom. Incidence rates peaked in 2015 at 14.57/1000 person-years of follow-up (95% confidence interval, 10.95 to 18.20). Following this there was a 68% reduction in HCV incidence by 2018, coinciding with wider access to direct-acting antivirals.

Objectives We examined follicle-stimulating hormone (FSH) levels in women living with HIV aged > 45 reporting ≥ 12 months' amenorrhoea, and investigated correlation with menopausal symptoms. Methods A cross-sectional substudy of 85 women from the Positive Transitions through the Menopause (PRIME) Study who reported irregular periods at entry into the PRIME Study and ≥ 12 months' amenorrhoea at recruitment into this substudy. Serum FSH was supplemented with clinical data and menopausal symptom assessment. Serum FSH > 30 mIU/mL was defined as consistent with postmenopausal status. Associations between FSH and menopausal symptom severity were assessed using Pearson's correlation and the Kruskal-Wallis test. Results Median age was 53 years [interquartile range (IQR): 51-55]; all were on antiretroviral therapy, three-quarters (n = 65) had a CD4 T-cell count > 500 cells/μL and 91.8% (n = 78) had an HIV viral load (VL) 30 mIU/mL (40.8 vs. 30.5 kg/m2 ). Over a quarter (28.2%) reported severe menopausal symptoms, with no correlation between FSH and severity of menopausal symptoms (p = 0.21), or hot flushes (p = 0.37). Conclusions Four women in this small substudy had low FSH despite being amenorrhoeic; all had BMI ≥ 35 kg/m2 . We found that 95% of women with HIV aged > 45 years reporting ≥ 12 months' amenorrhoea had elevated FSH, suggesting that menopausal status can be ascertained from menstrual history alone in this group.

Background & Aims Shortened duration therapy for acute and recent HCV infection has been shown to be highly effective in several small non-randomised studies with direct-acting antiviral regimens; however, large randomised studies are lacking. Methods REACT was an NIH-funded multicentre international, open-label, randomised, phase IV non-inferiority trial examining the efficacy of short course (6-week) vs. standard course (12-week) therapy with sofosbuvir-velpatasvir for recent HCV infection (estimated duration of infection ≤12 months). Randomisation occurred at week 6. The primary endpoint was sustained virological response 12 weeks after treatment end (SVR12) in the intention-to treat (ITT) population. A total of 250 participants were due to be enrolled, but on advice of the data safety and monitoring board the study was halted early. Results The primary analysis population consisted of 188 randomised participants at termination of study enrolment; short arm (n = 93), standard arm (n = 95). Ninety-seven percent were male and 69% HIV positive. ITT SVR12 was 76/93, 81.7% (95% CI 72.4–89.0) in the short arm and 86/95, 90.5% (95% CI 82.7–95.6) in the standard arm. The difference between the arms was -8.8 (95% CI -18.6 to 1.0). In modified ITT analysis, wherein non-virological reasons for failure were excluded (death, reinfection, loss to follow-up), SVR12 was 76/85, 89.4% (95% CI 80.8–95.0) in the short arm and 86/88, 97.7% in the standard arm (95% CI 92.0–99.7; difference -8.3%, p = 0.025). Conclusions In this randomised study in recent HCV infection, a 6-week course of sofosbuvir-velpatasvir did not meet the criteria for non-inferiority to standard 12-week therapy. Lay summary In this randomised trial, 188 people with recently acquired hepatitis C infection were randomly assigned to treatment using either a short 6-week course (93 people) or standard 12-week course (95 people) of the hepatitis C treatment sofosbuvir/velpatasvir. There were 9 cases of relapse after treatment with the short course and 2 following the standard course. A shortened course of 6-week therapy for hepatitis C infection appeared to be less effective than a standard 12-week course in people with recently acquired hepatitis C infection. ClinicalTrials.gov Identifier NCT02625909 .

The World Health Organisation advice for post-partum women living with HIV (WLHs) in low- and middle-income countries is to breastfeed on suppressive antiretroviral treatment and use infant postnatal prophylaxis. In resource-rich settings, where formula feeding is safe, avoidance of breastfeed is advised. A questionnaire was created to survey attitudes to breastfeeding in WLHs in the United Kingdom. This was offered to all eligible pregnant women in the third trimester or within 3 months post-partum who attended HIV outpatient clinics from 2017 to 2018. Ninety-four women completed the questionnaire, 69% were Black African and 92% had an undetectable HIV viral load. Thirty eight percent stated they would like to breastfeed and 89% said they would breastfeed if they were HIV negative. Sixty two percent had community members question why they did not breastfeed, and 66% felt forced to invent a reason why they were not breastfeeding. Current UK guidelines recommend formula feeding, proposing a harm reduction approach to support women with suppressed HIV who wish to breastfeed. Over a third of respondents said they would like to breastfeed because stigma and secrecy remain an issue for WLHs. This suggests that over time more women may choose this option.

