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Objectives: As people with HIV (PWH) age, the prevalence of frailty increases. Rapid screening tests to identify frailty within HIV outpatient settings are required to identify at‐risk individuals. We undertook a service evaluation to assess three short frailty assessments in PWH. Methods: We assessed two objective [gait speed (GS), timed‐up‐and‐go test (TUGT)] and one subjective [the self‐reported health questionnaire (SRH)] frailty screening tools in PWH aged > 40 years attending a single HIV outpatient department. Factors associated with positive frailty screening tests (defined as GS < 0.8 m/s, TUGT ≥ 10 s and SRH score < 6) were assessed using logistic regression models. Ethical considerations: This was a service evaluation and was approved as a service evaluation by the Imperial College Healthcare NHS trust HIV clinical research committee (February 2020). All participants were given verbal information and were able to terminate the screening tests at any time. Results: Of 84 PWH approached, 80 individuals completed all screening tests (median age = 56 years, range: 40–80) with a positive frailty screening prevalence in 19%, 33% and 20% for GS, TUGT and SRH, respectively. All tests were considered acceptable to participants. Factors statistically significantly associated with frailty included age (GS and TUGT), detectable HIV RNA (TUGT), number of comorbidities (GS and TUGT), presence of polypharmacy (GS and TUGT) and total number of concomitant medication (GS and SRH). Conclusions: Rates of positive screening tests for frailty are dependent on screening tool used, with all three tools being acceptable to participants. Objective measures of frailty screening (GS and TUGT) are more closely associated with clinical parameters than is a subjective measure of frailty screening (SRH). [ABSTRACT FROM AUTHOR]

Objectives: The aim of the study was to investigate whether lamivudine (3TC) or emtricitabine (FTC) use following detection of M184V/I is associated with better virological outcomes. Methods: We identified people with viruses harbouring the M184V/I mutation in UK multicentre data sets who had treatment change/initiation within 1 year. We analysed outcomes of viral suppression (< 200 HIV‐1 RNA copies/mL) and appearance of new major drug resistance mutations (DRMs) using Cox and Poisson models, with stratification by new drug regimen (excluding 3TC/FTC) and Bayesian implementation, and estimated the effect of 3TC/FTC adjusted for individual and viral characteristics. Results: We included 2597 people with the M184V/I resistance mutation, of whom 665 (25.6%) were on 3TC and 458 (17.6%) on FTC. We found a negative adjusted association between 3TC/FTC use and viral suppression [hazard ratio (HR) 0.84; 95% credibility interval (CrI) 0.71–0.98]. On subgroup analysis of individual drugs, there was no evidence of an association with viral suppression for 3TC (n = 184; HR 0.94; 95% CrI 0.73–1.15) or FTC (n = 454; HR 0.99; 95% CrI 0.80–1.19) amongst those on tenofovir‐containing regimens, but we estimated a reduced rate of viral suppression for people on 3TC amongst those without tenofovir use (n = 481; HR 0.71; 95% CrI 0.54–0.90). We found no association between 3TC/FTC and detection of any new DRM (overall HR 0.92; 95% CrI 0.64–1.18), but found inconclusive evidence of a lower incidence rate of new DRMs (overall incidence rate ratio 0.69; 95% CrI 0.34–1.11). Conclusions: We did not find evidence that 3TC or FTC use is associated with an increase in viral suppression, but it may reduce the appearance of additional DRMs in people with M184V/I. 3TC was associated with reduced viral suppression amongst people on regimens without tenofovir. [ABSTRACT FROM AUTHOR]

