High VL Research Articles

P-452. Factors Associated with Liver Fibrosis Development in HIV-Monoinfected Patients Within the Modern ART Era

Abstract Background Liver fibrosis (LF) is a significant contributor to morbidity and mortality in people living with HIV (PLWH). Using data from the US Military HIV Natural History Study (NHS), we examined prevalence and risk factors of LF in the era of fixed dose combination antiretroviral therapy (ART).Table 1.Pertinent Participant Characteristics Categorized by the Presence or Absence of Liver Fibrosis: Methods The NHS is comprised of military beneficiaries with HIV, who are often diagnosed and treated early due to mandatory screening and guideline-based initiation of ART. We included ART-treated NHS participants, diagnosed after 2006, without active hepatitis B or C infection. LF was defined as a FIB-4 Index >2.67, a validated, non-proprietary, readily available marker of LF based on age, platelets, and liver-associated enzymes. Risk factors examined included demographic, HIV-specific, and other recognized associations with LF, see Table 1 footnote for details. Participants characteristics were analyzed with either the Kruskal Wallis or Chi2 test. Cox proportional hazard models, adjusted for baseline and time-updated variables, were used to assess risk factors for developing LF.Table 2.Unadjusted and adjusted HR on liver fibrosis Results Among 1209 participants, followed for a median of 5.4 years, 60 (5.0%) met the criteria for LF. Overall, the median time to ART initiation was 2.4 months. The median time to LF was 2.5 years. At LF diagnosis the median age, CD4 count and viral load were 36 years, 526 cells/uL and 20 copies/mL respectively. Those with LF were older, had lower CD4 count and high VL at HIV diagnosis and more likely to initiate NNRTI based ART, table 1. In an adjusted model, LF was associated with female gender, hypertension, obesity, at risk drinking, and higher VL, while African American race, integrase strand transfer inhibitor (INSTI) use, and higher CD4 counts were protective, table 2. Conclusion In the contemporary ART era, in this young and promptly treated cohort, the prevalence of LF was 5%, suggesting liver-related morbidity remains an important concern. Our results underscore the protective effect of immune preservation (by timely initiation and continuation of ART) against LF; however, the observed protective association with INSTI-based regimens will need further study to determine long-term benefit. As observed previously, hypertension, at risk drinking, and obesity are modifiable risk factors that should be addressed. Disclosures All Authors: No reported disclosures

An epidemiological and spatiotemporal analysis of visceral leishmaniasis in West Pokot, Kenya, between 2018 and 2022

BackgroundVisceral leishmaniasis (VL) remains a significant public health concern in West Pokot County, Kenya, where a large outbreak between 2020 and 2022 emphasised the need for improved VL control strategies. However, these measures are partially hampered by limited insight into the geographical distribution of cases and localised outbreaks of the disease. This study aimed to describe the epidemiology and spatiotemporal patterns of VL in West Pokot between 2018 and 2022, in order to map the spread of VL transmission and identify regions that should be prioritised for control interventions.MethodsVL patient demographics and village of residence were retrieved from admission records of Kacheliba Sub-County Hospital in West Pokot, Kenya. The temporal trend in VL admissions between 2018 and 2022 was analysed using seasonal decomposition analysis. To describe the spatial distribution of VL cases, geographic coordinates of villages of residence were collected from pre-established databases, and VL incidence was mapped at the sub-location level. Hotspot analysis was performed per study year to identify villages with high VL incidence, and scan statistics were applied to detect spatiotemporal clusters of VL cases during the study period.ResultsA total of 1948 VL patients were reported between 2018 and 2022. The annual number of cases increased from 245 in 2019 to 598 in 2022, and VL admissions were generally higher at the start of the wet seasons. 70% of the VL cases could be georeferenced, and mapping of VL incidence revealed high case rates in the east of West Pokot during the complete study period. The eastern villages Lotongot and Chepaywat were marked as VL hotspots at a 99% confidence level in all study years. In addition, five significant spatiotemporal clusters were detected in the east and north, suggestive of local VL outbreaks in these regions.ConclusionsThe increase in VL hospital admissions during the study period stresses the need for enhanced VL control and outbreak mitigation in West Pokot. These control measures should be focused on the hotspot regions in the east of the county.

Standardized enhanced adherence counseling for improved HIV viral suppression among children and adolescents in Homa Bay and Turkana Counties, Kenya.