Background Pharmacokinetic and efficacy data on dolutegravir in pregnant women living with human immunodeficiency virus (HIV) are still limited but needed to support its use as one of the preferred antiretroviral agents. Methods Within the multicenter Pharmacokinetics of ANtiretroviral agents in HIV-infected pregNAnt women (PANNA) study, pregnant women living with HIV and using dolutegravir once daily (50 mg, with food) underwent 24-hour pharmacokinetic profiling in their third trimester and postpartum. Dolutegravir exposure in the third trimester was considered adequate if geometric mean unbound, pharmacologically active, minimal plasma concentrations (Cmin, unbound) and ≥90% of individual Cmin, unbound levels were >0.85 µg/L, the proposed 90% inhibitory concentration for unbound dolutegravir. Geometric mean ratios (GMRs) with 90% confidence intervals (CIs) for comparison of total and unbound pharmacokinetic parameters in the third trimester and postpartum were calculated, including the metabolic ratio for dolutegravir-glucuronide. Safety and virological data were collected. Results Seventeen women (76% black) were enrolled (25 evaluable pharmacokinetic profiles; 15 in the third trimester, 10 in postpartum). In the third trimester, geometric mean (coefficient of variation, %) Cmin, unbound was 2.87 (87) µg/L and 93% of individual Cmin, unbound levels were >0.85 µg/L. The GMR (90% CI) in the third trimester vs postpartum was 0.86 (.68–1.10) for area under the curve (AUC0-24h), and for Cmax, 0.93 (.77–1.13). GMR (90% CI) for the trough concentrations was 0.71 (.49–1.02), based on total dolutegravir concentrations. Four serious adverse events were reported, unlikely related to dolutegravir. The HIV polymerase chain reaction test was negative in 14/17 infants (result unknown for 3 infants). Conclusions Pharmacokinetic changes for dolutegravir in late pregnancy are not clinically relevant and support the use of dolutegravir 50 mg once daily with food in pregnancy. Clinical Trials Registration NCT00825929.

Objectives Tenofovir disoproxil fumarate (TDF) is associated with reduced bone mineral density (BMD). We evaluated changes in BMD in women who switched from TDF, emtricitabine and a nonnucleoside reverse transcriptase inhibitor (TDF/FTC/NNRTI) to abacavir, lamivudine and dolutegravir (ABC/3TC/DTG). Methods We conducted a randomized controlled trial in which women aged ≥40 years were randomized 1:2 to continue TDF/FTC/NNRTI or switch to ABC/3TC/DTG. The primary endpoint was change in total hip BMD measured by dual-energy X-ray absorptiometry at week 48. Secondary endpoints were changes in BMD of the lumbar spine and femoral neck and markers of bone turnover and kidney function up to week 48. We conducted exploratory analyses of weight gain, insulin resistance and metabolic syndrome. Primary and secondary endpoints were analysed by linear regression, with multiple imputation for missing time points. Results In all, 91 women [mean age = 50.4 (standard deviation [SD] = 6.6) years, median CD4 cell count = 600 (interquartile range: 479-800) cells/µL] were randomized. Women who switched to ABC/3TC/DTG maintained viral suppression and experienced improvements in total hip BMD (mean adjusted difference = 1%, P = 0.027) and lumbar spine BMD (3%, P = 0.002), with no change in specific markers of bone turnover or renal tubular function. Although participants in the ABC/3TC/DTG arm gained more weight (1.8 kg, P = 0.046), the switch strategy was not associated with reduced insulin sensitivity or new-onset metabolic syndrome. Conclusions Switching from TDF/FTC/NNRTI to ABC/3TC/DTG resulted in improved BMD. Although weight gain was common in women who switched from TDF/FTC/NNRTI to ABC/3TC/DTG, we did not detect adverse effects on glucose homeostasis. Larger studies need to confirm these findings.

In this prospective study conducted from October 2013 to June 2015 in Brighton, England, we examined differences between men and women in new-onset major depressive disorder (MDD) during interferon-alpha-based (IFN-α) therapy for hepatitis C virus (HCV). We included 155 HCV-infected patients (47 women), eligible to receive HCV therapy, including direct-acting antivirals. The Semi-Structured Clinical Interview was used to assess MDD. Severity of depressive symptoms was assessed using the Hamilton Depression Rating Scale. Patients were assessed at baseline, during treatment and 6 months after treatment completion. A significant increase in depressive symptoms was observed in the total sample from baseline to week 4, and a significant decrease was observed from end of treatment (week 24) to the sustained virological response (SVR) end point at 6 months posttreatment. Women were more likely to have a MDD at week 24. In both men and women, neurovegetative and mood-cognitive syndromes increased significantly at the early stage of treatment but remitted by the end of HCV therapy. Proportions with SVR were similar among females and males (91.5 percent vs. 87 percent). Under an inflammatory condition, boosted by interferon-based treatments, these results suggest that female gender is not associated with increased vulnerability for developing depression during IFN-α therapy.