Objectives: Persistent CD4:CD8 ratio inversion (< 1) is associated with mortality in older people. We investigated the interaction of the effects of baseline CD8 count and age at HIV diagnosis on CD4:CD8 ratio recovery with antiretroviral therapy (ART). Methods: An observational study (1 January 2007 to 31 December 2016) was carried out using routinely collected data from the HIV outpatient services at Imperial College Healthcare NHS Trust, London, UK. CD4 and CD8 counts, prior to and during ART, treatment during primary HIV infection (PHI) and HIV‐1 viral load were included in univariate and multivariate analyses using Cox proportional hazard regression. Results: Data were included for 876 patients starting ART, where HIV suppression was achieved. Of these patients, 741 of 876 (84.6%) were male and 507 of 876 (57.9%) were Caucasian. The median time on ART was 38 [interquartile range (IQR) 17–66] months. CD8 count change on ART was bidirectional; low CD8 counts (≤ 600 cells/μL) increased and high CD8 counts (> 900 cells/μL) decreased. The median pre‐ART CD4:CD8 ratio was 0.41 (IQR 0.24–0.63), and recovery (≥ 1) occurred in 274 of 876 patients (31.3%). Pre‐ and post‐ART CD4:CD8 ratios were lower in those aged > 50 years compared with young adults aged 18–30 years (P < 0.001 and P = 0.002, respectively). After adjustment, younger age at HIV diagnosis (P < 0.001) and treatment during PHI (P < 0.001) were favourable for CD4:CD8 ratio normalization. Conclusions: Older age (> 50 years) at HIV diagnosis was associated with persistent CD4:CD8 ratio inversion, whereas treatment of PHI was protective. These findings confirm the need for testing and early treatment of people aged > 50 years, and could be used in a risk management algorithm for enhanced surveillance. [ABSTRACT FROM AUTHOR]

The article discusses a study related to description of the clinical experience of the off-licence use of Maraviroc (MVC) one-daily prescribed on the recommendation of a regional paediatric virtual clinic (PVC) for prenatally infected adolescents and children. Topics include off-licence use occurred in a small number of children but to date description for only twice-daily use, adolescent stopping use due to gastrointestinal toxicity and treatment-related side effects mostly gastrointestinal.

Introduction: Long-acting injectable cabotegravir + rilpivirine (CAB + RPV LAI) was approved for use in virally suppressed adults in the England and Wales national health service in November 2021. We describe a service evaluation of delivery processes and outcomes in 12 clinics., Methods: Centres populated a database using information from local policies and clinical records. Services were asked to describe approval processes, clinic pathways, and adherence to national guidelines. Additional data were collected on reasons for regimen choice, treatment discontinuations, and management of viraemia., Results: In total, 518 adults from 12 clinics were approved for CAB + RPV LAI between February 2022 and December 2023. Of the 518 people approved for CAB + RPV LAI, 423 received at least one injection. Median duration on CAB + RPV was 7.5 months (interquartile range 3.7-11.3). In total, 97% of injections were administered within the ±7-day window. Virological failure occurred in 0.7%, and 6% discontinued CAB + RPV., Conclusion: In this large UK-based cohort, robust approval processes and clinic protocols facilitated on-time injections and low rates of both discontinuation and virological failure., (© 2024 The Author(s). HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

The Conference on Retroviruses and Opportunistic Infections (CROI) is usually the most significant HIV conference of the year in terms of basic and clinical scientific output. CROI 2024 in Denver, USA, felt very much back to 'business as usual' following COVID-19 disruptions that had impacted preceding years, but also felt more global and outward- facing. The British HIV Association supports a working group to attend CROI annually and deliver feedback in the UK. This article summarizes the highlights from that meeting., (© 2024 British HIV Association.)

Contemporary antiretroviral therapy (ART) regimens have high barriers to the development of drug resistance. However, resistance to earlier antiretrovirals and uncommon cases of resistance to contemporary ART illustrate the continued need for good clinical management of HIV drug resistance. Here, we describe HIV drug-resistance mechanisms, the interaction of HIV drug-resistant mutations and the patterns of drug resistance to contemporary ART. We then provide guidance on the management of HIV drug resistance, including how to limit the development of resistance and manage virologic failure that is complicated by resistance. To complement this, links to resources and treatment guidelines are provided that can assist with the interpretation of HIV drug resistance test results and optimal ART selection in the clinic.

