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Summary Background The nonstructural 3 serine protease inhibitors ( PIs), boceprevir and telaprevir, represent the first in a new generation of directly acting antivirals against genotype 1 hepatitis C ( HCV) infection. When used in combination with pegylated interferon and ribavirin, these drugs greatly improve sustained virological response rates in both treatment-naïve patients and patients who have had previous virological failure on treatment. However, the addition of these new agents will increase the complexity of therapeutic regimens, the rates of side-effects and costs. Aims To review concisely the current evidence and to suggest current best practice, for the use of telaprevir and boceprevir in the management of chronic genotype 1 HCV infection. Methods These guidelines for the use of boceprevir and telaprevir have been formulated following extensive review of the current literature, are based on the consensus opinion of a panel of national experts, and have been openly discussed and debated at a national meeting of HCV care providers. Results We have made recommendations on a number of the key practical issues facing HCV care providers: (i) Which patients to treat?; (ii) Standards for the provision of care; (iii) Pre-treatment considerations; (iv) Which treatment regimens to use?; (v) Stopping rules; and (vi) Management of adverse effects. Finally, we have produced suggested algorithms for the assessment and treatment of these patients. Conclusions These UK Consensus guidelines indicate the current best practice for the use of boceprevir and telaprevir in the management of genotype 1 chronic HCV infection. [ABSTRACT FROM AUTHOR]

Objectives Current British HIV Association ( BHIVA) guidelines recommend that all patients with a CD4 count <350 cells/μ L are offered highly active antiretroviral therapy ( HAART). We identified risk factors for delayed initiation of HAART following a CD4 count <350 cells/μ L. Methods All adults under follow-up in 2008 who had a first confirmed CD4 count <350 cells/μ L from 2004 to 2008, who had not initiated treatment and who had >6 months of follow-up were included in the study. Characteristics at the time of the low CD4 cell count and over follow-up were compared to identify factors associated with delayed HAART uptake. Analyses used proportional hazards regression with fixed (sex/risk group, age, ethnicity, AIDS, baseline CD4 cell count and calendar year) and time-updated (frequency of CD4 cell count measurement, proportion of CD4 counts <350 cells/μ L, latest CD4 cell count, CD4 percentage and viral load) covariates. Results Of 4871 patients with a confirmed low CD4 cell count, 436 (8.9%) remained untreated. In multivariable analyses, those starting HAART were older [adjusted relative hazard ( aRH)/10 years 1.15], were more likely to be female heterosexual ( aRH 1.13), were more likely to have had AIDS ( aRH 1.14), had a greater number of CD4 measurements < 350 cells/μ L ( aRH/additional count 1.18), had a lower CD4 count over follow-up ( aRH/50 cells/μ L higher 0.57), had a lower CD4 percentage ( aRH/5% higher 0.90) and had a higher viral load ( aRH/log10 HIV-1 RNA copies/ml higher 1.06). Injecting drug users ( aRH 0.53), women infected with HIV via nonsexual or injecting drug use routes ( aRH 0.75) and those of unknown ethnicity ( aRH 0.69) were less likely to commence HAART. Conclusion A substantial minority of patients with a CD4 count < 350 cells/μ L remain untreated despite its indication. [ABSTRACT FROM AUTHOR]

Objective 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. Methods 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. Results The proportion of patients on ART with a viral load <50 HIV-1 RNA copies/mL increased from 62% in 2000 to 84% in 2007, and the proportion of all patients with a CD4 count <200 cells/μL 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 load >50 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 loads >50 copies/mL. Numbers of deaths are projected to remain low. Conclusions 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 loads >50 copies/mL is not projected to increase up to 2012. New drugs may be needed in future to sustain these positive trends. [ABSTRACT FROM AUTHOR]

We examined the prevalence of hepatitis C virus (HCV) infection among HIV-positive individuals in the UK, trends in HCV testing and the impact of HCV on HIV treatment outcomes. Trends over time in HCV prevalence were calculated using each patient’s most recent HCV status at the end of each calendar year. Logistic regression was used to identify factors associated with having a HCV antibody test, and Cox regression was used to determine whether HCV status was associated with the time to experiencing an immunological response to highly active antiretroviral treatment (HAART), time to virological response and viral rebound. Of the 31 765 HIV-positive individuals seen for care between January 1996 and September 2007, 20 365 (64.1%) individuals were tested for HCV, and 1807 (8.9%) had detectable HCV antibody. The proportion of patients in follow-up ever tested for HCV increased over time, from 782/8505 (9.2%) in 1996 to 14 280/17 872 (79.9%) in 2007. Nine thousand six hundred and sixty-nine individuals started HAART for the first time in or after January 2000, of whom, 396 (4.1%) were HCV positive. Presence of HCV infection did not affect initial virological response, virological rebound or immunological response. The cumulative prevalence of HCV in the UK CHIC Study is 8.9%. Despite UK guidelines, over 20% of HIV-positive individuals have not had their HCV status determined by 2007. HCV infection had no impact on HIV virological outcomes or immunological response to HIV treatment. The long-term impact on morbidity and mortality remain to be determined. [ABSTRACT FROM AUTHOR]