BACKGROUND: We compared the safety and efficacy of three antiretroviral regimens started in pregnancy: dolutegravir (DTG)+emtricitabine (FTC)/tenofovir alafenamide fumarate (TAF); DTG+FTC/tenofovir disoproxil fumarate (TDF); and efavirenz (EFV)/FTC/TDF. METHODS: Women with HIV-1 infection at 22 sites in 9 countries were randomized 1:1:1 at 14–28 weeks’ gestation to start each regimen (open-label). The primary efficacy outcome was virologic non-inferiority at delivery (−10% margin) of the combined DTG groups versus the EFV group, with superiority tested in a pre-planned secondary analysis. Primary safety outcomes, compared pairwise among treatment groups, were occurrence of any adverse pregnancy outcome (preterm delivery, small for gestational age, stillbirth, or spontaneous abortion) and occurrence of maternal and infant adverse events, grade ≥3. Primary analyses were intention-to-treat (ITT). FINDINGS: We enrolled 643 women: 217 DTG+FTC/TAF, 215 DTG+FTC/TDF, 211 EFV/FTC/TDF. Enrollment medians were 22 weeks’ gestation, HIV-1 RNA 903 copies/mL (28%

In 2016, the Prevention Access Campaign, launched the Undetectable=Untransmittable statement.1 U=U is arguably the single most important communication for people living with HIV and is based on a solid foundation of scientific evidence. The zero risk of sexual …

Human immunodeficiency virus (HIV) transmission among women remains an issue in the WHO European Region, with nearly 50,000 women diagnosed in 2018 and over half (54%) diagnosed late. Although new HIV diagnoses declined between 2009 and 2018 in the West of the Region, they increased in the Centre and East. Understanding the characteristics of women diagnosed with HIV can inform gender-sensitive prevention services including pre-exposure prophylaxis and early testing and linkage to care.

Introduction In view of advances in viral hepatitis treatment, future chronic liver disease (CLD) in people living with HIV (PLWH) is likely to be due to non-viral hepatitis aetiologies. Potential contributors include alcohol, metabolic syndrome (MS) or antiretrovirals (ARV). Understanding risk factors and early recognition of CLD is essential to prevent long-term morbidity and mortality. This prospective cohort study investigates the prevalence and predictors of CLD in PLWH with abnormal liver function. Methods Inclusion criteria were PLWH, negative viral hepatitis serology and elevated transaminases over 6 months. Consenting individuals completed an Alcohol Use Disorders Identification Test (AUDIT), underwent MS assessment and transient elastography. Study definitions: significant hepatic steatosis (SHS) - controlled attenuation parameter (CAP) ≥237dB/m; significant hepatic fibrosis (SHF) and cirrhosis - liver stiffness measurement ≥7.1 kPa and ≥11.5 kPa respectively. SHF risk factors consisted of MS, hazardous drinking (AUDIT≥8) and hepatotoxic ARV use. Results Of 429 eligible individuals, 219 have been recruited. Mean age was 52.3±9.8 years, 92.2% were male, 96.3% with undetectable viral load, mean HIV duration of 15.8±7.6 years. Overall prevalence of SHS was 63% (n=137), and SHF was 21% (n=47), of whom 35 (74%) had SHS and 17 (36%) had cirrhosis. On binary logistic regression, HDL and AUDIT score were significantly associated with SHF whereas CD4 baseline, HIV duration, BMI, hypertension, diabetes, and duration on ARV were not. Predictors of SHS included BMI, HDL and AUDIT score. No classical risk factors were identified in 8 (17%) individuals with SHF but they had significantly shorter HIV duration and higher peak ALT compared to those with risk factors for SHF (table 1). Conclusion There is considerable liver disease burden in PLWH with elevated transaminases, with nearly 2/3 having SHS and 1/5 SHF. MS risk factors and alcohol use appear to predict both SHS and SHF. However, one fifth of individuals with SHF have no identifiable risk factors, raising the real possibility of immune dysregulation or direct hepatotoxicity of HIV in this subpopulation. Our data highlights the need to implement screening strategies for CLD in PLWH alone to ensure timely Hepatology input, and the importance of providing appropriate advice regarding alcohol intake and weight loss.