Viral suppression is suboptimal among children and adolescents on antiretroviral therapy (ART) in Kenya. We implemented and evaluated a standardized enhanced adherence counseling (SEAC) package to improve viral suppression in children and adolescents with suspected treatment failure in Homa Bay and Turkana. The SEAC package, implemented from February 2019 to September 2020, included: standard procedures operationalizing the enhanced adherence counseling (EAC) process; provider training on psychosocial support and communication skills for children living with HIV and their caregivers; mentorship to providers and peer educators on EAC processes; and individualized case management. We enrolled children and adolescents aged 0 to 19 years with suspected treatment failure (viral load [VL] >1000 copies/mL) who received EAC before standardization as well as those who received SEAC in a pre-post evaluation of the SEAC package conducted in 6 high-volume facilities. Pre-post standardization comparisons were performed using Wilcoxon-Mann-Whitney and Pearson’s chi-square tests at a 5% level of significance. Multivariate logistic regression was performed to identify factors associated with viral resuppression. The study enrolled 741 participants, 595 pre- and 146 post-SEAC implementation. All post-SEAC participants attended at least 1 EAC session, while 17% (n = 98) of pre-SEAC clients had no record of EAC attendance. Time to EAC following the detection of high VL was reduced by a median of 8 days, from 49 (interquartile range [IQR]: 23.0–102.5) to 41 (IQR: 20.0–67.0) days pre- versus post-SEAC (P = .006). Time to completion of at least 3 sessions was reduced by a median of 12 days, from 59.0 (IQR: 36.0–91.0) to 47.5 (IQR: 33.0–63.0) days pre- versus post-SEAC (P = .002). A greater percentage of clients completed the recommended minimum 3 EAC sessions at post-SEAC, 88.4% (n = 129) versus 61.1% (n = 363) pre-SEAC, P < .001. Among participants with a repeat VL within 3 months following the high VL, SEAC increased viral suppression from 34.6% (n = 76) to 52.5% (n = 45), P = .004. Implementation of the SEAC package significantly reduced the time to initiate EAC and time to completion of at least 3 EAC sessions, and was significantly associated with viral suppression in children and adolescents with suspected treatment failure.

Determinants of viral load status among HIV positive children on ART at Zewditu Memorial Hospital, Addis Ababa: A case control study

Introduction: Human Immunodeficiency Virus causes an immense amount of problems throughout the world, especially in sub-Saharan countries. Recently viral load is thought to be a good indicator in assessing HIV progression. Complementary feeding practice and type of complementary food are the major factors that affect VL Status. However, in Ethiopia there is paucity of evidence on the factors that could affect viral load among HIV exposed infants. Therefore, this study aimed to identify factors that affect VL Status among HIV positive children on ART at Zewditu Memorial Hospital (ZMH), Addis Ababa, Ethiopia using a case control study design. Methods: Institution based unmatched case- control study was employed among a total of 241 (71 cases and 170 controls) children attending for follow up in ZMH ART clinic from July to August 2020. The interviewer conducts a face-to-face interview for 24 hour’s dietary diversity from mothers using standardized and pre tested questioner. SPSS 20 was used for data entry and cleaning, while Stata 14 was used for data analysis. Backward stepwise logistic regression analysis was used to determine the association of the factors with the outcome variable. A P-value ≤ 0. 05 was considered statistically significant at 95% confidence level throughout the study. Result: Out of 241 children, 71 of them had high VL status, while the rest 170 of them had low VL status. Poor dietary diversity increases the risk of high VL on ART children [AOR= 4. 37, 95% CI: 2. 12-10. 71]. The risk of high VL increase on children whose mother’s marital status was single [AOR=4, 95% CI: 1. 40, 9. 70], among children who have a daily laborer mothers [AOR= 10. 6, 95% CI: 3. 20, 21. 67], and working on nongovernmental organizations [AOR=5. 32, 95% CI: 1. 68, 10. 51]. Children on WHO clinical stage 3 and 4 [AOR =15. 22, 95% CI: 4. 1, 39. 41], those children who started complementary feeding lately (after 6 months) [AOR= 4. 69, 95% CI: 2. 35, 13. 6] and children with poor Infant dietary diversity score [ AOR= 4. 37, 95% CI: 2. 12-10. 71]. Conclusion: Maternal marital status, maternal occupation, WHO clinical stage, late initiation of complementary feeding practice, and infant dietary diversity score are the factors affecting VL status in HIV positive children on ART at Zewditu memorial hospital.

Higher Risk of Mortality and Virologic Failure in HIV-Infected Patients With High Viral Load at Antiretroviral Therapy Initiation: An Observational Cohort Study in Chongqing, China.

