Objectives Darunavir was designed for activity against HIV resistant to other protease inhibitors (PIs). We assessed the efficacy, tolerability and risk factors for virological failure of darunavir for treatment-experienced patients seen in clinical practice. Methods We included all patients in the Swiss HIV Cohort Study starting darunavir after recording a viral load above 1000 HIV-1 RNA copies/mL given prior exposure to both PIs and nonnucleoside reverse transcriptase inhibitors. We followed these patients for up to 72 weeks, assessed virological failure using different loss of virological response algorithms and evaluated risk factors for virological failure using a Bayesian method to fit discrete Cox proportional hazard models. Results Among 130 treatment-experienced patients starting darunavir, the median age was 47 years, the median duration of HIV infection was 16 years, and 82% received mono or dual antiretroviral therapy before starting highly active antiretroviral therapy. During a median patient follow-up period of 45 weeks, 17% of patients stopped taking darunavir after a median exposure of 20 weeks. In patients followed beyond 48 weeks, the rate of virological failure at 48 weeks was at most 20%. Virological failure was more likely where patients had previously failed on both amprenavir and saquinavir and as the number of previously failed PI regimens increased. Conclusions As a component of therapy for treatment-experienced patients, darunavir can achieve a similar efficacy and tolerability in clinical practice to that seen in clinical trials. Clinicians should consider whether a patient has failed on both amprenavir and saquinavir and the number of failed PI regimens before prescribing darunavir.

Objectives The aim of the study was to establish a methodology for evaluating the hepatitis C continuum of care in HIV/hepatitis C virus (HCV)‐coinfected individuals and to characterize the continuum in Europe on 1 January 2015, prior to widespread access to direct‐acting antiviral (DAA) therapy. Methods Stages included in the continuum were as follows: anti‐HCV antibody positive, HCV RNA tested, currently HCV RNA positive, ever HCV RNA positive, ever received HCV treatment, completed HCV treatment, follow‐up HCV RNA test, and cure. Sustained virological response (SVR) could only be assessed for those with a follow‐up HCV RNA test and was defined as a negative HCV RNA result measured > 12 or 24 weeks after stopping treatment. Results Numbers and percentages for the stages of the HCV continuum of care were as follows: anti‐HCV positive (n = 5173), HCV RNA tested (4207 of 5173; 81.3%), currently HCV RNA positive (3179 of 5173; 61.5%), ever HCV RNA positive (n = 3876), initiated HCV treatment (1693 of 3876; 43.7%), completed HCV treatment (1598 of 3876; 41.2%), follow‐up HCV RNA test to allow SVR assessment (1195 of 3876; 30.8%), and cure (629 of 3876; 16.2%). The proportion that achieved SVR was 52.6% (629 of 1195). There were significant differences between regions at each stage of the continuum (P < 0.0001). Conclusions In the proposed HCV continuum of care for HIV/HCV‐coinfected individuals, we found major gaps at all stages, with almost 20% of anti‐HCV‐positive individuals having no documented HCV RNA test and a low proportion achieving SVR, in the pre‐DAA era.

Background In human immunodeficiency virus (HIV)–positive adults, low CD4 cell counts despite fully suppressed HIV-1 RNA on antiretroviral therapy (ART) have been associated with increased risk of morbidity and mortality. We assessed the prevalence and outcomes of poor immune response (PIR) in children receiving suppressive ART. Methods Sixteen cohorts from the European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) contributed data. Children <18 years at ART initiation, with sustained viral suppression (VS) (≤400 copies/mL) for ≥1 year were included. The prevalence of PIR (defined as World Health Organization advanced/severe immunosuppression for age) at 1 year of VS was described. Factors associated with PIR were assessed using logistic regression. Rates of acquired immunodeficiency syndrome (AIDS) or death on suppressive ART were calculated by PIR status. Results Of 2318 children included, median age was 6.4 years and 68% had advanced/severe immunosuppression at ART initiation. At 1 year of VS, 12% had PIR. In multivariable analysis, PIR was associated with older age and worse immunological stage at ART start, hepatitis B coinfection, and residing in Thailand (all P ≤ .03). Rates of AIDS/death (95% confidence interval) per 100 000 person-years were 1052 (547, 2022) among PIR versus 261 (166, 409) among immune responders; rate ratio of 4.04 (1.83, 8.92; P < .001). Conclusions One in eight children in our cohort experienced PIR despite sustained VS. While the overall rate of AIDS/death was low, children with PIR had a 4-fold increase in risk of event as compared with immune responders.

Objectives: To assess the effect of migrant status on treatment outcomes among children living with HIV in Europe.Methods: Children aged < 18 years at the start of antiretroviral therapy (ART) in European paediatric HIV observational cohorts where ≥ 5% of children were migrants (defined as born abroad) were included. Three outcomes were considered: (i) severe immunosuppression-for-age; (ii) viraemic viral load (≥ 400 copies/ mL) at 1 year after ART initiation; and (iii) AIDS/death after ART initiation. The effect of migrant status was assessed using univariable and multivariable logistic and Cox models.Results: Of 2620 children included across 12 European countries, 56% were migrants. At ART initiation, migrant children were older than domestic-born children (median 6.1 vs. 0.9 years, p < 0.001), with slightly higher proportions being severely immunocompromised (35% vs. 33%) and with active tuberculosis (2% vs. 1%), but a lower proportion with an AIDS diagnosis (14% vs. 19%) (all p < 0.001). At 1 year after beginning ART, a lower proportion of migrant children were viraemic (18% vs. 24%) but there was no difference in multivariable analysis (p = 0.702), and no difference in severe immunosuppression (p = 0.409).However, there was a trend towards higher risk of AIDS/death in migrant children (adjusted hazard ratio = 1.51, 95% confidence interval: 0.96-2.38, p = 0.072). Conclusions:After adjusting for characteristics at ART initiation, migrant children have virological and immunological outcomes at 1 year of ART that are comparable to those who are domestic-born, possibly indicating equity in access to healthcare in Europe. However, there was some evidence of a difference in AIDS-free survival, which warrants further monitoring.

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