Couples wishing to have biological children when one partner is HIV positive and the other is HIV negative present clinicians with complex clinical, social and ethical considerations. We established two multidisciplinary pre-conception services for HIV-positive individuals and their partners. We report the first UK use of pre-exposure prophylaxis for conception (PrEP-C) as part of an overall risk reduction strategy. Couples were counselled and written informed consent for PrEP-C was obtained. Patient demographics, HIV and medical histories were recorded. Males underwent baseline semen analysis and seminal HIV viral load testing. Females had full fertility screens. Both partners were screened for sexually transmitted infections. All couples used timed ovulatory intercourse (TOI). Tenofovir±emtricitabine was taken by the female at protocol designated times before±after TOI. Thirty-two male positive/female negative couples used the services. Thirteen couples have used PrEP-C (median age of male 41 years (range 32-56), female 31 (28-43); median CD4 533 (236-1194); all male plasma and seminal HIV viral loads were undetectable). Eleven pregnancies in 10 couples have resulted in 7 live births, 1 ongoing pregnancy and 4 miscarriages (5/40, 6/40, 10/40 and 1 twin 17/40) after a median of 2.5 attempts (range 1-5). PrEP-C was well tolerated with no discontinuations and no HIV transmissions. These data suggest that PrEP-C is a safe and effective option for serodiscordant couples wishing to conceive; a standardised protocol has been developed; data collection via a central database is under way.

Objective: The package of care to reduce HIV mother to child transmission (MTCT) has evolved significantly since trials of ante and intrapartum antiretroviral therapy (ART) in 1994. In the UK MTCT rate has fallen from 25.6% in the 1990s to 0.46%. We review the management of HIV in pregnancy in Brighton in the context of evolving guidelines. Study design: HIV, obstetric and neonatal notes of all HIV positive women, pregnant between 2003 and 2014, were reviewed. Results: 97 pregnancies in 75 women were identified, resulting in 79 live births. Antenatal HIV diagnosis was made in 22 (28%). The proportion of pregnancies in those with known HIV at conception increased over the time period. At conception 58 (60%) were on ART, 33 (57%) of who continued on their original regimen. 34 (35%) initiated ART following conception: 14 known to be HIV positive, 20 diagnosed during pregnancy. Two did not start ART (1 due to miscarriage, 1 as diagnosed post-delivery) and in three cases ART history was unavailable due to transfer to alternative centres. ART was initiated on average at 22 weeks gestation (range 6–34). 4(5%) received Zidovudine (AZT) monotherapy, all before 2006. Choice of combination ART (cART) varied with time reflecting changing guidelines. Prior to 2008 an AZT containing regimen was used in 83% versus 8% after. Planned mode of delivery was documented in 73: 30(41%) planned a normal vaginal delivery (NVD), 43(59%) a caesarean section (CS). The viral load (VL) was

Reduced bone mineral density is more common in HIV due to traditional and HIV-specific risk factors.1 Thirty-eight per cent of Brighton's HIV cohort is aged over 50; as they age, increased morbidity and mortality associated with fractures is likely. Fracture prevention must therefore be prioritised. FRAX assesses the 10-year risk of major osteoporotic fracture by modelling cohort data using 11 clinical risk factors, …

Recent advances in antiviral therapy have improved outcomes in HIV-positive individuals co-infected with hepatitis B and C virus (HBV/HCV). Our aim was to assess prevalence and predictors of chronic liver disease (CLD) due to the metabolic syndrome (MS), alcohol and antiretrovirals (ARVs) use in HIV-monoinfected individuals. This was a retrospective cohort study (2005–2012). HIV-positive patients with negative HBV/HCV serology and at least two elevated alanine aminotransferase (ALT) levels six months apart were included. Data are presented as mean ± SD or percentage. Despite negative viral serology, 27% (1047/3872) of HIV-positive individuals had persistently elevated ALT. Only 243 (23.2%) were investigated (by imaging in the majority, only 58 undergoing liver biopsy/transient elastography). CLD was identified in 66.2%, this being clinically significant in one in four individuals. Potential CLD risk factors were alcohol (44.2%), hepatotoxic ARVs (74.1%) and MS risk factors (68%) with 68.7% having >1 risk factor. On multivariate logistic regression analysis serum triglyceride (OR 1.482, 95% CI 1.053–2.086, p = .024) was the only independent predictor of CLD. Overall, 4.3% were referred to Hepatology services. In conclusion, less than 6% of HIV-monoinfected individuals with persistently elevated ALT undergo objective assessment of hepatic fibrosis. Despite non-stringent criteria, some degree of non-viral CLD is identified in approximately two-thirds of those investigated, risk factors being synonymous with those for the MS. This increasing yet under-recognised non-viral CLD burden warrants timely recognition to prevent long-term morbidity and mortality.