BackgroundViral load (VL) is a strong predictor of human immunodeficiency virus (HIV) disease progression. The aim of this study was to evaluate the effect of high baseline VL on antiretroviral therapy (ART) outcomes among HIV-infected patients.MethodsThis retrospective study observed HIV-infected patients who had baseline VL test at ART initiation between 2015 and 2019 in Chongqing, China. Cox proportional hazards regression and logistic regression models were used to evaluate the effects of baseline VL on Acquired immunodeficiency syndrome (AIDS)-related mortality and virologic failure, respectively.ResultsThe cohort included 7,176 HIV-infected patients, of whom 38.7% had a baseline VL ≥ 100,000 copies/mL. Of the patients who died during follow-up, 58.9% had a baseline VL ≥ 100,000 copies/mL. Compared with a baseline VL < 10,000 copies/mL, ART initiation at VL ≥ 100,000 copies/mL was significantly associated with the AIDS-related death (adjusted hazard ratio, AHR = 1.4) and virologic failure (adjusted odds ratio, AOR = 2.4). Compared with patients with a baseline VL < 10,000 copies/mL, patients on the recommended first-line regimen with a VL ≥ 100,000 copies/mL at ART initiaition had higher mortality rate (5.1 vs. 1.7 per 100 person-years), but there was no significant difference in the mortality accoding to the initial VL level among patients on second-line ART (2.8 vs. 2.7 per 100 person-years). ART initiation ≤ 30 days after HIV diagnosis was associated with a lower risk of AIDS-related death (AHR = 0.6).ConclusionsART initiation with VL ≥ 100,000 copies/mL was associated with a significantly greater risk of mortality and virologic failure. Optimizing the ART regimen and initiating ART early may help to reduce mortality effectively among patients with a high baseline VL. VL testing for all HIV patients is recommended at HIV diagnosis or on ART initiation.

Thermodynamic Assessment of the Partitioning of Acetone between Supercritical CO2 and Polystyrene Using the Polar PC-SAFT Equation of State

Supercritical carbon dioxide (scCO2) has gained considerable attention in the process industry due to its favorable economic, environmental, and technical characteristics. Polymer processing is one of the key industrial applications where scCO2 plays an important role. In order to be able to efficiently design the polymer processing equipment, understanding the phase behavior and partition of solutes between scCO2 and polymers is necessary. This paper investigates the partitioning of acetone – a conventional polar cosolvent – between scCO2 and polystyrene – a glassy polymer. We highlight the importance of taking into account the polar interactions between acetone molecules and their role in the polymer phase behavior. The system is modeled under a wide range of temperatures and pressures (278.15–518.2 K and 1.0–20.0 MPa) using the polar version of the perturbed chain statistical associating fluid theory (polar PC-SAFT) equation of state. The results show that at relatively low pressure, the system exhibits a vapor–liquid–liquid (VLL) three-phase region bounded by two two-phase regions (VL and LL). At high pressure, VLL and VL regions disappear and only the LL region remains. The temperature effect is more interesting, showing a transition of upper critical solution temperature behavior to lower critical solution temperature behavior at 10 MPa and 398.15 K. It is found that neglecting the polar term can lead to significant changes in the description of the polymeric-system phase behavior especially at lower temperatures. No such differences are observed at higher temperatures (above 500 K) where the effect of polar interaction is considerably weaker.

Abstract WMP55: HIV Viral Load and Stroke Risk

Background: Among people living with HIV (PLWH), elevated plasma HIV RNA (viral load, [VL]), indicative of increased inflammation, may be associated with greater risk of stroke. Methods: Among adult PLWH receiving clinical care at six Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) sites across the U.S. from January 2006 through January 2015, first ischemic or hemorrhagic stroke was identified from adjudicated clinical events. We considered baseline and time-updated VL. Baseline viral load was defined as the most recent viral load before 2006 or at CNICS cohort entry (if after 2006). Cox proportional hazards models were used to assess the relationship between baseline VL and time-updated VL and stroke. We estimated hazard ratios for risk of stroke (all stroke, and ischemic and hemorrhagic stroke separately) comparing the 75 th percentile of VL (“high VL”) to the 25 th percentile (“low VL”). All models were adjusted for age, sex, race/ethnicity, CNICS site, diabetes, treated hypertension, statin use, smoking, nadir CD4, BMI, hepatitis C virus coinfection, and baseline ART use. The hemorrhagic stroke model was also adjusted for FIB-4. Results: Among 16,648 PLWH over an average follow-up of 4.7 years, there were 146 total strokes (119 ischemic; 19 hemorrhagic). At baseline, the median VL was 41 copies/mL (IQR: 24, 3860). Individuals with high baseline VL were 1.57 times more likely to have a stroke than individuals with low baseline VL (95% CI: 1.22, 2.04). In addition, high baseline VL was associated with increased risk of ischemic stroke (HR: 1.48; 95% CI: 1.11, 1.97) and hemorrhagic stroke (HR: 2.5; 95% CI: 1.25, 4.98). The HR for all strokes comparing high VL and low VL individuals using time-updated VL was 1.84 (95% CI: 1.42-2.40). Conclusion: Our findings suggest that higher VL is associated with stroke risk after adjusting for traditional stroke risk factors, and may have a greater impact on incidence of hemorrhagic stroke. In addition to reducing HIV-related morbidity and mortality, improving HIV care may also reduce stroke risk.