Background We describe the patterns of antiretroviral drug use at treatment initiation from 1996 to 2005 in a large UK multicentre cohort. Methods We examined trends over time and across 10 clinical sites in stage of disease and type of antiretroviral therapy (ART). Multivariable regression was used to identify factors associated with the CD4 cell count at ART initiation, and with the choice of a protease inhibitor (PI) over a nonnucleoside reverse transcriptase inhibitor (NNRTI), and use of nevirapine over efavirenz. Results A total of 14 252 patients initiated ART, of whom 54% had a CD4 count <200 cells/μL. The most important predictors of starting ART at a lower CD4 cell count were being male, nonwhite, and heterosexual or an injecting drug user ( P<0.0001). Among those starting ART, the use of highly active ART increased from 23% in 1996 to >96% from 2000 onwards. There were differences over time and across the clinics in the use of PIs vs. NNRTIs, in the choice of specific PIs, NNRTIs and nucleoside reverse transcriptase inhibitor (NRTI) backbone, and in the rate at which prescribing practices changed. Conclusions Clinic site and calendar year were important determinants of choice of drug at ART initiation, whereas clinical and demographic characteristics were more important in influencing the CD4 cell count at initiation of ART. [ABSTRACT FROM AUTHOR]

Background: Direct-acting anti-viral therapy (DAA) has transformed hepatitis C virus (HCV) care, particularly in patients with decompensated cirrhosis. However, their impact on hepatocellular carcinoma (HCC) remains unclear., Aim: To use a national registry of patients with advanced liver disease to explore the relationship between DAA therapy and HCC., Methods: All patients with de novo HCC post DAA therapy were frequency matched with patients who did not develop HCC. Demographic, clinical and laboratory data were obtained. Cross-sectional imaging and multidisciplinary team reports were reviewed for dates of HCC diagnosis and HCC progression. Patients were categorised by treatment outcome and time of HCC development. Data were examined by multivariable analysis and Kaplan-Meier estimation., Results: Eighty patients with HCC were compared with 165 patients without HCC, treated between June 2014 and September 2015. Mean follow-up from start of DAA therapy was 32.4 months. Twenty-eight patients were diagnosed with early HCC (within 6 months of therapy) and 52 presented late. Baseline nonmalignant lesions (HR: 1.99), thrombocytopaenia (HR: 1.59) and diabetes (HR: 1.68) increased likelihood of HCC. Response to therapy was reduced in patients who developed liver cancer (SVR in patients with HCC = 54/80 (68%), SVR in patients without HCC = 143/165 (87%), P < 0.001, OR: 3.13, 95% CI: 1.64-5.99). We found no difference between tumour size, progression or survival between viraemic and nonviraemic patients., Conclusion: There is no alteration in prognosis or cancer progression following HCC development after HCV treatment. However, baseline nonmalignant liver lesions, diabetes and thrombocytopaenia increase the risk of HCC, and HCC is associated with a decreased SVR rate., (© 2019 John Wiley & Sons Ltd.)

Background: The protease inhibitors lopinavir and atazanavir are both recommended for treatment of HIV-infected patients. Considerable inter-individual variability in plasma concentration has been observed for both drugs. The aim of this study was to evaluate which demographic factors and concomitant drugs are associated with lopinavir and atazanavir plasma concentration., Methods: Data from the Liverpool TDM (therapeutic drug monitoring) Registry were linked with the UK Collaborative HIV Cohort (CHIC) study. For each patient, the first measurement of lopinavir (twice daily) or atazanavir [once daily, ritonavir boosted (/r) or unboosted] plasma concentration was included. Linear regression was used to evaluate the association of dose, gender, age, weight, ethnicity and concomitant antiretroviral drugs or rifabutin with log-transformed drug concentration, adjusted for time since last intake., Results: Data from 439 patients on lopinavir (69% 400 mg/r, 31% 533 mg/r; 3% concomitant rifabutin) and 313 on atazanavir (60% 300 mg/r, 32% 400 mg/r, 8% 400 mg) were included. Multivariable models revealed the following predictors for lopinavir concentration: weight (11% decrease per additional 10 kg; P = 0.001); dose (25% increase for 533 mg/r; P = 0.024); and rifabutin (116% increase; P < 0.001). For atazanavir the predictors were dose (compared with 300 mg/r: 40% increase for 400 mg/r, 67% decrease for 400 mg; overall P < 0.001) and efavirenz (32% decrease; P = 0.016) but not tenofovir (P = 0.54)., Conclusions: This analysis confirms that efavirenz decreases atazanavir concentrations, and there was a negative association of weight and lopinavir concentrations. The strong impact of rifabutin on lopinavir concentration should be studied further.