The overall purpose of these guidelines is to provide guidance on best clinical practice in the treatment and management of adults with HIV infection with antiretroviral therapy (ART). The scope includes: (i) guidance on the initiation of ART in those previously naive to therapy; (ii)support of patients on treatment; (iii) management of patients experiencing virological failure; and (iv) recommendations in specific patient populations where other factors need to be taken into consideration. The guidelines are aimed at clinical professionals directly involved with and responsible for the care of adults with HIV infection and at community advocates responsible for promoting the best interests and care of HIV-positive adults. They should be read in conjunction with other published BHIVA guidelines.

The overall purpose of these guidelines is to provide guidance on best clinical practice in the treatment and management of human immunodeficiency virus (HIV)-positive pregnant women in the UK. The scope includes guidance on the use of antiretroviral therapy (ART) both to prevent HIV mother-to-child transmission (MTCT) and for the welfare of the mother herself, guidance on mode of delivery and recommendations in specific patient populations where other factors need to be taken into consideration,such as coinfection with other agents. The guidelines are aimed at clinical professionals directly involved with, and responsible for, the care of pregnant women with HIV infection.

Reports have described a decrease in glomerular filtration rate (eGFR) associated with tenofovir disoproxil fumarate (TDF) use in HIV positive individuals. However, no study has examined renal function over a prolonged period in HIV/hepatitis B virus (HBV) co-infected patients. We assessed the long-term durability and toxicity of TDF in a cohort of 39 e antigen (eAg) positive co-infected patients commenced on TDF 245 mg daily either in addition to or as part of standard antiretroviral therapy. Immunological and virological parameters were followed to 260 weeks, with the median follow-up period being 251 weeks (range 69-290 weeks). eGFR was calculated using the Modification in Diet in Renal Disease equation. On treatment at 260 weeks, 88% (14/16) had HIV viral load

Tenofovir disoproxil fumarate (TDF) may cause renal tubular dysfunction (RTD) and reduce bone mineral density (BMD). We examined the relationship between RTD and BMD in TDF-exposed HIV-positive men.We analysed urinary retinol-binding protein/creatinine ratio (RBPCR) and fractional excretion of phosphate (FEPO4) to quantify RTD in a cross-sectional sample of randomly selected HIV-positive men at a single tertiary outpatient clinic. BMD at the lumbar spine and hip was measured by dual-energy X-ray absorptiometry. Multivariate logistic regression was used to analyse factors associated with RTD, and linear regression to examine the relationship between RTD and BMD.Of 293 men (mean age 48 years, 94% White ethnicity, median TDF exposure 2.1 years), 22.5% had RBPCR-defined RTD and 12.3% had FEPO4-defined RTD. We observed a negative correlation between RBPCR and BMD at the spine (β -0.2, P = 0.002) and hip (total: β -0.1, P = 0.02; femoral neck: β -0.1, P = 0.02), but not between FePO4 and BMD. In multivariable analyses, RTD defined by more than five-fold elevations in RBPCR was associated with significantly lower BMD of the spine.In HIV-positive patients receiving TDF-containing antiretroviral therapy, RTD was associated with lower BMD of the spine in HIV-positive men. RBPCR quantification may identify patients at increased risk of TDF-associated BMD loss.

OBJECTIVE To evaluate treatment outcome of acute hepatitis C virus (HCV) in HIV-positive individuals. DESIGN Open-label, prospective study conducted in London, January 1997-December 2003. METHODS Patients in whom acute HCV infection had been diagnosed had sequential HCV RNA levels measured at 0, 4, 12, 24, 32, and 48 weeks. If HCV RNA positive at 12 weeks, patients were offered pegylated interferon alpha-2b 1.5 microg/kg/wk and ribavirin 800-1200 mg/d for 24 weeks. Patients with increasing HCV RNA titers were offered treatment earlier. RESULTS Fifty male homosexuals with a mean age 37 years were identified: 44 from abnormal liver function test results, 4 from sexual contact with an HCV-positive partner, and 2 at HIV seroconversion. Overall, 12 individuals became HCV RNA negative spontaneously. This was significantly associated with high baseline median CD4(+) count (P = 0.029), CD4(+) count >500 cells/mm(3) (P = 0.017), and lower HCV RNA titers (P = 0.017). Only 27 patients accepted treatment, 16 (59%) of whom reached sustained virologic response. This was associated with higher peak mean alanine aminotransferase (P < 0.001) and higher baseline CD4% (P = 0.041). CONCLUSIONS Sustained virologic response rates in HIV-positive patients treated for acute HCV infection are lower than in HIV-negative subjects. Because a high percentage of individuals seroconvert spontaneously, treatment should be delayed until after 12 weeks.

We report a case of acute kidney injury due to primary renal diffuse large B-cell lymphoma, which developed after initiation of tenofovir-containing antiretroviral therapy in a 28-year-old HIV-positive man.