Real-world efficacy and safety of immune checkpoint inhibitors in advanced hepatocellular carcinoma: Experience of a tertiary Asian center.

559 Background: Immune checkpoint inhibitor (ICI) use in advanced hepatocellular carcinoma (HCC) is increasing. Real-world data on efficacy and safety however is lacking, more so when used in patients who fall out of standard clinical trial criteria. Methods: We conducted a retrospective review of all patients with advanced HCC seen at our centre who received at least one dose of an ICI between May 2015 - June 2018. Data cutoff was 31 Dec 2018. Responses were evaluated using RECIST v1.1 criteria. Results: 114 patients fulfilled inclusion criteria. Median age was 66 years and 88.6% were male. 96.5% had an ECOG PS of 0 – 1. 64.9% received an ICI within a clinical trial setting. 62.3% received monotherapy ICI. 19.6% of patients had Child-Pugh B disease on initiation of ICI, and 69.3% had an ALBI Grade of 2. 50.0% were known to have hepatitis B and 11.4% had hepatitis C. Baseline HBV VL ranged from undetectable to 8210000 IU/mL. 30.7% received prior systemic treatment, most commonly sorafenib (82.9%). Over a median follow-up duration of 5.7 months (0.03 - 42.4), ORR was 18.4%, and disease control rate (DCR) was 51.8%. Median PFS was 2.6 months (1.7 - 3.9), and median OS was 13.9 months (7.0 - 16.2). 5 patients (23.8%) had response duration of more than 18 months. 35.1% received further systemic therapy after ICI. On multivariable analyses, age ≥ 65 years, higher albumin level and lower bilirubin level were associated with increased OS. 68.0% of patients experienced adverse events (AEs) of any grade, 12.0% of these being grade 3 - 4. No grade 5 adverse events were observed. Use of antiviral therapy was associated with a lower risk of hepatic AEs (p = 0.04) whilst high baseline HBV VL was not associated with an increased risk of reactivation or hepatic AEs. Conclusions: In the real-world setting, responses and adverse event profiles to ICI use are comparable to those observed in clinical trials despite a more heterogenous population base. The expansion of indications for ICI use in advanced HCC beyond current approvals warrants greater study.

Undetectable Hepatitis C Viral Load Is Associated With Improved Outcomes Following Total Joint Arthroplasty

BackgroundPrevious reports establish that infection with hepatitis C virus (HCV) predisposes total joint arthroplasty (TJA) recipients to poor postoperative outcomes. The purpose of the present study is to assess whether variation in HCV VL influences perioperative outcomes following TJA. MethodsA multicenter retrospective review of all patients diagnosed with HCV who underwent primary TJA between January 2005 and April 2018 was conducted. Patients were stratified into 2 cohorts: (1) patients with an undetectable VL (U-VL) and (2) patients with a detectable VL (D-VL). Kaplan-Meier survivorship analysis was calculated with revision TJA as the end point. Subanalysis on the VL profile was done. ResultsA total of 289 TJAs were included (U-VL:118 TJAs; D-VL:171 TJAs). Patients in the D-VL cohort had longer operative times (133.9 vs 109.2 minutes), higher intraoperative blood loss (298.4 vs 219.5 mL), longer inpatient hospital stays (4.0 vs 2.9 days), more postoperative infections (11.7% vs 4.2%), and an increased risk for revision TJA (12.9% vs 5.1%). Kaplan-Meier demonstrated that the U-VL cohort trended toward better survivorship (P = .17). On subanalysis of low and high VL, no difference in outcomes was appreciated. ConclusionTJA recipients with a detectable HCV VL have longer operative times, experience more intraoperative blood loss, have longer hospital length of stay, and are more likely to experience infection and require revision TJA. The blood loss, hospital length of stay, and revision rate findings should be interpreted with caution, however, as there are confounding factors. Our findings suggest that HCV VL is a modifiable risk factor that, can reduce the risk of infection and revision surgery. Additionally, serum HCV VL was not correlated with outcomes.

Predictors of early mortality and effectiveness of antiretroviral therapy in TB-HIV patients from Brazil.

