Virological Status Research Articles

Seroprevalence of Rift Valley fever virus in cattle in the Democratic Republic of the Congo.

This study aimed at assessing the serological and virological status of Rift Valley fever virus (RVFV) in cattle from four climatically diverse zones of the Democratic Republic of the Congo (DRC). A total of 1675 sera samples collected between 2014 and 2015 from cattle without clinical manifestation of RVF infection were tested using competitive and capture enzyme ELISA to detect both IgG and IgM. RT-PCR was used for the detection of nucleic acid of RVFV. Out of the 1675 cattle sera tested, 203 were found to be IgG-positive, giving an overall true seroprevalence of 12.37% (95% CI 10.86-14.05). This seroprevalence varied between the four zones with a seroprevalence of 16.16% (95% CI 12.86-20.12), 14.70% (95% CI 11.72-18.29), 10.82% (95% CI 7.19-14.19), and 7.34% (95% CI 5.13-10.41) recorded in cattle sampled in the mountainous, humid savannah, dry savannah, and forest zones, respectively (p < 0.05, χ2 = 17.26). A higher true seroprevalence of 14.58% (95% CI 9.3-22.13) was found in animals aged 1year compared to 10.43% (95% CI 8.12-13.30) and 13.16% (95% CI 11.19-15.42) in groups aged between 2-3 and > 3years, respectively, although the difference was not statistically significant (p > 0.05, χ2 = 2.95). Similarly, no statistically significant difference (p > 0.05, χ2 = 0.04) was found between the sexes of the animals. Among the IgG-positive samples screened for anti-RVFV IgM, only 1.47% (3/203) was IgM-positive. One of the IgM-positive samples was positive by RT-PCR. These findings reveal country-wide distribution of RVF in the DRC for the first time.

Diabetes is associated with advanced fibrosis and fibrosis progression in non-genotype 3 chronic hepatitis C patients

BackgroundDiabetes is a risk factor of fibrosis progression in chronic hepatitis C (CHC). However, only one longitudinal study exploring whether diabetes is associated with progression from non-cirrhotic liver to cirrhosis in CHC patients has been conducted. AimsWe investigated whether diabetes is associated with progression from non-cirrhotic liver to cirrhosis in non-genotype 3 CHC patients. MethodsA cohort consisting of 976 non-genotype 3 patients histologically proven to have CHC was studied. After excluding patients with biopsy-proven or ultrasound-identified cirrhosis, there were 684 patients without cirrhosis. All 684 patients underwent hepatocellular carcinoma surveillance using ultrasound every 6 months, with a median duration of follow-up evaluation of 102.4 months. During the follow-up period, 60 patients developed cirrhosis according to ultrasound findings. ResultsFor the subgroup of 684 patients without cirrhosis, Kaplan–Meier survival analyses showed no significantly different cumulative incidences of cirrhosis (log-rank test; P = 0.71) among the patients with diabetes as compared to those without. However, after making adjustments for age, gender, fibrosis, steatosis, sustained virological response status, and obesity using Cox’s proportional hazard model, diabetes was found to be an independent predictor for cirrhosis (HR = 1.9; 95% CI = 1.05–3.43, P = 0.03). ConclusionsDiabetes is associated with progression from non-cirrhotic liver to cirrhosis in non-genotype 3 CHC patients.

Decreasing rates of acute myocardial infarction in people living with HIV: a nationwide cohort study in Spain, 2004-2015.

Contemporary data from country-wide cohorts are needed to reveal trends in the occurrence of acute myocardial infarction (AMI) in people living with HIV (PLWH). We analysed time trends in the standardized incidence rate (sIR) of AMI in PLWH in Spain from 2004 to 2015, and compared them with trends in the general population. A longitudinal study in a nationwide contemporary multicentre HIV-infected cohort was carried out. Data on all incident AMI events were collected, and age- and sex-standardized IRs calculated. To analyse the IR of AMI in the general population, the national rates of hospital discharges for AMI per 100000 inhabitants stratified for age and sex from 2004 to 2015 were obtained using the morbidity report data from the National Statistics Institute. A Poisson regression model was fitted to assess the effect of covariates of interest on AMI occurrence. The sIRs of AMI in 2004-2015 were 237.92 [95% confidence interval (CI) 225.95-249.90] and 66.75 (95% CI: 23.49-110.01) per 100000 patient-years in male and female PLWH, respectively. There was a decrease in the sIR of AMI in male PLWH from 279.02 (95% CI: 265.46-292.59) per 100000person-years in 2004-2009 to 222.13 (95% CI: 210.83-233.42) per 100000 person-years in 2010-2015. Compared with the general population, the sIR ratio was 1.41 (95% CI: 1.26-1.55) in 2004-2009, and 1.28 (95% CI: 1.15-1.43) in 2010-2014. AMI occurrence was associated with older age (P<0.066 for each 10-year age stratum ≥35-years compared with the 25-34 year stratum), higher plasma HIV RNA (P<0.001), lower CD4 count (P<0.04 for CD4 strata >350 cells/μL compared with the 0-100 cells/μL stratum), and the period 2004-2009 (P<0.001). There has been a decreasing incidence of AMI in PLWH in Spain, associated with improving immune and virological status, but the incidence of AMI has remained higher than in the general population.