Introduction : Combination antiretroviral therapy (cART) may affect vitamin D [25(OH)D], parathyroid hormone (PTH), bone mineral density (BMD) and bone turnover (BT). Reduced BMD and secondary hyperparathyroidism have been reported with tenofovir (TDF). We investigated the associations between TDF and bone markers, especially in 25(OH)D-deficient patients. Materials and Methods : In a single-centre longitudinal study investigating BMD in HIV-positive men, serum 25(OH)D, calcium, phosphate, PTH and alkaline phosphatase (ALP) were measured. Lumbar spine, non-dominant total hip and non-dominant femoral neck BMD (g/cm 2 ) were measured using dual-energy X-ray absorptiometry. BT was assessed by serum type 1 procollagen (P1NP) and carboxy-terminal collagen cross-links (CTX). Mann–Whitney U tests compared serum markers and BT, and t-tests compared BMD according to TDF in all and 25(OH)D-deficient patients. Results : A total of 422 men were recruited: mean age 47 (SD 9.8) years, 94% white ethnicity, 93% MSM, diagnosed HIV positive for median 9.6 (IQR 5.0,15.5) years, median CD4 547 (IQR 411,696) cells/µL, HIV RNA 75), insufficient (50–75), deficient (25–50) and severely deficient (

OBJECTIVES To evaluate the prevalence, impact, and risk factors for pain among a cohort of human immunodeficiency virus (HIV)-infected adults treated with combination antiretroviral therapy if indicated according to current guidelines. METHODS This was a cross-sectional epidemiological observational study. All patients attending 1 HIV-outpatient center in the United Kingdom in a 10-month period were eligible. Patients completed a validated questionnaire enquiring about demographics, HIV factors, and symptoms of pain. RESULTS Of 1050 eligible participants, 859 (82%) completed a questionnaire. The 1-month period prevalence of pain lasting >1 day was 62.8% among whom 63% reported current pain. The prevalence of pain at most anatomic sites was broadly similar to that observed in population studies using the same questionnaires except that we found considerably higher rates of foot/ankle pain. The median duration of pain was 3 years (range, 0 to 51 y) and the median pain score was 5.0 on an 11-point visual analogue score. Over 40% of people in pain had consulted their primary care physician and >20% were taking analgesics daily. Independent risk factors for current pain were older age (P=0.001), time since diagnosis of HIV infection (P=0.001), and receipt of a protease inhibitor-based regimen (P=0.04). DISCUSSION Pain, and notably foot/ankle pain, is common among adults living with prevalent HIV and is associated with substantial morbidity and health care utilization.

Summary There is growing awareness that HIV infection is associated with low bone mass and fracture. DXA is a relatively scarce resource. Therefore, we evaluated two tools: peripheral DXA (pDXA) at the forearm and Fracture Risk Assessment Tool (FRAX®) to see which performed best at identifying men who should undergo DXA. In this setting, neither pDXA nor FRAX® showed good sensitivity and specificity for DXA. Purpose Infection with human immunodeficiency virus (HIV) is associated with an increased risk of low bone mineral density (BMD) and fractures. European guidance advocates screening using the FRAX® tool at diagnosis, on initiation of antiretroviral therapy and biannually thereafter in order to decide the need for DXA scanning. This cross-sectional study evaluates the performance of FRAX® and compares its sensitivity and specificity with that of another screening tool, peripheral forearm DXA (pDXA). Methods HIV-infected men with varying exposure to antiretroviral therapies were recruited. FRAX® scores were calculated for all participants and everybody underwent pDXA scanning. Femoral neck and lumbar spine BMD was acquired on a Hologic QDR machine by an assessor blinded to the results of the FRAX® and pDXA. Results One hundred and sixty-eight men (median age 45 years) were recruited with a median duration since HIV diagnosis of 74 months. In total, 21 % of subjects had either osteoporosis (aged ≥50 years) or BMD lower than expected for age (aged

We report here the first two cases of hepatobiliary pathology in HIV-positive men following recreational use of ketamine: >1 g/day over a 12-month period while on ritonavir-based antiretroviral therapy. Presentation in each case was acute with nausea, vomiting and epigastric pain. Alanine aminotransferase was raised at 3.2× and 10.1 × upper limit of normal and alkaline phosphatase was raised at 1.7× and 2.5 × ULN for cases 1 and 2, respectively. Magnetic resonance cholangiopancreatography showed dilatation of the common bile duct; case 1, 18 mm and case 2, 14 mm with no ductal obstruction on endoscopic retrograde cholangiopancreatography. The symptoms resolved, common bile duct dilatation and liver function improved on discontinuation of ketamine use. Time to development of symptoms is shorter than reported in HIV-negative cases (12 months vs. 4 years) which may be explained by an interaction between ketamine and ritonavir.