BackgroundThe implementation of antiretroviral (ARV) therapy caused a significant decrease in HIV-associated mortality worldwide. Nevertheless, mortality is still high among people living with HIV/AIDS and tuberculosis (TB). ARV-naïve HIV patients coinfected with tuberculosis (TB) have more options to treat both diseases concomitantly. Nevertheless, some TB-HIV patients undertaking ARVs (ARV-experienced) are already failing the first line efavirenz-based regimen and seem to display different response to second line ARV therapy and exhibit other predictors of mortality.MethodsWe performed a retrospective cohort study including 273 patients diagnosed with TB-HIV and treated at a referral center in Rio de Janeiro, Brazil, between 2008 and 2016. Multivariate analysis and Cox regression models were used to evaluate the effectiveness of ARV therapy regimens (viral load [VL] <80 copies from the 4th to 10th months after TB therapy introduction) and to identify predictors of early mortality (100 days after TB therapy initiation) considering ARV-naïve and ARV-experienced patients adjusting for sociodemographic, clinical and therapeutic covariates.FindingsSurvival analysis included 273 patients, out of whom 154 (56.4%) were ARV-naïve and 119 (43.6%) were ARV-experienced. Seven deaths occurred within 6 months of anti-TB treatment, 4 in ARV-naïve and 3 in ARV-experienced patients. Multivariate analysis revealed that in ARV-naïve patients, the chance of death was substantially higher in patients who developed immune reconstitution inflammatory syndrome during the study follow up (HR = 40.6, p<0.01). For ARV-experienced patients, similar analyses failed to identify factors significantly associated with mortality. Variables independently associated with treatment failure for the ARV-naïve group were previous TB (adjusted OR [aOR] = 6.1 p = 0.03) and alcohol abuse (aOR = 3.7 p = 0.01). For ARV-experienced patients, a ritonavir boosted. Protease Inhibitor-based regimen resulted in a 2.6 times higher risk of treatment failure compared to the use of efavirenz based ARV regimens (p = 0.03) and High baseline HIV VL (p = 0.03) were predictors of treatment failure.ConclusionsRisk factors for mortality and ARV failure were different for ARV-naïve and ARV-experienced patients. The latter patient group should be targeted for trials with less toxic and rifampicin-compatible drugs to improve TB-HIV treatment outcomes and prevent death.

Depression preceding Parkinson's disease: Risk factor or early symptom?

Previous reports establish that infection with hepatitis C virus (HCV) predisposes total joint arthroplasty (TJA) recipients to poor postoperative outcomes. The purpose of the present study is to assess whether variation in HCV VL influences perioperative outcomes following TJA.A multicenter retrospective review of all patients diagnosed with HCV who underwent primary TJA between January 2005 and April 2018 was conducted. Patients were stratified into 2 cohorts: (1) patients with an undetectable VL (U-VL) and (2) patients with a detectable VL (D-VL). Kaplan-Meier survivorship analysis was calculated with revision TJA as the end point. Subanalysis on the VL profile was done.A total of 289 TJAs were included (U-VL:118 TJAs; D-VL:171 TJAs). Patients in the D-VL cohort had longer operative times (133.9 vs 109.2 minutes), higher intraoperative blood loss (298.4 vs 219.5 mL), longer inpatient hospital stays (4.0 vs 2.9 days), more postoperative infections (11.7% vs 4.2%), and an increased risk for revision TJA (12.9% vs 5.1%). Kaplan-Meier demonstrated that the U-VL cohort trended toward better survivorship (P = .17). On subanalysis of low and high VL, no difference in outcomes was appreciated.TJA recipients with a detectable HCV VL have longer operative times, experience more intraoperative blood loss, have longer hospital length of stay, and are more likely to experience infection and require revision TJA. The blood loss, hospital length of stay, and revision rate findings should be interpreted with caution, however, as there are confounding factors. Our findings suggest that HCV VL is a modifiable risk factor that, can reduce the risk of infection and revision surgery. Additionally, serum HCV VL was not correlated with outcomes.

Hepatitis C in Laos: A 7-Year Retrospective Study on 1765 Patients.

Hepatitis C virus (HCV) is a global health concern, notably in Southeast Asia, and in Laos the presentation of the HCV-induced liver disease is poorly known. Our objective was thus to describe a comprehensive HCV infection pattern in order to guide national health policies. A study on a group of 1765 patients formerly diagnosed by rapid test in health centres was conducted at the Centre of Infectiology Lao Christophe Merieux in Vientiane. The demographic information of patients, their infection status (viral load: VL), liver function (aminotransferases) and treatments were analysed. Results showed that gender distribution of infected people was balanced; with median ages of 53.8 for men and 51.6years for women (13-86years). The majority of patients (72%) were confirmed positive (VL > 50IU/mL) and 28% of them had high VL (> 6log10). About 23% of patients had level of aminotransferases indicative of liver damage (> 40IU/mL); but less than 20% of patients received treatment. Patients rarely received a second sampling or medical imaging. The survey also showed that cycloferon, pegylated interferon and ribavirin were the drugs prescribed preferentially by the medical staff, without following any international recommendations schemes. In conclusion, we recommend that a population screening policy and better management of patients should be urgently implemented in the country, respecting official guidelines. However, the cost of biological analysis and treatment are significant barriers that must be removed. Public health resolutions should be immediately enforced in the perspective of meeting the WHO HCV elimination deadline by 2030.

Short Communication: Nucleoside Reverse Transcriptase Inhibitors with Reduced Predicted Activity Do Not Impair Second-Line Therapy with Lopinavir/Ritonavir or Darunavir/Ritonavir.

Second-line therapy randomized trials with lopinavir/ritonavir question the value of resistance testing to guide nucleoside reverse transcriptase inhibitor (NRTI) selection. In this study, we investigated the association between baseline drug resistance and treatment outcome after 104 weeks of second-line therapy with NRTIs and either darunavir/ritonavir or lopinavir/ritonavir in West-central Africa. We did an observational analysis of data from 387 individuals in a randomized, open-label 2LADY trial in Burkina Faso, Cameroon, and Senegal. We modeled the association between RTI drug resistance mutations (DRMs) and virological failure (VF) (viral load [VL] <50 copies/mL) at week 104 using logistic regressions. Covariates included baseline VL and CD4+ count, demographic, and adherence data. Overall, 193 (49.9%), 150 (38.8%), and 44 (11.4%) individuals had, respectively, low/none (genotypic susceptibility score [GSS] <1), intermediate (GSS = 1), and high predicted NRTI activity (GSS >1) in their prescribed second-line regimen. The average number of DRMs by drug class, the proportion of individuals by GSS category, and the duration of first-line therapy were not associated with VF (p > .05). High VL at switch was the only consistent prognostic factor for VF after multivariate adjustment (p < .01). Suboptimal adherence, high predicted RTI activity, or low NRTI mutations were associated with VF (p < .05) when using higher end points for VF or in the intention-to-treat analysis. In conclusion, the use of RTIs with predicted reduced activity does not impair second-line protease inhibitor-based therapy. Therefore, HIV care in resource-limited settings should prioritize strategies to improve adherence and targeted VL testing over drug resistance testing for selecting NRTIs during a protease-based second-line switch.

Validation of rK39 immunochromatographic test and direct agglutination test for the diagnosis of Mediterranean visceral leishmaniasis in Spain.

BackgroundVisceral leishmaniasis (VL), the most severe form of leishmaniasis, is endemic in Europe with Mediterranean countries reporting endemic status alongside a worrying northward spread. Serological diagnosis, including immunochromatographic test based on the recombinant antigen rK39 (rK39-ICT) and a direct agglutination test (DAT) based on the whole parasite antigen, have been validated in regions with high VL burden, such as eastern Africa and the Indian subcontinent. To date, no studies using a large set of patients have performed an assessment of both methods within Europe.Methodology/Principal findingsWe selected a range of clinical serum samples from patients with confirmed VL (including HIV co-infection), Chagas disease, malaria, other parasitic infections and negative samples (n = 743; years 2009–2015) to test the performance of rK39-ICT rapid test (Kalazar Detect Rapid Test; InBios International, Inc., USA) and DAT (ITM-DAT/VLG; Institute of Tropical Medicine Antwerp, Belgium). An in-house immunofluorescence antibody test (IFAT), was included for comparison. Estimated sensitivities for rK39-ICT and DAT in HIV-negative VL patients were 83.1% [75.1–91.2] and 84.2% [76.3–92.1], respectively. Sensitivity was reduced to 67.3% [52.7–82.0] for rK39 and increased to 91.3% [82.1–100.0] for DAT in HIV/VL co-infected patients. The in-house IFAT was more sensitive in HIV-negative VL patients, 84.2% [76.3–92.1] than in HIV/VL patients, 79.4% [73.3–96.2]. DAT gave 32 false positives in sera from HIV-negative VL suspects, compared to 0 and 2 for rK39 and IFAT, respectively, but correctly detected more HIV/VL patients (42/46) than rK39 (31/46) and IFAT (39/46).Conclusions/SignificanceThough rK39-ICT and DAT exhibited acceptable sensitivity and specificity a combination with other tests is required for highly sensitive diagnosis of VL cases in Spain. Important variation in the performance of the tests were seen in patients co-infected with HIV or with other parasitic infections. This study can help inform the choice of serological test to be used when screening or diagnosing VL in a European Mediterranean setting.

Quality of life among HIV-infected individuals failing first-line antiretroviral therapy in resource-limited settings

ABSTRACTWe evaluated health-related quality of life (QoL) in HIV infection participants with virologic failure (VF) on first-line antiretroviral therapy (ART) in 9 resource-limited settings (RLS). ACTG SF-21 was completed by 512 participants at A5273 study entry; 8 domains assessed: general health perceptions (GHP), physical functioning (PF), role functioning (RF), social functioning (SF), cognitive functioning (CF), pain (P), mental health (MH), and energy/fatigue (E/F); each was scored between 0 (worst) to 100 (best). Mean QoL scores ranged from 67 (GHP) to 91 (PF, SF, CF). QoL varied by country; high VL and low CD4 were associated with worse QoL in most domains, except RF (VL only), SF (CD4 only) and CF (neither). Number of comorbidities, BMI and history of AIDS were associated with some domains. Relationships between QoL and VL varied among countries for all domains. The association of worse disease status with worse QoL may reflect low QoL when ART was initiated and/or deterioration associated with VF.

Cigarette smoking is associated with high HIV viral load among adults presenting for antiretroviral therapy in Vietnam

High HIV viral load (VL >100,000 cp/ml) is associated with increased HIV transmission risk, faster progression to AIDS, and reduced response to some antiretroviral regimens. To better understand factors associated with high VL, we examined characteristics of patients presenting for treatment in Hanoi, Vietnam. We examined baseline data from the Viral Load Monitoring in Vietnam Study, a randomized controlled trial of routine VL monitoring in a population starting antiretroviral therapy (ART) at a clinic in Hanoi. Patients with prior treatment failure or ART resistance were excluded. Characteristics examined included demographics, clinical and laboratory data, and substance use. Logistic regression was used to calculate crude and adjusted odds ratios (aOR) and 95% confidence intervals (95% CI). Out of 636 patients, 62.7% were male, 72.9% were ≥30 years old, and 28.3% had a history of drug injection. Median CD4 was 132 cells/mm3, and 34.9% were clinical stage IV. Active cigarette smoking was reported by 36.3% with 14.0% smoking >10 cigarettes per day. Alcohol consumption was reported by 20.1% with 6.1% having ≥5 drinks per event. Overall 53.0% had a VL >100,000 cp/ml. Male gender, low body weight, low CD4 count, prior TB, and cigarette smoking were associated with high VL. Those who smoked 1–10 cigarettes per day were more likely to have high VL (aOR = 1.99, 95% CI = 1.15–3.45), while the smaller number of patients who smoked >10 cigarettes per day had a non-significant trend toward higher VL (aOR = 1.41, 95% CI = 0.75–2.66). Alcohol consumption was not significantly associated with high VL. Tobacco use is increasingly recognized as a contributor to premature morbidity and mortality among HIV-infected patients. In our study, cigarette smoking in the last 30 days was associated with a 1.5 to 2-fold higher odds of having an HIV VL >100,000 cp/ml among patients presenting for ART. These findings provide further evidence of the negative effects of tobacco use among HIV-infected patients.

Antiretroviral Treatment-Associated Hepatotoxicity and Anemia in Patients Receiving Stavudine or Zidovudine Containing Regimens in Sub- Saharan African Settings

Objective: Purpose of this study was to assess the prevalence and risk factors associated with development of hepatotoxicity and anemia following initiation of antiretroviral treatment (ART) containing stavudine (d4T) or zidovudine (AZT) in the first year of treatment in the African setting. Method: We evaluated aspartate aminotransferase and haemoglobin levels at baseline and at 1, 2, 3, 6, 9 and 12 months following ART initiation among 10,537 HIV-1 infected, ART-naive, non-pregnant adults in Mozambique and Malawi. The Cox proportional hazards model was used to assess risk factors for hepatotoxicity and anaemia in the first year following ART initiation. Results: The prevalence of ART-associated hepatotoxicity grades 1-2 declined in the first 3 months of ART from 13.5% to 10.8%, and grades 3-4 from 2.0% to 0.2% from month 1 to month 6. The prevalence of hepatotoxicity grades 1-2 peaked at month 6 due to the use of d4T (overall 14.2%; d4T-arm: 16.2%, AZT-arm: 5.8%). Anemia grades 1-2 and 3-4 declined from month 1 (13.3%, 3.2% respectively) to month 12 (3.0%, 0.5%, respectively). Risk factors for hepatotoxicity grades 1-2 included d4T use, an elevated VL pre-ART and female sex, and for anemia grade 1-2 and 3-4 AZT use, female sex and malaria. A high pre-ART VL was associated with the onset of severe anaemia. Not being malnourished was protective against mild hepatotoxicity and anemia. The ART-related mortality observed in the cohort was low (0.017%). Conclusion: In African settings the risk of untreated HIV outweighs the risk of anemia and hepatotoxicity mediated by ART. The prevalence of ART mediated hepatotoxicity declines in the first 3 to 6 months of treatment, and that of anemia declines in the first 12 months of ART. Patients with a poor health status at the start of ART are at highest risk of developing ART-associated hepatotoxicity and anemia.

PTU-111 A review of chronic hepatitis b virus infection in children in ireland

Introduction Although the majority of children with hepatitis B virus (HBV) infection remain asymptomatic, serious complications such as cirrhosis and hepatocellular carcinoma can occur in later life. Longterm follow up is important to identify these complications early. In Ireland, pregnant women are screened antenatally for HBV. Children born to HBV infected mothers are referred to the Rainbow Clinic. Method Data on all children with chronic HBV infection, attending the Rainbow Clinic from 2002 to 2014, were retrospectively reviewed using a standard data collection sheet. Chronic HBV infection is defined as HBsAg-positivity for greater than 6 months. Children with only one clinic visit or with HIV co-infection were excluded. Results 63 children with chronic HBV infection attended the Rainbow clinic between 2002 and 2014 (age range, 6 months-17 years).6 children were excluded (4 single clinic attendance; 2 HIV co-infection). 34 children (60%) were male. 13 children (23%) with chronic HBV were born in Ireland. The majority (44, 77%) were children immigrating to Ireland from overseas: Africa, 16; Central Asia, 14; Eastern Europe, 7; Unknown, 7. HBV was acquired vertically in 35 (61%) children and horizontally in 2. Parental HBV status was unknown in 22 children (15 adoptees).19 children had siblings with chronic HBV infection. 9 of 13 (69%) children born in Ireland received recommended prophylactic IVIG and HBV vaccine at birth. 4 (31%) received no prophylaxis. Birth details from children born outside of Ireland show suboptimal post natal prophylaxis in all: 13 of 16 received no prophylaxis and 3 received HBV vaccine alone. All 57 children had biochemistry performed twice a year. Abdominal ultrasound scans (USS) were performed in 49 children (86%).5 had abnormal USS (coarse echogenicity, 3; splenomegaly, 2). Liver biopsy was performed in 4 children with elevated ALT and high HBV VL. Biopsies showed fibrosis (3) or minimal inflammation (1). USS was normal in 3 of the 4 cases with abnormal biopsy. 3 children received antivirals (3TC) for fibrosis (2) and to reduce risk of transmission (1). Conclusion Immigration to Ireland accounts for the majority of paediatric HBV infection in this country. The majority of chronic HBV infection in children results from vertical transmission. Failure of postnatal prophylaxis remains a significant problem. Available evidence shows that 100% of foreign-born and 30% of Irish-born children with chronic HBV did not received recommended IVIG and vaccine prophylaxis. 4 children (7%) developed complications of chronic HBV. The need for improved diagnostic tools to identify children at risk of complicated HBV liver disease is again evidenced by failure of USS to identify those children with biopsy-proven abnormalities. Disclosure of interest None Declared.

High magnetic field studies of the vortex lattice structure inYBa2Cu3O7

We report on small angle neutron scattering measurements of the vortex lattice in twin-free YBa2Cu3O7, extending the previously investigated maximum field of 11~T up to 16.7~T with the field applied parallel to the c axis. This is the first microscopic study of vortex matter in this region of the superconducting phase. We find the high field VL displays a rhombic structure, with a field-dependent coordination that passes through a square configuration, and which does not lock-in to a field-independent structure. The VL pinning reduces with increasing temperature, but is seen to affect the VL correlation length even above the irreversibility temperature of the lattice structure. At high field and temperature we observe a melting transition, which appears to be first order, with no detectable signal from a vortex liquid above the transition.

Human resource assessment for scaling up VL active case detection in Bangladesh, India and Nepal

To determine whether medical staff at PHC level would have the time to take up additional activities such as 1-day fever camps for active VL case detection. This article assessed the workload of health staff of different professional categories working at health facilities in Bangladesh, India and Nepal. Data were collected from different sites in high endemic VL areas. The study population was the health staff of government health facilities at all levels. Workload indicators of staffing need (WISN) software were adopted to carry out the analysis of staff workload and their availability in the selected health facility. The WISN difference and WISN ratio for a particular health facility were calculated from actual staffing available and calculated staffing requirement. The results showed a mixed picture of the availability of health workers. In most settings of Bangladesh and India, physicians with or without laboratory technicians would have time for active case detection. In Nepal, this would be performed by trained nurses and paramedical personnel. If all vacant posts were filled, active case detection could be performed more easily. The elimination programme can be scaled up with the current staffing levels in the endemic areas with some short training if and when necessary.