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OBJECTIVES This observational study in antiretroviral treatment-experienced, HIV-1-infected adults explored the efficacy of etravirine plus darunavir/ritonavir (DRV group; n = 999) vs. etravirine plus an alternative boosted protease inhibitor (other PI group; n = 116) using pooled European cohort data. METHODS Two international (EuroSIDA; EUResist Network) and five national (France, Italy, Spain, Switzerland and UK) cohorts provided data (collected in 2007-2012). Stratum-adjusted (for confounding factors) Mantel-Haenszel differences in virological responses (viral load < 50 HIV-1 RNA copies/mL) and odds ratios (ORs) with 95% confidence intervals (CIs) were derived. RESULTS Baseline characteristics were balanced between groups except for previous use of antiretrovirals (≥ 10: 63% in the DRV group vs. 49% in the other PI group), including previous use of at least three PIs (64% vs. 53%, respectively) and mean number of PI resistance mutations (2.3 vs. 1.9, respectively). Week 24 responses were 73% vs. 75% (observed) and 49% vs. 43% (missing = failure), respectively. Week 48 responses were 75% vs. 73% and 32% vs. 30%, respectively. All 95% CIs around unadjusted and adjusted differences encompassed 0 (difference in responses) or 1 (ORs). While ORs by cohort indicated heterogeneity in response, for pooled data the difference between unadjusted and adjusted for cohort ORs was small. CONCLUSIONS These data do not indicate a difference in response between the DRV and other PI groups, although caution should be applied given the small size of the other PI group and the lack of randomization. This suggests that the efficacy and virology results from DUET can be extrapolated to a regimen of etravirine with a boosted PI other than darunavir/ritonavir.

Objectives The aim of the study was to identify possible causes of pancreatic insufficiency in patients with HIV infection. Methods A retrospective analysis of 233 HIV-positive patients for whom faecal elastase measurement was available was performed to investigate potential associations with core demographic data, HIV infection characteristics, degree of immunosuppresion, exposure to antiretroviral therapy (ART), alcohol misuse, diabetes, hepatitis C virus (HCV) infection, triglyceride and cholesterol levels and symptomatology. The response to pancreatic enzyme replacement for patients with evidence of insufficiency was also evaluated. Results Of 233 patients, 104 (45%) had evidence of pancreatic exocrine insufficiency (faecal elastase

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.

Background In the MONotherapy in Europe with Tmc114 (MONET) trial, darunavir/ritonavir (DRV/r) monotherapy showed noninferior efficacy vs. two nucleoside reverse transcriptase inhibitors (NRTIs) plus DRV/r at the primary 48-week analysis. The trial was continued to week 144 to assess the durability of the results. Methods A total of 256 patients with viral load

Objective The aim of the study was to compare the metabolic and morphological effects of enfuvirtide plus an optimized background (OB) regimen vs. OB alone (control group) in treatment-experienced patients in the T-20 vs. Optimized Regimen Only (TORO) studies. Methods Body composition and metabolic changes were investigated in patients over 48 weeks, based on fasting chemistries, body weight, and other anthropometric measurements. Dual-energy X-ray absorptiometry (DEXA) and computed tomography (CT) scans were performed in a patient subgroup (n=155) at baseline and at weeks 24 and 48. Results At week 48, mean changes from baseline were similar between treatment groups for glucose, insulin, C-peptide, total cholesterol, low-density lipoprotein (LDL) cholesterol, very low density lipoprotein (VLDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglyceride levels. The enfuvirtide group experienced a significant increase in body weight [mean change from baseline +0.99 kg; 95% confidence interval (CI) +0.54, +1.44] and, in those who had body scans, there was a significant increase in truncal fat (by DEXA: median change +419.4 g; 95% CI+71.3, +767.5) and total fat [visceral adipose tissue (VAT)+subcutaneous adipose tissue (SAT) by single-slice abdominal CT scan: median change +25.5 cm2; 95% CI+8.9, +42.0] over 48 weeks; significant increases in these parameters were not seen in the control group. There was no significant change in truncal:peripheral fat ratio in either the enfuvirtide or the control group. Conclusion The addition of enfuvirtide to an OB regimen does not appear to have unfavourable effects on fat distribution or metabolic parameters.