Objectives: In response to the COVID-19 pandemic, HIV outpatient attendances were restricted from March 2020, resulting in reduced frequency of HIV viral load (VL) monitoring (previously 6-monthly) in clinically stable and virologically suppressed people living with HIV (PLWH). We investigated virological outcomes during this period of reduced monitoring and compared with the previous year, prior to the COVID-19 pandemic., Methods: People living with HIV with undetectable VL (<200 HIV RNA copies /mL) on antiretroviral therapy (ART) were identified from March 2018 to February 2019. We determined VL outcomes during the pre-COVD-19 period (March 2019-February 2020) and the COVID-19 period (March 2020-February 2021) when monitoring was restricted. Frequency and longest durations between VL tests in each period were evaluated, and virological sequelae in those with detectable VL were determined., Results: Of 2677 PLWH virologically suppressed on ART (March 2018-February 2019), VLs were measured and undetectable in 2571 (96.0%) and 2003 (77.9%) in the pre-COVID and COVID periods, respectively. Mean (SD) numbers of VL tests were 2.3 (1.08) and 1.1 (0.83) and mean longest duration between VL tests was 29.5 weeks (SD 8.25, 3.1% were ≥12 months) and 43.7 weeks (12.64, 28.4% were ≥12 months), in the pre-COVID and COVID periods, respectively. Of 45 individuals with one or more detectable VL during the COVID-19 period, two developed new drug resistance mutations., Conclusion: Reduced VL monitoring was not associated with poorer virological outcomes in the majority of stable individuals receiving ART. One in 20 individuals had not returned for VL testing after ≥31 months and the risk of harm in these individuals is unknown., (© 2023 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Objective: Our objectives were to investigate the recent frequency of cerebrospinal fluid (CSF) HIV RNA escape and other CSF viral nucleic acid detection in people with HIV with neurological symptoms and to assess associated clinical factors., Method: This was a retrospective cohort analysis of people with HIV who underwent CSF examination for clinical indications between 2017 and 2022. Individuals were identified from pathology records, and clinical data were recorded. CSF HIV RNA escape was defined as CSF HIV RNA concentrations greater than in plasma. CSF viral screen included herpes simplex virus types 1 (HSV-1) and 2 (HSV-2), varicella zoster virus (VZV), Epstein Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 6 (HHV-6) and JC virus. When cases were detected in five or more people with HIV, associated clinical factors were assessed using linear regression modelling., Results: CSF HIV RNA escape was observed in 19 of 114 individuals (17%) and was associated with the presence of HIV drug resistance mutations and non-integrase strand transfer inhibitor-based antiretroviral therapy (p < 0.05 for all) when compared to people with HIV without escape. Positive viral nucleic acid testing included EBV (n = 10), VZV (3), CMV (2), HHV-6 (2) and JC virus (4). Detectable CSF EBV was not considered related to neurological symptoms and was associated with concomitant CSF infections in eight of ten individuals and with CSF pleocytosis, previous AIDS, lower nadir and current CD4 T-cell count (p < 0.05 for all)., Conclusion: In people with HIV with neurological symptoms, the frequency of CSF HIV RNA escape remains similar to that in historical reports. Detectable EBV viral nucleic acid in the CSF was observed frequently and, in the absence of clinical manifestations, may be a consequence of CSF pleocytosis., (© 2023 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

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) < 50 copies/mL. Median FSH was 65.9 mIU/mL (IQR: 49.1-78.6). Only four women (4.7%) had FSH ≤ 30 mIU/mL; none reported smoking or drug use, all had CD4 T-cell count ≥ 200 cells/μL, and one had viral load (VL) ≥ 50 copies/mL. Median body mass index (BMI) was elevated compared with women with FSH > 30 mIU/mL (40.8 vs. 30.5 kg/m 2 ). 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/m 2 . 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., (© 2021 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Contact tracing is central to the public health response to COVID-19, but the approach taken has received criticism for failing to make enough of an impact on disease transmission. We discuss what can be learned from contact tracing in other infections, and how the natural history of COVID-19 should shape the strategies used., (© Royal College of Physicians 2021. All rights reserved.)