Rates of osteoporosis and fracture may be increased in HIV but there are few UK data. Our aim was to examine the prevalence of and risk factors for osteoporosis and fractures among a homogeneous cohort of well-characterized HIV-infected men. In total, 168 men were recruited, median age 45 years, 37 combination antiretroviral therapy (cART) naïve, 46 with 10 years). All participants provided information on bone health and underwent DEXA scanning. Osteopenia was found in 58% of subjects and osteoporosis in 12%; 14% reported fractures since HIV diagnosis. Number of fractures since HIV diagnosis was significantly increased among those with osteoporosis (OR 3.5, 95% CI 1.2–10.4, p = 0.018). Duration of infection greater than 13 years was significantly associated with osteoporosis. Duration of cART was associated in univariate but not multivariate analyses. Strategies to prevent osteoporosis and fractures in HIV will require attention to viral and lifestyle factors and not just cART.

Background/introduction Gender plays an important role in determining vulnerability and ability to access appropriate HIV care. Services must adapt to meet the needs of their population. Our HIV outpatient service provides care for 2400 people: Methods A pilot plus follow up patient survey of the women attending the HIV outpatients. Results 16 women completed the pilot questionnaire; 5/16 (31.2%) aged 17–45 years, 11/16 (68.75%) aged > 46. 4/16 (25%) disclosed a disability. 16/16 (100%) had no difficulty accessing our service. 3/16 (18.8%) of households had children living in them Discussion/conclusion Preliminary results suggest that that the women attending our clinic have no issues with child care, language barriers or disabilities. Women over 45 years were more likely to take part in our study (70% response). Of concern is a reported lack of knowledge about services already available which we are pursuing.

There are international minimum standards for provision of sexual and reproductive health (SRH) care in a crisis situation (MISP).1 The new migrant ‘jungle’ camp in Calais, France, has been increasing in size.2 There are increasing numbers of young women.2 Historically, there has been limited non-governmental organisation (NGO) input and multiple small grassroots volunteer groups have emerged. As part of a charity assessment exercise, we interviewed volunteer …

BACKGROUND HAART dramatically reduces mother-to-child transmission of HIV allowing vaginal delivery if the viral load is low. This study provides data for the optimum timing of short-term HAART in pregnancy. METHODS Retrospective multicentre cohort study of pregnant women commencing HAART in London and Brighton, UK. Demographics, gestation, drug class, CD4 cell count, and viral load results were collated. Survival curves for reaching a viral load less than 50 copies/ml were stratified by initial HIV viral load. Cox's proportional hazards regression model was adjusted for demographics and immunovirological parameters. RESULTS Viral load was less than 50 copies/ml in 292 of 378 pregnancies (77.2%) by delivery. Pretreatment viral load was associated with the time taken, and the proportion achieving a viral load less than 50 copies/ml at (P≤0.001). When baseline viral load was less than 10 ,000 copies/ml, gestational age at HAART initiation did not affect success up to 26.3 weeks gestation. When viral load was more than 10 ,000 copies/ml, deferring HAART past 20.4 weeks reduced the probability of reaching less than 50 copies/ml by delivery (P=0.011). When baseline viral load was more than 100, 000 copies/ml the likelihood of reaching a viral load of less than 50 copies/ml was low (37%: hazard ratio 0.31), and dependent on the length of time on HAART. The hazard ratio for a nonnucleoside reverse transcriptase inhibitor regimen achieving a viral load less than 50 copies/ml compared with a protease inhibitor was 0.7 (95% confidence interval 0.52-0.94). CONCLUSION With a viral load more than 10, 000 copies/ml and especially with a viral load more than 100 ,000 copies/ml, the probability of achieving either less than 50 copies/ml by the time of delivery is compromised by delaying initiation of short-term highly active antiretroviral therapy beyond 20.4 weeks gestation. Current UK and other guidelines for when to commence START may therefore limit the chance of vaginal delivery.

Objective We recently showed that a urine albumin/total protein ratio (uAPR) 30 mg/mmol) into two groups: those with predominantly ‘tubular’ proteinuria (TP) (uAPR