OBJECTIVES Involvement of people living with HIV (PLHIV) in the design of HIV cure studies is important, given the potential risks to participants. We present results of an international survey of PLHIV to define these issues and inform cure research. METHODS PLHIV were recruited in June-November 2014 through HIV websites, advocacy forums, social media and 12 UK HIV clinics. The survey included questions concerning demographics, HIV disease history, the desirability of types of cure and the patient's willingness to accept potential toxicity and treatment interruption (TI). We examined factors associated with TI and willingness to accept substantial risks. RESULTS A total of 982 PLHIV completed the survey; 87% were male, 79% white and 81% men who have sex with men (MSM). Fifty-one per cent were aged 25-44 years and 69% were UK residents. The median time since diagnosis was 7 years [interquartile range (IQR) 2-17 years]. Eighty-eight per cent were receiving antiretrovirals (91% reported undetectable viral load). Health/wellbeing improvements (96%) and an inability to transmit HIV (90%) were more desirable cure characteristics than testing HIV-negative (69%). Ninety-five per cent were interested in participating in cure studies, and 59% were willing to accept substantial risks. PLHIV with a low CD4 count [201-350 cells/μL vs. ≥ 350 cells/μL; odds ratio (OR) 2.11; 95% confidence interval (CI) 1.11-4.00] were more likely to accept risks, whereas those with limited knowledge of HIV treatments vs. excellent/good knowledge and those aged ≥ 65 years vs. 45-64 years were less likely to accept risks [OR 0.58 (95% CI 0.37-0.90) and OR 0.18 (95% CI 0.07-0.45), respectively]. TI was acceptable for 62% of participants, with the main concerns being becoming unwell (82%), becoming infectious (76%) and HIV spreading through the body (76%). CONCLUSIONS Cure research was highly acceptable to the PLHIV surveyed. Most individuals would accept risks, including TI, even in the absence of personal benefit. An optimal cure would improve health and minimize onward transmission risk.

J Wang, A Ozzard, M Nathan, M Atkins, M Nelson, B Gazzard and M BowerDepartment of Oncology and HIV Medicine, Chelsea and Westminster Hospital, London, UKIntroductionEpstein–Barr virus (EBV) is detected in the cerebrospinal fluid (CSF) in people with HIV infectionwho develop primary cerebral lymphoma (PCL). However, EBV may also be detected in the CSF ofpatients without PCL, and here the significance is uncertain.MethodsNinety-eight HIV-positive patients had lumbar punctures performed and polymerase chain reaction(PCR) for EBV was undertaken on the CSF. Thirty-eight patients had non-Hodgkin’s lymphoma(NHL), including four with PCL. Sixty patients had a CSF examination for other indications. Theclinicopathological details, symptoms, diagnosis, CSF and neuroimaging findings and therapy attime of CSF were recorded and correlated with CSF EBV PCR results.ResultsEBV was detected in the CSF in three of four patients (75%) with PCL, one of three (33%) withsystemic lymphoma and meningeal involvement, and four of 31 (13%) with systemic lymphoma andno meningeal disease. Seven of 60 patients (12%) without lymphoma were CSF EBV-positive. Therewere no differences in immunological, clinical, biochemical or radiological parameters betweenpatients with and without EBV in the CSF. After a median follow-up time of 30 weeks (maximum102 weeks), none of the seven CSF EBV-positive patients has developed PCL.ConclusionEBV was detected in up to 12% of patients with neurological symptoms but without lymphoma.A positive result did not correlate with more advanced immunosuppression or a particularneurological diagnosis. Patients with EBV in their CSF did not appear to be at increased risk ofdeveloping PCL in the short term.Keywords: cerebrospinal fluid, Epstein–Barr virus, HIV, primary cerebral lymphomaReceived: 11 October 2006, accepted 6 March 2007

Background The use of highly active antiretroviral therapy (HAART) has profoundly altered the life expectancy of individuals infected with HIV. Metabolic abnormalities associated with antiretrovirals and cumulative exposure to combination antiretroviral therapy, including dyslipidaemia and insulin resistance, have been linked to an increased risk of myocardial infarction. Methods Longitudinal data from a large prospectively collected clinical database were analysed. All patients who commenced first antiretroviral therapy (ART) [two nucleoside reverse transcriptase inhibitors (NRTIs)+one nonnucleoside reverse transcriptase inhibitor (NNRTI) or one active protease inhibitor (PI)] since 1996 were identified. Patients with elevated cholesterol levels [>5.5 mmol/L (215 mg/dL)] prior to therapy initiation were excluded. Quantitative data were categorized into quartiles and presented stratified by individuals developing abnormal levels of cholesterol during first-line HAART. Event time was defined as time from commencing first-line ART to either development of cholesterol level >6.5 mmol/L (254 mg/dL) or switch of first-line therapy. The Kaplan–Meier product limit survival method was used to estimate time to abnormal cholesterol level, and the χ2 test was used for comparisons between drug classes. Cox's proportional hazards regression analysis was used to identify factors predicting a likelihood of raised cholesterol level. Results A total of 1664 patients were included in the study: 57.1% on two NRTIs+one NNRTI, 38.4% on two NRTIs+one PI, and 4.4% on two NRTIs+a boosted PI regimen. Regimens containing stavudine or PIs were associated with a significantly higher event risk and earlier time to event. No differences between efavirenz and nevirapine or between didanosine and lamivudine were observed. In 28 patients exposed to the combination of tenofovir+lamivudine+efavirenz, there were no episodes of elevated cholesterol level. Conclusion Dyslipidaemia has emerged as an important issue in HIV-infected individuals receiving antiretroviral therapy. This study demonstrates that age at start of therapy, baseline cholesterol level, stavudine use and PI use are all associated with increased risk of hypercholesterolemia on initial therapy. Both NRTI and NNRTI/PI choice influence risk of hypercholesterolaemia.