P-A7 HIV disease history in perinatally HIV infected adolescents with interrupted care

Early initiation of HAART preserves the robust immune system of perinatally HIV infected children and limits viral reservoir size. Our aim was to study the current immune and virological status of perinatally infected adolescents who returned after defaulting care. A retrospective analysis was conducted on laboratory outcomes stratified by defaulters and non-defaulters and among age bands at HAART commencement. Among 78 patients, the median age was 14 years [IQR 13,17]. HAART was commenced at a median age of 6 years [IQR 3,8] with 45 (57%) at &gt;6 years. Among 27 defaulters the median time of default was 22 months. Total time on HAART was a mean of 8.5 years ± 3 years and 56 (71%) were on protease inhibitors. Zenith HIV RNA load was a median of 4.8 log10 copies/ml [IQR 4.2–5.2]. Nadir CD4 cell count was 368 [IQR 61,648]. Median current CD4 percent was 33.5% [IQR 18,46] Duration of CD4 of 15-25% was 12 months [IQR 4, 32] for defaulters compared with 4 months [IQR 0,8] for non-defaulters. The mean duration of viral load &lt;500 copies/mL was 1.48 ± 1.68 years among defaulters, 3.6± 3.2 years among non defaulters (p &lt; 0.0001); 3.9 ± 3 for those commencing HAART at age 1-5 years, and 2.4 ± 2.6 for &gt;6 years (p &lt; 0.05). Seventy percent of adolescents commencing HAART at 1-5 years versus 43% at age &gt;6 year had a current CD4 count &gt;500 (P &lt; 0.03). Virologic suppression was 67% in the 1–5 year band versus 27% in the &gt;6 year band (p &lt; 0.0001). Defaulters and non defaulters did not differ with current virologic or immunologic markers. Late age at starting HAART had a greater negative influence on final outcome than interrupted therapy. These results suggest the potential in HIV remission research of interrupting HAART after early initiation of treatment.

CARDIAC AND INFLAMMATORY BIOMARKERS IN PERINATALLY HIV-INFECTED AND HIV-EXPOSED UNINFECTED CHILDREN

OBJECTIVES To compare distributions of serum cardiac and inflammatory biomarkers between perinatally HIV-infected (PHIV) and perinatally HIV-exposed uninfected (PHEU) children, to evaluate their associations with echocardiographic measures, and among PHIV youth, with antiretroviral therapy (ART) and HIV disease severity measures. DESIGN Cross-sectional analysis of temporally paired serum samples for biomarkers and echocardiograms in a prospective multicenter cohort study of PHIV and PHEU youth. METHODS Serum samples were analyzed among 402 youth in the PHACS Adolescent Master Protocol (AMP) for high-sensitivity cardiac troponin-T (hs-cTnT, a cardiomyocyte injury marker), N-terminal-pro-brain natriuretic peptide (NT-proBNP, a myocardial stress marker), and inflammatory markers [high-sensitivity C-reactive protein, interleukin (IL)-1, IL-6, IL-8, IL-10, IL-18, tumor necrosis factor-α (TNF-α), and soluble TNF receptor II (sTNF-RII)]. Echocardiograms were centrally measured and parameters converted to z cores to account for differences in age and body size. RESULTS Compared with PHEU (N = 156), PHIV youth (N = 246) more often had detectable hs-cTnT and higher levels of sTNF-RII and IL-18. Higher inflammatory biomarkers were generally associated with higher left ventricular (LV) wall stress and lower LV function and LV mass in the two groups. Among PHIV youth, the biomarkers were more strongly associated with current rather than historical immunologic and virologic status. CONCLUSION PHEU and PHIV have modest, significant differences in serum levels of specific inflammatory and active myocardial injury biomarkers. Higher biomarker levels were associated with lower LV mass and shifts in LV structure. Further study is warranted on the longitudinal role of cardiac and inflammatory biomarkers for targeting interventions among PHIV and PHEU youth.

Use of viral load surveillance data to assess linkage to care for persons with HIV released from corrections.

Incarcerated people remain a priority group in efforts to control and reverse the HIV epidemic. Following release, social instability and reengagement in key transmission risk behaviors increase the risk of secondary transmission of HIV. Targeted programs have been developed to facilitate reengagement in care on reentry. Evaluation of the impact of these initiatives requires a systematic, confidential, framework for assessment of linkage to care for persons released from corrections. By linking HIV viral load surveillance data to corrections release data, the time to the first laboratory monitoring service in the community as well as the virologic status can be assessed. Using this method, we linked release data for sentenced individuals released from Massachusetts state correctional facilities in 2012 to HIV surveillance data from the Massachusetts HIV/AIDS Surveillance Program (MHASP) for the years 2012–2013. We identified 41 individuals with HIV released in 2012. Ninety-one percent had identified virologic assessments post release, 41% within 30 days. Thirty-three percent did not have a viral load assessed for more than 90 days and 31% had detectable virus at the time of their initial assessment. Persons with longer incarcerations (> 180 days) were more likely to have suppressed viral load at the time of follow-up (p = 0.05). This work demonstrates the important value of HIV laboratory surveillance data and correctional release data as a tool to assess linkage to care following release from corrections. We encourage jurisdictions to explore utilizing similar methodology to evaluate the effectiveness of the linkage to HIV care after release from incarceration.

Differences in Virological and Immunological Risk Factors for Non-Hodgkin and Hodgkin Lymphoma.

Non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) are increased in populations with immune dysfunction, including people living with HIV; however, there is little evidence for to what degree immunological and virological factors differently affect NHL and HL risk. Data from the Data Collection on Adverse events of Anti-HIV Drugs Study cohort were analyzed to identify independent risk factors for NHL and HL using hazard ratios (HRs), focusing on current and cumulative area under the curve (AUC) measures of immunological and virological status. Variables with different associations with NHL and HL were identified using marginal Cox models. All statistical tests were two-sided. Among 41 420 people followed for 337 020 person-years, 392 developed NHL (incidence rate = 1.17/1000 person-years of follow-up [PYFU], 95% confidence interval [CI] = 1.06 to 1.30) and 149 developed HL (incidence rate = 0.44/1000 PYFU, 95% CI = 0.38 to 0.52). Higher risk of both NHL and HL was associated with lower current CD4 cell count (adjusted HR [aHR] of NHL for CD4 <100 vs > 599 cells/mm3 = 8.08, 95% CI = 5.63 to 11.61; HL = 4.58, 95% CI = 2.22 to 9.45), whereas higher current HIV viral load (aHR of NHL for HIV-VL >1000 vs < 50 copies/mL = 1.97, 95% CI = 1.50 to 2.59) and higher AUC of HIV-VL (aHR of NHL for highest vs lowest quintile = 2.91, 95% CI = 1.92 to 4.41) were associated with NHL only. Both current and AUC of HIV-VL were factors that had different associations with NHL and HL, where the hazard ratio for NHL was progressively higher than for HL with increasing HIV-VL category. Lower current CD4 cell count had a strong but similar association with both NHL and HL. CD4 depletion increased risk of both types of lymphomas while current and accumulated HIV-VL was associated with NHL only. This suggests that NHL development is related to both CD4 cell depletion and added immune dysfunction derived from ongoing HIV replication. This latter factor was not associated with HL risk.

Treatment of HIV and Use of HAART in HIV Infected Patients with Acute Septic Shock

BackgroundFor HIV patients admitted with sepsis, ARVs are often stopped or held due to myriad concerns including drug interactions, acute renal failure, gastrointestinal dysfunction, or inability to administer crushed medications down feeding tubes. We seek to examine prescription patterns of HAART for HIV positive patients admitted for sepsis in our healthcare system and the impact of HAART prescription on patient outcomes.MethodsWe identified HIV positive patients from an institutional database of patients admitted for sepsis within our multi-hospital healthcare system and retrospectively extracted further clinical patient and laboratory information as well as information on HAART prescription by chart review. The impact of HAART prescription and immunologic and virologic parameters of HIV infection on mortality was examined.ResultsInpatient mortality was 35% in HIV patients admitted for sepsis, compared with 17% for all patients with sepsis in our healthcare system. Opportunistic infections were identified in only 25% of patients while 56% had other infections identified. Only 55% of patients had HAART prescribed while inpatient. CD4 count, virologic suppression, APACHE score, presence of an opportunistic infection, admission to a tertiary care hospital, and inpatient prescription of HAART were all predictors of survival.Table:Factors impacting mortality in HIV patients with sepsis in univariate analysis.Survivors (n = 50)Deaths (n = 28)Odds ratio of survival (p value)Mean baseline CD4 count30964(P < 0.01)Virologic suppression (VL<200)48% (n = 21 of 44)22% (n = 5 of 23)3.3 (P < 0.05)Mean APACHE score67 (n = 32)110 (n = 17)(P < 0.01)Opportunistic infection18% (n = 9)39% (n = 11)0.34 (P < 0.05)Tertiary hospital admission50% (n = 25)21% (n = 6)3.7 (P < 0.05)Inpatient HAART prescription68% (n = 34)32% (n = 9)4.5 (P < 0.01)In a multivariable analysis both CD4 count and inpatient HAART prescription predicted survival in our cohort with an odds ratio of survival of 3.3 for patients prescribed HAART inpatient compared with their untreated peers.ConclusionImmunologic and virologic status at time of admission predicted survival in HIV patients admitted for sepsis but prescription of HAART to HIV patients admitted for sepsis may increase survival.Disclosures C. Polk, Gilead Sciences: Investigator, Research support; Viiv Healthcare: Investigator, Research support

Improved HIV-1 Viral Load Monitoring Capacity Using Pooled Testing With Marker-Assisted Deconvolution.

Improve pooled viral load (VL) testing to increase HIV treatment monitoring capacity, particularly relevant for resource-limited settings. We developed marker-assisted mini-pooling with algorithm (mMPA), a new VL pooling deconvolution strategy that uses information from low-cost, routinely collected clinical markers to determine an efficient order of sequential individual VL testing and dictates when the sequential testing can be stopped. We simulated the use of pooled testing to ascertain virological failure status on 918 participants from 3 studies conducted at the Academic Model Providing Access to Healthcare in Eldoret, Kenya, and estimated the number of assays needed when using mMPA and other pooling methods. We also evaluated the impact of practical factors, such as specific markers used, prevalence of virological failure, pool size, VL measurement error, and assay detection cutoffs on mMPA, other pooling methods, and single testing. Using CD4 count as a marker to assist deconvolution, mMPA significantly reduces the number of VL assays by 52% [confidence interval (CI): 48% to 57%], 40% (CI: 38% to 42%), and 19% (CI: 15% to 22%) compared with individual testing, simple mini-pooling, and mini-pooling with algorithm, respectively. mMPA has higher sensitivity and negative/positive predictive values than mini-pooling with algorithm, and comparable high specificity. Further improvement is achieved with additional clinical markers, such as age and time on therapy, with or without CD4 values. mMPA performance depends on prevalence of virological failure and pool size but is insensitive to VL measurement error and VL assay detection cutoffs. mMPA can substantially increase the capacity of VL monitoring.

Does rapid HIV testing result in an early diagnosis and reduce the waiting time for patients to receive medical care?

ABSTRACTThe implementation of rapid HIV testing in Brazil began in 2006 for specific groups, and from 2009 was extended to the Counseling and Testing Centers (CTC) in certain Brazilian capitals. The aim of this study was to compare two groups of individuals: those diagnosed with HIV infection by conventional testing and those diagnosed with rapid testing, with respect to: the waiting time before receiving medical care, the time of the first laboratory tests and the virological, immune and clinical status. This is a cross-sectional study to compare a group with individuals diagnosed by conventional testing (2006–2008) and another with those diagnosed by rapid testing (2010–2011).The median time between blood collection and diagnosis of HIV in the conventional test group was 76 days, while in the rapid test group 94.2% of the subjects received their results on the same day of blood collection (p < 0.001). In the conventional test group, the median period of time before the first consultation with an infectious disease specialist was 99 days, and for the rapid test group the time was 14 days (p < 0.001). The median time between the first blood sample and the first results of the CD4 count and viral load was approximately 2.5 times lower in the rapid test group (p < 0.001 for both). The median CD4 count in the rapid test group (472) was higher than in the conventional test group (397) (p = 0.01). The introduction of rapid HIV testing as a diagnostic strategy has reduced the waiting times for medical care and laboratory tests and also allowed earlier diagnosis of HIV infection than with the conventional test.

The role of the tissue factor and its inhibitor in the development of subclinical atherosclerosis in people living with HIV.

IntroductionHIV infection is associated with an increased risk of cardiovascular disease in connection with atherosclerosis and thromboembolic complications. The pathogenesis of atherosclerosis is still unclear in this group of patients. Studies on pathogenesis of atherosclerosis in the general population emphasize the role of the extrinsic pathway of blood coagulation, particularly the tissue factor (TF) and tissue factor pathway inhibitor (TFPI). The effect of persistent activation of the immune system on enhanced expression of TF on the surface of monocytes in subjects infected with HIV is known to be correlated with the level of HIV RNA in blood serum.Study aimThe aim of this study was to evaluate the concentration of TF and its inhibitor TFPI in blood plasma, the impact of traditional and non-traditional cardiovascular risk factors on their concentration and the impact of both markers of haemostasis on the severity of subclinical atherosclerosis as assessed by the intima-media measurement of the carotid artery in HIV infected patients.MaterialsThe study included 121 HIV-infected people with known clinical, immunological and virological status. The control group consisted of 42 healthy individuals, selected in terms of age and sex.Results and conclusionsHigher concentrations of TF occurred in HIV-infected patients with a low current plasma HIV RNA level, nadir CD4+ T-cell count and longer duration of cumulative antiretroviral treatment. In multivariate analysis, it was the length of cumulative NRTI treatment that impacted on the concentration of TF. The determinants of cardiovascular disease (CVD) risk factors and inflammatory markers did not show any effect on the concentrations of TF.The TFPI level in HIV-infected patients was significantly higher than in the control group and was negatively correlated with the current level of HIV RNA and nadir CD4+ T-cell count, being higher in patients subjected to antiretroviral treatment. It was shown that the higher the cardiovascular risk and the higher the levels of total cholesterol, low-density lipoprotein cholesterol (LDL) and non-high-density lipoprotein cholesterol (non-HDL), the higher the concentrations of TFPI observed. The levels of TF and TFPI were positively correlated with carotid intima media thickness (cIMT); in the multivariate analysis, TF, non-HDL cholesterol and lifetime smoking (pack-years) independently affected the growth of cIMT. A similar effect on cIMT was demonstrated by TFPI.

Plasma protein, haematologic and blood chemistry changes in African grey parrots (Psittacus erithacus) experimentally infected with bornavirus

ABSTRACTBornaviruses are considered to be the causative agent of proventricular dilatation disease (PDD) in psittacine birds. In order to detect haematological and blood chemistry changes during the development of PDD and a possible correlation with clinical signs and the virological status, six African grey parrots (Psittacus erithacus) were experimentally infected with parrot bornavirus 4 (PaBV-4) by subcutaneous route. All six parrots developed clinical signs of varying extent and successful infection was confirmed in all the birds by seroconversion or detection of RNA of the PaBV-4 infection strain. Based on population-based and intra-individual reference ranges established during 12 months prior to experimental infection, only minor haematological changes were detected in individual birds after infection. Changes in blood chemistry were restricted to aspartate aminotransferase, creatine kinase, total protein, glucose and uric acid. Plasma protein electrophoresis revealed marked changes starting 10 weeks post infection characterized by an increase in the γ-globulin fraction and a gradual decrease to normal values during weeks 22–34. Indications of an acute-phase reaction at the initial stages of infection were not detected. While three birds suffered from clinical signs of PDD, which included weight loss and neurological disorders and died before development of haematological and plasma protein changes, recovery of clinical disease was paralleled in the remaining birds by an increase in γ-globulins and bornavirus-specific antibody titres.

Candidates for inclusion in a universal antiretroviral regimen: are lamivudine and emtricitabine interchangeable?

Lamivudine (3TC) and emtricitabine (FTC) are the most widely used antiretroviral medications worldwide and are considered by the WHO to be interchangeable. This article reviews evidence supporting interchangeability of 3TC and FTC and considerations for future use. Three randomized trials have directly compared the safety and efficacy of 3TC and FTC against identical backbone regimens. Each of these trials reported a nonsignificant difference in virological suppression, and when results were pooled the overall difference was nonsignificant (relative risk 1.03, 95% confidence interval 0.96-1.10). These findings of equivalence are further supported by indirect evidence from nine randomized trials comparing 3TC and FTC against a similar backbone regimen of two different nucleoside reverse transcriptase inhibitors (relative risk of virological suppression 0.99, 95% confidence interval 0.96-1.01). Data from observational studies is mixed. Overall, reported differences between 3TC and FTC in observational studies are often associated with differences in the baseline characteristics of the treatment groups, notably with respect to immunological and virological status, comorbidity, substance misuse, and pill burden. The totality of evidence to date, from pharmacological data to observational studies to direct and indirect comparisons in randomized trials, suggests that 3TC and FTC can be considered to be therapeutically interchangeable and that if there are any differences, these are likely to be very small and not of major clinical importance.

Prevalence of HIV risk-related drug use and sexual activity among men who have sex with men attending a specialist UK club drug clinic

PurposeThe purpose of this paper is to examine patterns of drug use among a cohort of drug treatment-seeking drug-using gay men and other men who have sex with men (MSM), and whether these activities differ between, or predict, HIV status.Design/methodology/approachCross-sectional study was conducted in a specialist club drug clinic in London covering 407 consecutive attendees who identified as MSM. Substance use, including injecting drug use (IDU), associated sexual activity and self-reported HIV status were measured by clinical interview and National Drug Treatment Monitoring System data tool.FindingsOver a 45-month period, 407 MSM attended the clinic. In total, 62.1 per cent were HIV positive, 48.9 per cent had injected drugs, 14.9 per cent reported needle sharing and 73.3 per cent used drugs to facilitate sex. The most commonly reported problem drugs were GHB/GBL (54.3 per cent) methamphetamine (47.7 per cent) and mephedrone (37.8 per cent). HIV status was associated with methamphetamine, mephedrone, IDU, sharing equipment, using drugs to facilitate sex, older age and older age of drug initiation, as well as Hepatitis C virology (HCV) status. Use of methamphetamine, HCV infection, older age and IDU predicted HIV positive status in a logistic regression model.Practical implicationsThe findings describe a constellation of risk factors including high levels of IDU, sharing of equipment and high-risk sexual activity in a population with high rates of HIV positive serology. They also provide further evidence for a link between HIV infection and use of methamphetamine.Social implicationsThe authors suggest a need for greater awareness of HIV-related risk activities and promotion of HIV prevention strategies for MSM by both sexual health and drug treatment services.Originality/valueThis paper is amongst the very first studies of its nature.

Maintenance hemodialysis in Menoufia governorate, Egypt: Is there any progress?

Introduction End-stage kidney disease (ESKD) has a major health impact worldwide. Hemodialysis (HD) is the basic renal replacement therapy in our country. In Egypt, like other developing countries, there is no electronic data system that permits simple measurable examination and assurance of the span of the issue for future plans. Aim The aim of this study was to assess the prevalence of ESKD patients on HD in Menoufia governorate, Egypt, as well as the clinical characteristics of such patients to make a core for national data registry. Patients and methods A questionnaire was conducted on ESKD patients on regular HD focusing on demographic data and clinical characteristics of the dialysis population, including smoking history, causes of ESKD, virology status, vascular access, blood transfusion, hemoglobin level, calcium, phosphorus, and parathyroid hormone. Results The prevalence rate of ESKD in Menoufia governorate was 483 patients per million populations. The mean age was 53.18±13.26 years [the highest proportion of patients (36.6%) was aged between 50 and 60 years]; there were 61.6% male and 38.4% female patients. The mean duration of dialysis was 3.78±3.372 years. The main causes of ESKD were hypertension (33.4%) and diabetic nephropathy (9.2%), and the unknown etiology accounted for 32.9% of all causes of ESKD. The prevalence of hepatitis C and B was found to be 42 and 2%, respectively, whereas the prevalence of hepatitis C virus (seroconversion was 7.9%). Conclusion In Menoufia governorate, the prevalence of ESKD patients on regular HD is steadily increasing than that previously reported, especially among older patients. Hypertension and diabetes mellitus are the most commonly accounted causes of ESKD, whereas undetermined etiology accounted for 32.9%. Hepatitis C infection and seroconversion among dialysis patients have been reduced.

Predictors for HCV treatment outcome: lower limit of quantification vs. limit of detection

Introduction. In HCV treatment, the early on-treatment virological status is used as guideline for response guided therapy (RGT) and is the key predictor for a sustained virological response (SVR). The response to treatment (RT) is determined by HCV RNA results at week 4 and 12 of treatment. Being ‘undetectable’ at these time points, is a reliable predictor for reaching a SVR. To define an ‘undetectable’ HCV RNA, the lower limit of quantification (LOQ) and not the limit of detection (LOD) is used. This leaves a gray zone between the LOQ and the LOD, which results in a ‘detectable but no quantifiable’ (DNQ) HCV RNA to be reported as ‘undetectable’. The aim of this study is to analyse the reliability of using the LOQ at key decision time points, week 4 (Rapid viral response; RVR) and week 12 ( Early viral response; EVR) to predict treatment outcome. Methods. Retrospective analysis of the response to therapy, treatment outcome and SVR of patients treated for HCV. In the period Oct 2012 – Apr 2013, HCV RNA samples were conducted at week 4, 12, end of treatment (EOT) and 24 weeks after treatment and tested with the Ampliprep/Cobas-Taqman_HCV-test-v1.0. (Limit of detection; LOD: 15 IU/ml, Lower limit of quantification; LOQ: 43 IU/ml). Results. In total, 19 patients were treated, of which 10 relapsed and 9 cleared the virus. In both treatment outcome groups, DNQ HCV RNA statuses were observed. Treatment outcome showed no relation between having a DNQ during treatment (p=0,350) or at decision time points, 4th week (p=0,167) or 12th week (p=0,474). In contrast, a on-treatment viral status &gt;LOQ and &lt;LOD showed a relation with treatment outcome at week 4 (p=0,007), but not at week 12 (p=0,474). In addition, the response to therapy (RVR or EVR) showed a relation with reaching SVR (p=0,023), which was not influenced by the on-treatment viral status; DNQ. Conclusion. Reaching an ‘undetectable’ HCV RNA result at week 4 and/or week 12, is not always a guarantee of achieving SVR. In our study, being ‘detectable but not quantifiable’ at decision time point does not give a higher incidence of relapsing. The HCV RNA being ‘detectable but not quantifiable’ does not influence the predictive value of a Rapid or Early viral response. Therefore, our study suggests that no alterations in the decision-rules for HCV guidelines have to be carried out.

Alarmins and central nervous system inflammation in HIV-associated neurological disorders.

In the era of highly active antiretroviral therapy (HAART), HIV-1-associated neurocognitive disorders (HAND) persist in infected individuals with adequate immunological and virological status. Risk factors for cognitive impairment include hepatitis C virus co-infection, host genetic factors predisposing to HAND, the early establishment of the virus in the CNS and its persistence under HAART; thus, the CNS is an important reservoir for HIV. Microglial cells are permissive to HIV-1, and NLRP3 inflammasome-associated genes were found expressed in brains of HIV-1-infected persons, contributing to brain disease. Inflammasomes can be triggered by alarmins or danger-associated molecular patterns (DAMPs), which directly stimulate the production of proinflammatory mediators by glial cells, contribute to blood-brain barrier injury through induction of release of various proteases and allow the passage of infected macrophages, and trigger IL-1β release from primed cells. Amongst alarmins involved in HIV-1-induced neuropathogenesis, IL-33 and high-mobility group box 1 (HMGB1) are of particular interest. Neurocognitive alterations were recently associated with dysregulation of the IL-33/ST2 axis in the CNS, leading to the induction of neuronal apoptosis, decrease in synaptic function and neuroinflammation. Specific biomarkers, including HMGB1 and anti-HMGB1 antibodies, have been identified in cerebrospinal fluid from patients with HAND, correlated with immune activation and identifying a very early stage of neurocognitive impairment that precedes changes in metabolites detected by magnetic resonance spectroscopy. Moreover, HMGB1 plays a crucial role in HIV-1 persistence in dendritic cells and in the constitution of viral reservoirs. In this review, the mechanisms whereby alarmins contribute to HIV-1-induced CNS inflammation and neuropathogenesis will be discussed.

Plasma CXCL10, sCD163 and sCD14 Levels Have Distinct Associations with Antiretroviral Treatment and Cardiovascular Disease Risk Factors.

