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Introduction: Clinically evaluating genotypic interpretation systems is essential to provide optimal guidance in designing potent individualized HIV-regimens. This study aimed at investigating the ability of the latest Rega algorithm to predict virological response on a short and longer period. Materials & Methods: 9231 treatment changes episodes were extracted from an integrated patient database. The virological response after 8, 24 and 48 weeks was dichotomized to success and failure. Success was defined as a viral load below 50 copies/ml or alternatively, a 2 log decrease from the baseline viral load at 8 weeks. The predictive ability of Rega version 8 was analysed in comparison with that of previous evaluated version Rega 5 and two other algorithms (ANRS v2011.05 and Stanford HIVdb v6.0.11). A logistic model based on the genotypic susceptibility score was used to predict virological response, and additionally, confounding factors were added to the model. Performance of the models was compared using the area under the ROC curve (AUC) and a Wilcoxon signed-rank test. Results: Per unit increase of the GSS reported by Rega 8, the odds on having a successful therapy response on week 8 increased significantly by 81% (OR = 1.81, CI = [1.76–1.86]), on week 24 by 73% (OR = 1.73, CI = [1.69–1.78]) and on week 48 by 85% (OR = 1.85, CI = [1.80–1.91]). No significant differences in AUC were found between the performance of Rega 8 and Rega 5, ANRS v2011.05 and Stanford HIVdb v6.0.11, however Rega 8 had the highest sensitivity: 76.9%, 76.5% and 77.2% on 8, 24 and 48 weeks respectively. Inclusion of additional factors increased the performance significantly. Conclusion: Rega 8 is a significant predictor for virological response with a better sensitivity than previously, and with rules for recently approved drugs. Additional variables should be taken into account to ensure an effective regimen. [ABSTRACT FROM AUTHOR]

Background. Abacavir-lamivudine and tenofovir DF-emtricitabine fixed-dose combinations are commonly used as first-line antiretroviral therapies. However, few studies have comprehensively compared their relative safety profiles. Methods. In this European, multicenter, open-label, 96-week study, antiretroviral-naive adult subjects with human immunodeficiency virus (HIV) infection were randomized to receive either abacavir-lamivudine or tenofovir- emtricitabine with efavirenz. Primary analyses were conducted after 48 weeks of treatment. Bone mineral density (BMD), a powered secondary end point, was assessed by dual energy x-ray absorptiometry. Bone turnover markers (osteocalcin, procollagen 1 N-terminal propeptide, bone specific alkaline phosphatase, and type 1 collagen cross-linked C telopeptide [CTx]) were assessed in an exploratory analysis. Results. A total of 385 subjects were enrolled in the study. BMD loss was observed in both treatment groups, with a significant difference in the change from baseline in both total hip (abacavir-lamivudine group, -1.9%; tenofovir-emtricitabine group, -3.6%; P < .001) and lumbar spine (abacavir-lamivudine group, -1.6%; tenofoviremtricitabine group, -2.4%; P = .036). BMD loss of ⩾6% was more common in the tenofovir-emtricitabine group (13% of the tenofovir-emtricitabine group vs 3% of the abacavir-lamivudine group had a loss of ⩾6% in the hip; 15% vs 5% had a loss of ⩾6% in the spine). Bone turnover markers increased in both treatment groups over the first 24 weeks, stabilizing or decreasing thereafter. Increases in all markers were significantly greater in the tenofovir-emtricitabine treatment group than in the abacavir-lamivudine group at week 24. All but CTx remained significantly different at week 48 (eg, osteocalcin: abacavir-lamivudine group, +8.07 mg/L; tenofovir-emtricitabine group, +11.92 mg/L; P < .001). Conclusions. This study demonstrated the impact of first-line treatment regimens on bone. Greater increases in bone turnover and decreases in BMD were observed in subjects treated with tenofovir-emtricitabine than were observed in subjects treated with abacavir-lamivudine. [ABSTRACT FROM AUTHOR]