Following changes in national antiretroviral therapy (ART) guidelines removing the CD4 threshold for initiation of ART, we evaluated the time to ART initiation and reasons for delayed or non-initiation. A retrospective notes review of 292 newly diagnosed HIV-positive individuals attending two London clinics between August 2015 and December 2016 was performed. Two hundred and fifty-four of 292 (87%) individuals started ART. Median time to ART initiation was 29 days (range: 0-514). Thirty of 292 (13%) did not start ART. Rates of virological suppression at six months were similar regardless of time to ART initiation. People who inject drugs (16.7% vs. 3.6%) (p = 0.009), having a higher median baseline CD4 cell count (500 vs. 388 cells/mm 3 , p = 0.001), and having gastrointestinal/liver co-morbidities (23% vs. 9%, p = 0.001) were associated with delayed ART initiation. The cohort not on ART had a higher median baseline CD4 cell count (500 vs. 388 cells/mm 3 , p < 0.001). Documented reasons for delayed or ART non-initiation included patient's choice, prolonged adjustment periods, and difficulty leaving work. We conclude that delayed or non-initiation of ART was associated with injecting drug use and prolonged adjustment to a new HIV diagnosis. Clinician factors may include lack of urgency with higher baseline CD4 cell counts. Improved linkage to care and drug services pathways may encourage timely ART initiation.

Objectives: Retrospective analysis of evolution of HIV tropism and association with disease progression in perinatal HIV-1 infection (PaHIV)., Methodology: Eligible patients with PaHIV were grouped as slow, rapid or long-term non-progressors (LTNP). The V3 region of gp120 was sequenced from stored plasma samples and tropism determined by geno2pheno algorithm (FPR 5.75%). Logistic regression with generalised estimating equations assessed factors associated with R5 virus. Time to tropism change was assessed using standard survival methods., Results: At baseline (n=48) median age was 12 years (IQR 9.3-14.8), 52% were female, 79% were Black African, 96% were non-B subtypes and 81% (39/48) had R5-using virus. Median follow-up was 7.7 years (308.6 person-years), with a median of five (range 1-14) samples per subject (total 252). Analysing all samples, R5 virus was associated with higher current CD4 cell count (median 520 cells/mm(3) R5 vs 202 for X4, P=0.0005), LTNP (35% vs 11%, P=0.05), non-Black ethnicity (74% vs 89%, P=0.05) and female gender (55% vs 28%, P=0.005). Twelve of 38 (31%) with R5 virus at baseline switched to X4/dual-using virus, with an estimated 5-year risk of switch of 24.4% (95% CI 9.7-39.2%) predicted by lower current CD4 cell count (unadjusted HR 0.62/50 cells higher, 95% CI 0.47-0.81, P=0.0006). Eleven of 19 (58%) with X4/dual-using virus subsequently had R5 virus at one or more time points., Conclusion: Maraviroc was a treatment option for 81% at 12 years, falling to 56% at 18 years, with lower CD4 cell count predictive of co-receptor switching. Paediatric studies of CCR5 antagonists should be expedited to ensure they are an early treatment option before tropism switching occurs.

Objective: The objective of this study is to review clinical outcomes of recommendations made by a multidisciplinary paediatric virtual clinic (PVC) for complex case management of paediatric HIV as a model of care within a tertiary network., Design: A retrospective review of the clinical outcomes of paediatric and adolescent (0-21 years) referrals to the PVC at St. Mary's Hospital, Imperial College Healthcare NHS Trust, London was performed between October 2009 and November 2013., Results: 234 referrals were made for 182 children from 37 centres, discussed in 42 meetings (median age 13 years, IQR 10-15 years). Reasons for referral included virological failure (44%), simplification of the current regimen (24%) and antiretroviral drug complications (24%). At latest follow-up, PVC advice had been instituted in 80% of referrals. Suppression following virological failure was achieved in 48% following first referral and 57% following subsequent discussions and was maintained in 95% of children referred for regimen simplification. Following advice, dyslipidaemia resolved in 42% and liver function normalised in 73% with biochemical hepatitis. Adherence support aided resolution of viraemia in nine children and 12% of referrals resulted in additional support, including psychology, social services and mental health input., Conclusions: Combined multidisciplinary virtual input with adult expertise in resistance and newer agents, paediatric knowledge of pill swallowing, childhood formulations/weight banding and parental support, assists complex treatment decision making in paediatric HIV infection. The Virtual Clinic model could be applied to the management of other rare complex diseases of childhood within a clinical network., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

End-stage kidney disease (ESKD) is a major complication of HIV infection. We observed a 3.8-fold increase in ESKD prevalence among black patients in the UK CHIC cohort during the 12-year study period. As of 2005, 107 patients had an ESKD diagnosis, 69 of whom (64%) were considered suitable for kidney transplantation (KT) and 34 (32%) had received a KT. Survival was similar for KT recipients and those awaiting KT (85% and 89% at 5 years, respectively; P = 0.53). Our results endorse the use of KT to manage ESKD in HIV-positive patients.

Objectives: Pharmacokinetic parameters following modifications to antiretroviral therapy and sanctuary site exposure are often unknown for recently licensed antiretrovirals. We assessed plasma, CSF and seminal plasma (SP) exposure of rilpivirine after switching from nevirapine., Methods: HIV-infected male subjects receiving tenofovir/emtricitabine/nevirapine (245/200/400 mg) once daily switched to tenofovir/emtricitabine/rilpivirine (245/200/25 mg) once daily for 60 days when CSF and semen samples were collected. Mean and individual plasma concentrations of nevirapine and rilpivirine were compared with the proposed plasma target concentration for nevirapine (3000 ng/mL) and the protein binding-adjusted EC90 for rilpivirine (12.1 ng/mL). Mean rilpivirine CSF and SP concentrations were calculated and individual values compared with the EC50 and EC90 for wild-type virus (0.27 and 0.66 ng/mL, respectively)., Results: Of 13 subjects completing study procedures including CSF examination, 8 provided seminal samples. By day 3, the mean plasma rilpivirine trough concentration was 29.7 ng/mL (95% CI: 23.8-37). No patient presented rilpivirine plasma concentrations under the proposed threshold. The mean rilpivirine concentration in CSF was 0.8 ng/mL (95% CI: 0.7-1.0), representing a CSF : plasma ratio of 1.4%, with concentrations above the EC90 in 85% (11/13) of patients. In SP, the mean rilpivirine concentration was 4.9 ng/mL (95% CI: 3.3-7.2), representing an SP : plasma ratio of 9.5%, with all concentrations above the EC90., Conclusions: Switching from nevirapine- to rilpivirine-containing antiretroviral therapy was safe and well tolerated, with plasma rilpivirine concentrations above the protein binding-adjusted EC90 in all subjects. Rilpivirine concentrations were always above the EC50 in the CSF and the EC90 in SP., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Objective: HIV-1 genetic variability may influence antiretroviral therapy (ART) outcomes. The study aim was to determine the impact of polymorphisms in regions known to harbor major nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations (codons 90-108, 135-138, 179-190, 225-348) on virologic responses to first-line NNRTI-based ART., Methods: Reverse transcriptase sequences from ART-naive individuals who commenced efavirenz (EFV) or nevirapine (NVP) with at least two nucleos(t)ide reverse transcriptase inhibitors (NRTIs) without major drug resistance mutations were analyzed. The impact of polymorphisms on week 4 viral load decrease and time to virologic failure was measured over a median 97 weeks., Results: Among 4528 patients, most were infected with HIV-1 subtype B (67%) and commenced EFV-based ART (84%). Overall, 2598 (57%) had at least one polymorphism, most frequently at codons 90, 98, 101, 103, 106, 135, 138, 179, and 238. Virologic failure rates were increased in patients with two (n = 597) or more than two (n = 72) polymorphisms [adjusted hazard ratio 1.43; 95% confidence interval (CI) 1.07-1.92; P = 0.016]. Polymorphisms associated with virologic failure occurred at codons 90 (mostly V90I), 98 (mostly A98S), and 103 (mostly K103R), with adjusted hazard ratios of 1.78 (1.15-2.73; P = 0.009), 1.55 (1.16-2.08; P = 0.003), and 1.75 (1.00-3.05: P = 0.049), respectively. Polymorphisms at codon 179, especially V179D/E/T, predicted reduced week 4 responses (P = 0.001) but not virologic failure., Conclusion: The occurrence of multiple polymorphisms, though uncommon, was associated with a small increase in the risk of NNRTI treatment failure; significant effects were seen with polymorphisms at codon 90, 98, and 103. The mechanisms underlying the slower suppression seen with V179D/E/T deserve further investigation.