Background/introduction Hepatitis E Virus (HEV) is increasing in incidence. Transmission routes include faecal-oral, blood and zoonotically. Patients present with no symptoms; elevated liver enzymes; acute/chronic hepatitis and/or neuropathy. Evidence suggests poorer outcomes among HIV+ patients. Aim(s)/objectives To describe known cases of HEV/HIV co-infection within a cohort of 2200 HIV+ patients. Methods We present two cases. Results Patient-1, a 63-year-old asymptomatic MSM with a 22-year history of HIV, recently re-started Truvada/darunavir/ritonavir: CD4 393(17%) cells/mm 3 and HIV VL 327,824 copies/ml. Routine bloods identified newly elevated ALT 477 IU/L: other liver function, clotting and liver ultrasound were normal. He had no STIs diagnosed in the preceding year nor risk factors for HEV. A hepatitis screen was performed. HEV IgG, IgM and PCR were positive. Treatment was supportive, with normalisation of ALT and negative HEV-PCR after eight weeks. Patient-2, a 41-year-old asymptomatic MSM with an 11-year history of HIV was ART naive: CD4 682(25%) cells/mm 3 and HIV VL 13,109 copies/ml. Routine bloods identified newly elevated ALT 459 IU/L: other liver function, clotting and liver ultrasound were normal. He had no STIs diagnosed in the preceding year nor risk factors for HEV. Although HEV serology was initially equivocal, IgG and IgM later became positive with detectable PCR. His ALT normalised and HEV-PCR became undetectable four weeks later. Discussion/conclusion HEV appears to be a self-limiting-asymptomatic illness in HIV+ MSM with good CD4 counts. HEV may be sexually transmitted in populations with increasing STI rates. HEV should be considered a potential cause of elevated liver enzymes in HIV+ patients.

Purpose of review This review aims to summarize recent developments in the epidemiology and management of sexually transmitted infections in HIV positive individuals. It will also discuss briefly the legal aspects of disclosure in relation to HIV transmission. Recent findings There has been a dramatic increase in the reported number of cases of syphilis globally in recent years. In the United Kingdom this has mainly been observed among HIV positive men who have sex with men (MSM). Since 2003 there have been a series of outbreaks of lymphogranuloma venereum reported in several European cities occurring mostly in HIV positive MSM. Sexual transmission of hepatitis C is increasing and appears to be more common in HIV positive MSM. Legal issues regarding HIV transmission have also come to the fore becoming an important part of the discussion of sexual health with an HIV positive patient. Summary Increases in sexually transmitted infection among HIV positive individuals suggest a worrying lack of adherence to safe sex guidelines and needs to be addressed urgently. The transmission of HIV is facilitated by the presence of certain sexually transmitted infections. Management of sexual health is an essential part of HIV care. (authors)

Although the principal mode of hepatitis C (HCV) transmission in the United Kingdom is injecting drug use (IDU), the risk for a third of infections is unknown.1 The contribution of sexual transmission between men who have sex with men (MSM) to the spread of hepatitis C is unclear, however evidence is accumulating that both co-infection with HIV2 and the presence of other sexually transmitted infections (STIs) facilitate sexual transmission of HCV.3 With the reported increases in unsafe sex and STIs in HIV positive MSM we questioned whether these circumstances may lead to an increase in the number of HCV infections. This study was undertaken to determine whether within our clinics, changes in the number of individuals being diagnosed with acute HCV infection were occurring and to ascertain risk factors for acquisition in these individuals. A case note review of all patients within the HIV and sexual health clinics of St Stephen’s Centre with diagnosed acute HCV infection between January …

Objectives There is increasing in vitro and in vivo evidence that reduced zidovudine (ZDV) susceptibility is generated by the selective pressure conferred by other nucleoside reverse transcriptase inhibitors (NRTIs). However, the degree to which this occurs in clinical practice remains unclear. We assessed phenotypic and genotypic resistance in ZDV-naive patients with virological failure on stavudine (d4T)-containing regimens, with particular reference to potential cross-resistance between d4T and ZDV. Methods Patients were identified from a clinical database. Treatment history was confirmed by case note evaluation and discussion with patients. Genotypic and phenotypic analyses were undertaken by Virco (Virco BVBA, Mechelen, Belgium). Results Sixty-seven drug-experienced, ZDV-naive patients who underwent a resistance test while failing a d4T-containing regimen were identified. Of these patients, 23% had received three or more NRTIs and 42% at least one non-nucleoside reverse transcriptase (RT) inhibitor; 22% had viruses with reduced d4T susceptibility (>1.8-fold resistance), and 25% had viruses with reduced ZDV susceptibility (>4-fold). The most frequently observed RT mutations were identified. A significant correlation was found between susceptibility to d4T and susceptibility to ZDV (r=0.36; P=0.003), and also between virtual resistance to d4T and that to ZDV (r=0.38; P=0.002). Conclusions A significant minority of d4T-treated, ZDV-naive patients were found to have viruses with reduced ZDV susceptibility, with a variable association with classical ZDV resistance mutations. These data suggest that cross-resistance between d4T and ZDV may involve novel constellations of mutations. Correlations between d4T and ZDV susceptibilities and resistances further support cross-resistance between NRTIs.

BACKGROUND\ud \ud Initiating therapy with a low CD4 cell count is associated with a substantially greater risk of disease progression and death than earlier initiation. We examined factors associated with late presentation of HIV using the new European consensus definition (CD4 cell count