Nonadherence to antiretroviral therapy (ART) jeopardizes good clinical outcome in people living with HIV. In a single-center prospective study, prevalence and correlates of nonadherence were investigated in 43 patients on ART. Nonadherence was assessed using Medication Event Monitoring System® (MEMS®), self-report and collateral report of treating physicians. Based on MEMS® data, median taking adherence, dosing adherence, and timing adherence was 98% (interquartile range [IQR] = 5.3), 91.5% (IQR = 18), and 86% (IQR = 31.5), respectively. The median number of drug holidays per 100 days was 0.8 (IQR = 4.8). The prevalence of nonadherence measured by MEMS® was 40%. Self-reported nonadherence and collateral report of nonadherence by physicians varied from 5% to 41% and 24% to 28%, respectively. Patients were categorized as adherent or nonadherent based on a clinically validated algorithm derived from MEMS® parameters. Nonadherent patients used significantly more escaping coping strategies (p = 0.003) and planned problem solving strategies (p = 0.049), were prescribed significantly more antiretroviral medications (p = 0.02) and were significantly longer on ART (p = 0.04) than adherent patients. Identified correlates of nonadherence may help clinicians in detecting patients with HIV at risk for nonadherence and can support the development of adherence enhancing interventions. [ABSTRACT FROM AUTHOR]

We describe a 66-year-old woman with therapy-refractory cryoglobulinemia treated with rituximab, plasmapheresis, and steroids; a case of fatal meningoencephalitis caused by Acanthamoeba spp. then developed. Such infections are rare and show an unusually rapid course (possibly related to rituximab). [ABSTRACT FROM AUTHOR]

Introduction We studied factors associated with the continuum of HIV care in Belgium. Methods Data of the national registration of new HIV diagnosis and of the national cohort of HIV-infected patients in care were combined to obtain estimates of and factors related with proportions of HIV-infected patients in each step of the continuum of care from diagnosis to suppressed viral load (VL). Factors associated with ignorance of HIV seropositivity were analyzed among patients co-infected with HIV and STI in the Belgian STI sentinel surveillance network. Associated factors were identified by multivariate logistic regression. Results Among 4038 individuals diagnosed with HIV between 2007 and 2010, 90.3% were linked to care. Of 11684 patients in care in 2010, 90.8% were retained in care up to the following year, 88.3% of those were on ART, of whom 95.3% had suppressed VL (<500 cp/ml) (Figure 1). In multivariate analyses, factors associated with ignoring HIV+ status were being younger (p<0.001), being heterosexual compared to MSM, and of a region of origin other than Belgium, Sub-Saharan Africa and Europe. Non-Belgian regions of origin were associated with lower entry and retention in care (p<0.001 for both). Preoperative HIV testing was associated with lower entry in care (p=0.003). MSM had a higher retention in care (p<0.001), whilst IDU had lower retention (p=0.004). Low CD4 at first clinical contact and clinical reasons for HIV testing were independently associated with being on ART (p<0.001 for both); whilst prenatal HIV diagnosis was associated with lower proportion on ART (p=0.016) and lower proportion with suppressed VL among those on ART (p=0.005). Older age was associated with both being on ART and having suppressed VL among those on ART (p=0.007 and p<0.001 respectively), independently of time since HIV diagnosis (Table 1). Conclusions Regions of origin and risk groups (MSM/heterosexual/IDU) are the main factors associated with ignorance of HIV seropositivity, entry and retention in care, but once the HIV patient is retained in care, no effect of these factors on the proportions on ART and with suppressed VL are observed. The association of prenatal HIV diagnosis and proportions on ART and with suppressed VL could be biased by transitory CD4 disturbances during pregnancy and ART discontinuation after pregnancy. The higher probabilities of older patients to be on ART and have suppressed VL once retained in care could be influenced by factors not studied here like comorbidities, adherence or duration on ART. [ABSTRACT FROM AUTHOR]