We report the first published case of integrase inhibitor resistance in the central nervous system compartment in the absence of evidence of integrase inhibitor resistance in the plasma of a patient without human immunodeficiency virus (HIV)-encephalitis in the context of other HIV-associated central nervous system infections.

Background: Cerebrospinal fluid (CSF) HIV RNA load may be associated with central nervous system (CNS) disease in HIV infected subjects. We investigated parameters associated with CSF HIV RNA within a large clinical cohort., Methods: All HIV infected subjects undergoing CSF examination including assessment of CSF HIV RNA at St. Mary's Hospital, London, UK between January 2008 and October 2010 were included. Parameters associated with a detectable CSF HIV RNA load were assessed using linear regression modelling. CSF viral escape was defined as CSF RNA >0.5 log(10) copies/mL greater than plasma HIV RNA and >200 copies/mL where plasma HIV RNA <50 copies/mL., Results: Of 142 subjects, 99 were receiving antiretroviral therapy (ART). Plasma HIV RNA was <50 copies/mL in 69 subjects. CSF examination was performed for investigation of presumed HIV encephalopathy (IxHE, n = 57), other CNS diseases considered HIV related (n = 39), syphilis (n = 20) and CNS presentations not considered HIV related (n = 26). CSF viral escape was present in 30/142 (21%) subjects overall and in 9/69 (13%) of those on ART with undetectable plasma HIV RNA. Overall, plasma HIV RNA load was significantly associated with detectable CSF HIV RNA (p ≤ 0.001). In subjects with plasma HIV RNA <50 copies/mL, only CNS penetration effectiveness (CPE, 2008) score of <2 was significantly associated with detectable CSF HIV RNA (p = 0.044). In patients undergoing LP for IxHE both plasma HIV RNA and CPE scores were independently associated with detectable CSF HIV RNA (p = 0.019 & 0.003 respectively) which was not observed in subjects undergoing CSF examination for other medical reasons., Conclusions: In a clinical setting, CSF viral escape is observed frequently in 21% of subjects and is associated with different parameters depending on the clinical scenario., (Copyright © 2012 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

CXCR4-tropic (X4) HIV-1 variants are associated with faster disease progression compared with CCR5-tropic variants; however, the mechanism for this is unclear. We measured T-cell activation in 120 individuals with primary HIV-1 infection. X4-utilizing variants, determined genotypically, were present in 8.3% of the participants and were associated with higher levels of CD4 T-cell activation, even after adjusting for other prognostic factors. Increased CD4 T-cell activation may influence the more rapid immunological decline associated with X4 virus.