Objectives Highly active antiretroviral therapy (HAART) has been advocated for the management of primary HIV-1 infection. We investigated the use of a nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen in this setting. Methods Twenty-one antiretroviral-naive individuals with early HIV-1 disease were treated with a combination of efavirenz and Combivir (GlaxoSmithKline, Uxbridge, Middlesex, UK). They were evaluated for immune and lymphocyte function by standard immunological assays. Results The median time to an undetectable HIV-1 viral load was 12 weeks (range 4–36 weeks). CD4 and CD16/56 counts increased during treatment and CD8 counts decreased minimally. The main side-effects observed were transient sleep disturbances (five patients). In addition, we observed a decrease in lymphocyte activation as assessed by CD38 surface expression. Conclusions This study demonstrates that primary HIV-1 infection can be treated with NNRTI-based HAART.

Objective Since the introduction of highly active antiretroviral therapy (HAART) there has been a dramatic reduction in the incidence of Kaposi sarcoma (KS) and an improvement in survival. We wished to examine whether the outcome in pulmonary KS (pKS) has also altered. Methods In a single-institution cohort of 1140 HIV-positive patients with KS, 305 patients were diagnosed in the HAART era (1996–2004). We examined the clinicopathological features and outcomes of these patients, of whom 25 had pKS and 280 did not. Results Patients with pKS had lower CD4 cell counts at the time of KS diagnosis (Mann–Whitney U-test P=0.005). The incidence of pKS was higher in African patients than in non-African patients in this sample (Fisher's test, P=0.001). There were no significant differences in age, gender, plasma HIV-1 viral load or prior HAART treatment at the time of KS diagnosis. Five-year overall survival in the pKS group was 49% [95% confidence interval (CI) 26–73%] as compared with 82% (95% CI 76–87%) for the non-pKS group (log rank, P

Effective antiretroviral therapy (ART) has transformed the care of people with HIV, but it is important to monitor time trends in indicators of treatment success and antic future changes.We assessed time trends from 2000 to 2007 in several indicators of treatment success in the UK Collaborative HIV Cohort (CHIC) Study, and using national HIV data from the Health Protection Agency (HPA) we developed a model to project future trends.The proportion of patients on ART with a viral load50 HIV-1 RNA copies/mL increased from 62% in 2000 to 84% in 2007, and the proportion of all patients with a CD4 count200 cells/microL decreased from 21% to 10%. During this period, the number of patients who experienced extensive triple class failure (ETCF) rose from 147 (0.9%) to 1771 (3.9%). The number who experienced such ETCF and had a current viral load50 copies/mL rose fromz 118 (0.7%) to 857 (1.9%). Projections to 2012 suggest sustained high levels of success, with a continued increase in the number of patients who have failed multiple drugs but a relatively stable number of such patients experiencing viral loads50 copies/mL. Numbers of deaths are projected to remain low.There have been continued improvements in key indicators of success in patients with HIV from 2000 to 2007. Although the number of patients who have ETCF is projected to rise in the future, the number of such patients with viral loads50 copies/mL is not projected to increase up to 2012. New drugs may be needed in future to sustain these positive trends.

(1) All HIV-positive patients should have serum markers for hepatitis B checked (HBsAg, anti-HBc and/or antiHBs) tests within a month of diagnosis [II]. (2) All those negative for hepatitis B markers should be immunized and anti-HBs checked at 12 weeks. Patients failing to respond to a conventional course of 20 mg vaccine should received booster doses and/or a repeat vaccination cycle with the 40 mg dose. Response to vaccine may be reduced if the CD4 count is less than 500 cells/mm [I]. (3) Those patients with a CD4 counto200 cells/mm not on ART should receive combination therapy first and with immune recovery, subsequent immunization. (4) Following successful immunization, anti-HB levels should be checked yearly and booster doses of vaccine should be given to those with an anti-HB levelo100 im/ L [IV]. (5) Persons who fail to seroconvert to HBV vaccine and are at continuing risk of HBV infection should have annual HBV markers performed (HBsAg and anti-HBc) [IV]. (6) All patients who are anti-HBc positive but HBsAg negative are at risk of HBV reactivation. HBV markers including HBV-DNA should be rechecked annually or if the liver function tests (AST/ALT) become abnormal [II]. (7) All HIV-infected persons should have serum markers for HBV checked before antiretroviral (ARV) therapy is commenced and then reassessed at least once a year. Decisions on appropriate ART combinations can then be made [IV].