Nonadherence to antiretroviral therapy (ART) jeopardizes good clinical outcome in people living with HIV. In a single-center prospective study, prevalence and correlates of nonadherence were investigated in 43 patients on ART. Nonadherence was assessed using Medication Event Monitoring System® (MEMS®), self-report and collateral report of treating physicians. Based on MEMS® data, median taking adherence, dosing adherence, and timing adherence was 98% (interquartile range [IQR] = 5.3), 91.5% (IQR = 18), and 86% (IQR = 31.5), respectively. The median number of drug holidays per 100 days was 0.8 (IQR = 4.8). The prevalence of nonadherence measured by MEMS® was 40%. Self-reported nonadherence and collateral report of nonadherence by physicians varied from 5% to 41% and 24% to 28%, respectively. Patients were categorized as adherent or nonadherent based on a clinically validated algorithm derived from MEMS® parameters. Nonadherent patients used significantly more escaping coping strategies (p = 0.003) and planned problem solving strategies (p = 0.049), were prescribed significantly more antiretroviral medications (p = 0.02) and were significantly longer on ART (p = 0.04) than adherent patients. Identified correlates of nonadherence may help clinicians in detecting patients with HIV at risk for nonadherence and can support the development of adherence enhancing interventions. [ABSTRACT FROM AUTHOR]

Recent studies suggest that intensive care unit patients treated with amikacin frequently do not attain the desired pharmacokinetic/pharmacodynamic (PK/PD) target, i.e. peak amikacin concentration ( C peak ) to minimum inhibitory concentration (MIC) ratio of ≥8, when a single dose of 15 mg/kg is used. No data are available for patients admitted to the emergency department (ED). The aim of this prospective randomised controlled study was to determine PK/PD target attainment in ED patients presenting with severe sepsis or septic shock treated with 15 mg/kg versus 25 mg/kg amikacin. Patients were randomly assigned to receive amikacin 25 mg/kg or 15 mg/kg. Amikacin C peak values were determined. The primary outcome was target attainment defined as C peak /MIC ≥ 8 both using EUCAST susceptibility breakpoints and actually documented MICs as denominator. A total of 104 patients were included. The EUCAST-based target was attained in 76% vs. 40% of patients assigned to the 25 mg/kg vs. 15 mg/kg dose groups ( P  <   0.0001). Target attainment using actual MICs (median of 2 mg/L, documented in 48 isolated Gram-negative pathogens) was achieved in 95% vs. 94% of patients in the 25 mg/kg vs. 15 mg/kg dose groups ( P  = 0.969). Risk factors associated with PK/PD target failure were identified in the multivariable analysis. At least 25 mg/kg amikacin as a single dose should be used in ED patients with severe sepsis and septic shock to attain the EUCAST-based PK/PD target. However, when using local epidemiology as denominator, 15 mg/kg appears to be sufficient. [ ClinicalTrials.gov ID: NCT02365272 . [ABSTRACT FROM AUTHOR]

Abstract: Background: Resistance testing has been implemented into clinical guidelines as it has shown some beneficial effect on subsequent therapy response. Case report: Routine population-based genotypic resistance testing for a newly diagnosed HIV-1 patient revealed the presence of resistance mutations M41L, V179D and T215E within reverse transcriptase and no mutations within protease. Four weeks after initiation of the combination tenofovir+lamivudine+efavirenz, no response was observed despite good adherence to therapy and efavirenz drug levels in the therapeutic range. Retrospective single genome sequencing of the baseline sample revealed the presence of minority viral variants with additional mutations: a mutation conferring resistance to lamivudine (M184IV), a thymidine associated mutation (K219R) and mutations possibly associated with non-nucleoside reverse transcriptase resistance (F227S, M230IV). Conclusions: This case illustrates that undetected drug-resistant minority variants can reduce the efficacy of a normally very potent first-line regimen tenofovir+lamivudine+efavirenz. The presence of drug-resistance mutations at diagnosis should be considered as a warning sign against the use of low genetic barrier drugs in first-line regimens, even when these drugs are considered to be active according to routine resistance testing. [Copyright &y& Elsevier]

Presents a letter to the editor about the impact of levels of drug resistance among therapy-naive HIV-infected patients on treatment response.