This study characterized the prevalence and patterns of antiretroviral-drug-resistance mutations according to plasma human immunodeficiency virus type 1 (HIV-1) RNA load in a large population of patients with HIV-1 infection who underwent testing for resistance mutations in routine clinical practice. HIV-1 genotypic resistance test results with linked clinical data were obtained from national resistance and clinical databases in the United Kingdom. Among 7861 tests, detection of > or =1 resistance mutation was most frequent at viral loads of 300-10,000 copies/mL and decreased statistically significantly at viral loads of >10,000 copies/mL. Major resistance mutations were commonly detected in the subset of tests that were performed among patients with viral loads of <1000 copies/mL (1001 [12.7%] of 7861 tests). We conclude that HIV-1 genotypic resistance testing is informative for patients with low viral loads.

Background: Nucleoside-sparing combination antiretroviral therapy (cART) regimens might be an attractive therapeutic option for HIV type-1 (HIV-1)-infected patients; however, the pharmacokinetic profiles of such regimens are frequently unknown., Methods: Fourteen HIV-1-infected patients (age 21-55 years, 64% male) on stable cART with plasma HIV RNA <50 copies/ml entered this Phase I pharmacokinetic study. In period 1, patients received tenofovir/emtricitabine/-darunavir/ritonavir (300/200/800/100 mg) all once daily. During period 2, raltegravir 400 mg twice daily was added to the regimen and in period 3 tenofovir/emtricitabine was discontinued. At steady state, intensive pharmacokinetic sampling was undertaken. Differences in the geometric mean ratio (GMR) for pharmacokinetic parameters between periods 2 versus 1 and period 3 versus 1 were assessed for darunavir and ritonavir (period 3 versus 2 for raltegravir)., Results: No statistically significant differences in pharmacokinetic parameters were observed between period 2 versus period 1. During period 3, darunavir GMR (95% confidence interval) values for trough and maximum plasma concentration (C(trough) and C(max)), area under the plasma concentration-time curve (AUC) and elimination half-life (t(1/2)) were 0.64 ng/ml (0.44-0.93), 1.05 ng/ml (0.90-1.24), 0.92 ng h/ml (0.78-1.08) and 0.69 h (0.46-1.05), respectively, when compared with period 1. No statistically significant changes were observed in ritonavir or raltegravir pharmacokinetic parameters. Darunavir C(trough)<550 ng/ml (the minimum effective concentration for protease-resistant HIV viral isolates) was observed in four patients during period 3 only. No clinically significant safety concerns were reported., Conclusions: Darunavir C(trough) is reduced by 36% when administered without tenofovir/emtricitabine in HIV-1-infected patients. This interaction might be of clinical significance in the management of individuals with protease-resistant HIV viral isolates.

Objective: To describe the clinical epidemiology of HIV-associated end-stage renal failure (HIV/ESRF) from 1998 to 2007 in the United Kingdom., Design: Observational cohort study., Setting: Seven leading HIV centres and affiliated renal clinics in the United Kingdom., Participants: A total of 21 951 patients in whom renal function was measured., Main Outcome Measure: Development of end-stage renal failure (ESRF) as defined by initiation of permanent renal replacement therapy (pRRT)., Results: Sixty-eight (0.31%) patients had HIV/ESRF, 44 (64.7%) of whom were black. The prevalence of ESRF in black patients increased over time from 0.26% in 1998-1999 to 0.92% in 2006-2007 (P for trend = 0.001). Overall 5-year survival from starting pRRT was 70.3%, and significantly better for black patients compared to those of other ethnicities (85.2 vs. 43.4%, P = 0.001). In multivariable analysis, black ethnicity was associated with a higher risk of ESRF [HR 6.93, 95% confidence interval (CI) 3.56, 13.48], whereas a higher current CD4 cell count was associated with reduced risk (HR: 0.83, 95% CI 0.76, 0.95) per 50 cells higher). No association was seen between current viral load or current highly active antiretroviral therapy (HAART) status and ESRF. On the basis of these observations, we estimate that 231 HIV-infected patients required pRRT in the United Kingdom in 2007, and an HIV prevalence of 0.51% among the United Kingdom pRRT recipients in that year., Conclusion: The prevalence of HIV/ESRF increased during the HAART era to reach nearly 1% in black patients, in whom favourable survival rates were observed. Earlier HIV diagnosis will be an important strategy to stem the rising trend of HIV/ESRF.

Introduction: Two recent studies have highlighted low rates of virological response to once daily nevirapine containing combination antiretroviral therapy (CART) in treatment naïve HIV-1 infected subjects., Aim: We assessed factors associated with treatment responses in a cohort of HIV-1 infected, therapy naïve individuals, commencing nevirapine CART with two nucleoside reverse transcriptase inhibitors (NRTI) containing either lamivudine or emtricitabine., Results: Between January 2002 and 2006, 173 subjects (80 female) met the study inclusion criteria. All subjects initially commenced on twice daily nevirapine with six different NRTI backbones. Mean follow up was 802 days. 49 (28%) subjects switched to once daily nevirapine, 23 (13%) within the first year. After 48 weeks of therapy, HIV RNA was < 50 copies/mL in 154/173 subjects (89%). A trend was observed towards improved virological outcome (HIV RNA < 50 copies/mL) and switching to once daily nevirapine during the first year of therapy (p=0.051)., Conclusion: Whilst awaiting the results of prospective studies assessing once daily nevirapine, our data describe high treatment success rates and good safety responses when switching to once daily nevirapine.

Abacavir is metabolized primarily by two enzymes: alcohol dehydrogenase and gluconyl transferase. Under normal conditions, alcohol is hepatically cleared via alcohol dehydrogenase to acetaldehyde, and subsequently by acetaldehyde dehydrogenase (ACD) to acetic acid. Disulfiram acts as an ACD blocker. Abacavir may also act as an inhibitor of alcohol dehydrogenase, which raises the possibility of disulfiram-like reactions (if complete inhibition occurs) or reduced alcohol tolerance (if partial inhibition occurs) occurring with abacavir therapy.

The worrying finding that up to 19% of newly diagnosed HIV-1 cases in the UK have genotypic evidence of transmitted drug-resistant HIV-1 (TrDR-HIV-1) does not concur with levels observed in one London centre. A study of the prevalence of resistance in primary HIV infection and newly diagnosed antiretroviral-naive individuals demonstrated significantly lower levels of TrDR-HIV-1 than previously reported. Variations in the prevalence of TrDR-HIV-1 may reflect the heterogeneity of methodologies and definitions used for resistance.

Our objective was to determine the relationship between highly active antiretroviral therapy (HAART), serum total oestradiol and sexual dysfunction in HIV-infected men. Sexual difficulties were recorded prospectively in a cohort of HIV-negative (or unknown status) gay/bisexual men (MSM) and a cohort of HIV-infected men. The HIV-infected men were divided into those on and not on HAART and by sexuality. Serum total oestradiol and testosterone levels were evaluated where possible. One hundred HIV-negative MSM and 73 HIV-infected men (88% MSM) were analysed. Low libido and erectile dysfunction (ED) were reported in the control group in 2% and 10% respectively. This compared to a prevalence of 26% for both problems in HIV-infected MSM not taking HAART. In those MSM on HAART reduced libido was noted in 48% and ED in 25%. In the group of men taking HAART the mean oestradiol level was 228 pmol/L and was significantly above normal limits. Low libido and ED are more commonly reported in HIV-infected men compared to gay men of negative or unknown status. HAART is associated with a higher prevalence of lack of sexual desire and raised serum oestradiol levels.

Post-exposure prophylaxis (PEP) is the standard of care for occupational exposure to HIV infection although it has not been evaluated following non-occupational exposure. Although the most effective methods for preventing HIV infection remain those that prevent exposure to HIV in the first place, this article discusses the dilemmas surrounding post-exposure therapy following non-occupational exposure.