We investigate the associations of three established plasma biomarkers in the context of HIV and treatment-related variables including a comprehensive cardiovascular disease risk assessment, within a large ambulatory HIV cohort. Patients were recruited in 2010 to form the Royal Perth Hospital HIV/CVD risk cohort. Plasma sCD14, sCD163 and CXCL10 levels were measured in 475 consecutive patients with documented CVD risk (age, ethnicity, gender, smoking, blood pressure, BMI, fasting metabolic profile) and HIV treatment history including immunological/virological outcomes. The biomarkers assessed showed distinct associations with virological response: CXCL10 strongly correlated with HIV-1 RNA (p<0.001), sCD163 was significantly reduced among ‘aviraemic’ patients only (p = 0.02), while sCD14 was unaffected by virological status under 10,000 copies/mL (p>0.2). Associations between higher sCD163 and protease inhibitor therapy (p = 0.05) and lower sCD14 with integrase inhibitor therapy (p = 0.02) were observed. Levels of sCD163 were also associated with CVD risk factors (age, ethnicity, HDL, BMI), with a favourable influence of Framingham score <10% (p = 0.04). Soluble CD14 levels were higher among smokers (p = 0.002), with no effect of other CVD risk factors, except age (p = 0.045). Our findings confirm CXCL10, sCD163 and sCD14 have distinct associations with different aspects of HIV infection and treatment. Levels of CXCL10 correlated with routinely monitored variables, sCD163 levels reflect a deeper level of virological suppression and influence of CVD risk factors, while sCD14 levels were not associated with routinely monitored variables, with evidence of specific effects of smoking and integrase inhibitor therapy warranting further investigation.

Evolution of hepatitis C virus in HIV coinfected patients under antiretroviral therapy

Five patients (P) were followed-up for an average of 7.73years after highly active antiretroviral therapy (HAART) initiation. Patients' immune and virological status were determined by periodical CD4+T-cell counts and HIV and HCV viral load. HCV populations were studied using longitudinal high throughput sequence data obtained in parallel by virological and immunological parameters. Two patients (P7, P28) with sub-optimal responses to HAART presented HCV viral loads significantly higher than those recorded for two patients (P1, P18) that achieved good responses to HAART. Interestingly, HCV populations from P7 and P28 displayed a stable phylogenetic structure, whereas HCV populations from P1 and P18showeda significant increase in their phylogenetic structure, followed by a decrease after achieving acceptable CD4+T-cell counts (>500 cell/μl). The fifth patient (P25) presented high HCV viral loads, preserved CD4+T-cell counts from baseline and all along the follow-up, and displayed a constant viral phylogenetic structure. These results strongly suggest that HAART-induced immune recovery induces a decrease in HCV viral load and an increase in the HCV population phylogenetic structure likely reflecting the virus diversification in response to the afresh immune response. The relatively low HCV viral load observed in the HAART responder patients suggests that once HCV is adapted it reaches a maximum number of haplotypes higher than that achieved during the initial stages of the immune response as inferred from the two recovering patients. Future studies using larger number of patients are needed to corroborate these hypotheses.

Incidence and Risk Factors for Severe Bacterial Infections in People Living with HIV. ANRS CO3 Aquitaine Cohort, 2000-2012.

Severe non-AIDS bacterial infections (SBI) are the leading cause of hospital admissions among people living with HIV (PLHIV) in industrialized countries. We aimed to estimate the incidence of SBI and their risk factors in a large prospective cohort of PLHIV patients over a 13-year period in France. Patients followed up in the ANRS CO3 Aquitaine cohort between 2000 and 2012 were eligible; SBI was defined as a clinical diagnosis associated with hospitalization of ≥48 hours or death. Survival analysis was conducted to identify risk factors for SBI.Total follow-up duration was 39,256 person-years [PY] (31,370 PY on antiretroviral treatment [ART]). The incidence of SBI decreased from 26.7/1000 PY [95% CI: 22.9–30.5] over the period 2000–2002 to 11.9/1000 PY [10.1–13.8] in 2009–2012 (p <0.0001). Factors independently associated to increased risk of SBI were: plasma HIVRNA>50 copies/mL (Hazard Ratio [HR] = 5.1, 95% Confidence Interval: 4.2–6.2), CD4 count <500 cells/mm3 and CD4/CD8 ratio <0.8 (with a dose-response relationship for both markers), history of cancer (HR = 1.4 [1.0–1.9]), AIDS stage (HR = 1.7 [1.3–2.1]) and HCV coinfection (HR = 1.4, [1.1–1.6]). HIV-positive patients with diabetes were more prone to SBI (HR = 1.6 [0.9–2.6]). Incidence of SBI decreased over a 13-year period due to the improvement in the virological and immune status of PLHIV on ART. Risk factors for SBI include low CD4 count and detectable HIV RNA, but also CD4/CD8 ratio, HCV coinfection, history of cancer and diabetes, comorbid conditions that have been frequent among PLHIV in recent years.