Epilepsia partialis continua complicated by disseminated tuberculosis and hemophagocytic lymphohistiocytosis: a case report.

BACKGROUND: We describe a patient copresenting with epilepsia partialis continua, tuberculosis, and hemophagocytic lymphohistiocytosis. To our knowledge, this is the first documented case of this triad. CASE PRESENTATION: A 54-year-old black South African woman presented to a hospital in Scotland with an acute history of right-sided facial twitching, breathlessness, and several months of episodic night sweats. Clinical examination revealed pyrexia and continuous, stereotyped, right-sided facial contractions. These worsened with speech and continued through sleep. A clinical diagnosis of epilepsia partialis continua was made, and we provide a video of her seizures. Computed tomographic imaging of the chest and serous fluid analyses were consistent with a diagnosis of disseminated Mycobacterium tuberculosis. An additional diagnosis of hemophagocytic lymphohistiocytosis was made following the identification of pancytopenia and hyperferritinemia in peripheral blood, with hemophagocytosis evident in bone marrow investigation. We provide images of her hematopathology. The patient was extremely unwell and was hospitalized for 6 months, including two admissions to the intensive care unit for ventilatory support. She was treated successfully with high doses of antiepileptic drugs (benzodiazepines, levetiracetam, and phenytoin) and 12 months of oral antituberculosis therapy, and she underwent chemotherapy with 8 weeks of etoposide and dexamethasone for hemophagocytic lymphohistiocytosis, followed by 12 months of cyclosporine and prednisolone. CONCLUSIONS: This combination of pathologies is unusual, and this case report helps educate clinicians on how such a patient may present and be managed. A lack of evidence surrounding the coexpression of this triad may represent absolute rarity, underdiagnosis, or incomplete case ascertainment due to early death caused by untreated tuberculosis or hemophagocytic lymphohistiocytosis. Further research is needed

Neurocognitive function in HIV infected patients on antiretroviral therapy

OBJECTIVE To describe factors associated with neurocognitive (NC) function in HIV-positive patients on stable combination antiretroviral therapy. DESIGN We undertook a cross-sectional analysis assessing NC data obtained at baseline in patients entering the Protease-Inhibitor-Monotherapy-Versus-Ongoing-Triple therapy (PIVOT) trial. MAIN OUTCOME MEASURE NC testing comprised of 5 domains. Raw results were z-transformed using standard and demographically adjusted normative datasets (ND). Global z-scores (NPZ-5) were derived from averaging the 5 domains and percentage of subjects with test scores >1 standard deviation (SD) below population means in at least two domains (abnormal Frascati score) calculated. Patient characteristics associated with NC results were assessed using multivariable linear regression. RESULTS Of the 587 patients in PIVOT, 557 had full NC results and were included. 77% were male, 68% Caucasian and 28% of Black ethnicity. Mean (SD) baseline and nadir CD4+ lymphocyte counts were 553(217) and 177(117) cells/µL, respectively, and HIV RNA was <50 copies/mL in all. Median (IQR) NPZ-5 score was -0.5 (-1.2/-0) overall, and -0.3 (-0.7/0.1) and -1.4 (-2/-0.8) in subjects of Caucasian and Black ethnicity, respectively. Abnormal Frascati scores using the standard-ND were observed in 51%, 38%, and 81%, respectively, of subjects overall, Caucasian and Black ethnicity (p<0.001), but in 62% and 69% of Caucasian and Black subjects using demographically adjusted-ND (p = 0.20). In the multivariate analysis, only Black ethnicity was associated with poorer NPZ-5 scores (P<0.001). CONCLUSIONS In this large group of HIV-infected subjects with viral load suppression, ethnicity but not HIV-disease factors is closely associated with NC results. The prevalence of abnormal results is highly dependent on control datasets utilised. TRIAL REGISTRY ClinicalTrials.gov, NCT01230580

Use of contraindicated antiretroviral drugs in people with HIV/HCV coinfections receiving HCV treatment with direct-acting antivirals-Results from the EuroSIDA study.

OBJECTIVES Our objective was to determine whether antiretroviral drugs (ARVs) were used according to the European AIDS Clinical Society (EACS) guidelines for people with HIV/hepatitis C virus (HCV) coinfection treated with direct-acting antivirals (DAAs) between 30 November 2014 and 31 December 2019 in the pan-European EuroSIDA study. METHODS At each publication date of the EACS guidelines, plus 3 and 6 months, we calculated the number of people receiving DAAs with potential and actual ARV contraindications ('red shading' in the EACS guidelines). We used logistic regression to investigate factors associated with using contraindicated ARVs. RESULTS Among 1406 people starting DAAs, the median age was 51 years, 75% were male, 57% reported injected drug use as an HIV risk, and 76% were from western Europe. Of 1624 treatment episodes, 609 (37.5%) occurred while the patient was receiving ARVs with potential contraindications; among them, 38 (6.2%; 95% confidence interval [CI] 4.3-8.2) involved a contraindicated ARV (18 non-nucleoside reverse transcriptase inhibitors), 16 involved protease inhibitors, and four involved integrase strand transfer inhibitors. The adjusted odds of receiving a contraindicated ARV were higher (3.25; 95% CI 1.40-7.57) among participants from east/central east Europe (vs. south) and lower (0.22; 95% CI 0.08-0.65) for 2015-2018 guidelines (vs. 2014). In total, 29 of the 32 (90.6%) patients receiving a contraindicated ARV and 441 of the 461 (95.7%) with potential ARV contraindications experienced a sustained virological response ≥12 weeks after stopping treatment (SVR12; p = 0.55). CONCLUSION In this large heterogenous European cohort, more than one-third of people with HIV/HCV coinfection received DAAs with potential ARV contraindications, but few received a contraindicated ARV. Use of contraindicated ARVs declined over time, corresponding to the increased availability of ARV therapy regimens without interactions with DAA across Europe. Participants who received a contraindicated DAA and ARV combination still had a high rate of SVR12

Cirrhosis and liver transplantation in patients co-infected with HIV and hepatitis B or C:an observational cohort study

This study assessed the likelihood of referral for liver transplantation assessment in a prospective cohort of patients co-infected with HIV and hepatitis B or C with complications of cirrhosis. There were 141 co-infected patients from 11 UK centres with at least one complication of cirrhosis recorded (either decompensation or hepatocellular carcinoma) out of 772 identified with cirrhosis and/or HCC. Only 23 of these 141 (16.3%) were referred for liver transplantation assessment, even though referral is recommended for co-infected patients after the first decompensation episode

The Impact of HCV Infection Duration on HIV Disease Progression and Response to cART amongst HIV Seroconverters in the UK

The effect of HCV infection on HIV disease progression remains unclear; the effect of HCV infection duration on HIV disease progression is unknown

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe