Viral load monitoring for people living with HIV in the era of test and treat: progress made and challenges ahead - a systematic review.

BACKGROUND: In 2016, we conducted a systematic review to assess the feasibility of treatment monitoring for people living with HIV (PLHIV) receiving antiretroviral therapy (ART) in low and middle-income countries (LMICs), in line with the 90-90-90 treatment target. By 2020, global estimates suggest the 90-90-90 target, particularly the last 90, remains unattainable in many LMICs. This study aims to review the progress and identify needs for public health interventions to improve viral load monitoring and viral suppression for PLHIV in LMICs. METHODS: A literature search was conducted using an update of the initial search strategy developed for the 2016 review. Electronic databases (Medline and PubMed) were searched to identify relevant literature published in English between Dec 2015 and August 2021. The primary outcome was initial viral load (VL) monitoring (the proportion of PLHIV on ART and eligible for VL monitoring who received a VL test). Secondary outcomes included follow-up VL monitoring (the proportion of PLHIV who received a follow-up VL after an initial elevated VL test), confirmation of treatment failure (the proportion of PLHIV who had two consecutive elevated VL results) and switching treatment regimen rates (the proportion of PLHIV who switched treatment regimen after confirmation of treatment failure). RESULTS: The search strategy identified 1984 non-duplicate records, of which 34 studies were included in the review. Marked variations in initial VL monitoring coverage were reported across study settings/countries (range: 12-93% median: 74% IQR: 46-82%) and study populations (adults (range: 25-96%, median: 67% IQR: 50-84%), children, adolescents/young people (range: 2-94%, median: 72% IQR: 47-85%), and pregnant women (range: 32-82%, median: 57% IQR: 43-71%)). Community-based models reported higher VL monitoring (median: 85%, IQR: 82-88%) compared to decentralised care at primary health facility (median: 64%, IRQ: 48-82%). Suboptimal uptake of follow-up VL monitoring and low regimen switching rates were observed. CONCLUSIONS: Substantial gaps in VL coverage across study settings and study populations were evident, with limited data availability outside of sub-Saharan Africa. Further research is needed to fill the data gaps. Development and implementation of innovative, community-based interventions are required to improve VL monitoring and address the "failure cascade" in PLHIV on ART who fail to achieve viral suppression.

Elevated Intracranial Pressure Associated With Exogenous Hormonal Therapy Used for Gender Affirmation.

BACKGROUND: Addison disease, corticosteroid withdrawal, and taking synthetic growth hormone have been linked with development of intracranial hypertension, but there is still debate on whether administration of other exogenous hormones plays a role in precipitating elevated pressure. The growing use of hormonal therapy for gender affirmation provides an opportunity to explore this possibility. METHODS: All transgender patients taking exogenous hormones for female-to-male (FTM) and male-to-female (MTF) transitions who were diagnosed with intracranial hypertension at Massachusetts Eye and Ear Infirmary, Massachusetts General Hospital and Beth Israel Deaconess Medical Center between August 2014 and November 2018 were included in a retrospective review. Visual acuity, type, and dose of exogenous hormone, visual field testing, clinical exam, results of neuroimaging and lumbar puncture, and treatment modalities were catalogued and analyzed. RESULTS: Six transgender individuals were identified. Five were FTM, with an average hormone treatment time of 18.4 months, and one was MTF who had been treated with hormones for 4 years. The average age of all patients was 23.5 years. The average time between onset of symptoms and presentation was 5 months. Fifty percent of the patients reported pulse-synchronous tinnitus, 83% reported positional headache, 33% reported transient visual obscurations, and 16% reported diplopia. Lumbar punctures performed on 4 of the patients revealed elevated opening pressures and normal cerebrospinal fluid constituents. MRI findings consistent with elevated intracranial pressure (ICP) were present in the other 2 patients in whom lumbar puncture was unsuccessful. Four patients were treated with acetazolamide and one was treated with topiramate, with an average follow-up time of 15.7 months. All patients demonstrated bilateral optic disc swelling, and all maintained normal acuity and color vision. Performance on visual field testing was not significantly affected in any patient. CONCLUSIONS: This is the largest reported series to date of gender-transitioning patients with intracranial hypertension, including one novel MTF conversion. These observations warrant further investigation into the possible link of exogenous hormonal therapy and elevated ICP and any mechanisms or confounders underlying this potential association.

Effect of Regiochemistry and Methylation on the Anticancer Activity of a Ferrocene-Containing Organometallic Nucleoside Analogue.

Four new bis-substituted ferrocene derivatives containing either a hydroxyalkyl or methoxyalkyl group and either a thyminyl or methylthyminyl group have been synthesised and characterised by a range of spectroscopic and analytical techniques. They were included in a structure-activity-relationship (SAR) study probing anticancer activities in osteosarcoma (bone cancer) cell lines and were compared with a known lead compound, 1-(S,Rp ), a nucleoside analogue that is highly toxic to cancer cells. Biological studies using the MTT assay revealed that a regioisomer of ferronucleoside 1-(S,Rp ), which only differs from the lead compound in being substituted on two cyclopentadienyl rings rather than one, was over 20 times less cytotoxic. On the other hand, methylated derivatives of 1-(S,Rp ) showed comparable cytotoxicities to the lead compound. Overall these studies indicate that a mechanism of action for 1-(S,Rp ) cannot proceed through alcohol phosphorylation and that its geometry and size, rather than any particular functional group, are crucial factors in explaining its high anticancer activity.

Validation of genome-wide association study (GWAS)-identified disease risk alleles with patient-specific stem cell lines.

While the past decade has seen great progress in mapping loci for common diseases, studying how these risk alleles lead to pathology remains a challenge. Age-related macular degeneration (AMD) affects 9 million older Americans, and is characterized by the loss of the retinal pigment epithelium (RPE). Although the closely linked genome-wide association studies ARMS2/HTRA1 genes, located at the chromosome 10q26 locus, are strongly associated with the risk of AMD, their downstream targets are unknown. Low population frequencies of risk alleles in tissue banks make it impractical to study their function in cells derived from autopsied tissue. Moreover, autopsy eyes from end-stage AMD patients, where age-related RPE atrophy and fibrosis are already present, cannot be used to determine how abnormal ARMS2/HTRA1 expression can initiate RPE pathology. Instead, induced pluripotent stem (iPS) cell-derived RPE from patients provides us with earlier stage AMD patient-specific cells and allows us to analyze the underlying mechanisms at this critical time point. An unbiased proteome screen of A2E-aged patient-specific iPS-derived RPE cell lines identified superoxide dismutase 2 (SOD2)-mediated antioxidative defense in the genetic allele's susceptibility of AMD. The AMD-associated risk haplotype (T-in/del-A) impairs the ability of the RPE to defend against aging-related oxidative stress. SOD2 defense is impaired in RPE homozygous for the risk haplotype (T-in/del-A; T-in/del-A), while the effect was less pronounced in RPE homozygous for the protective haplotype (G-Wt-G; G-Wt-G). ARMS2/HTRA1 risk alleles decrease SOD2 defense, making RPE more susceptible to oxidative damage and thereby contributing to AMD pathogenesis.

Cobalt-Chromium Metallosis With Normal Electroretinogram.

BACKGROUND: Ocular cobalt toxicity is a rare phenomenon reported with increased frequency due to the rise of cobalt-chromium metal hip implants. We report the case of a 66-year-old previously healthy man who developed decreased vision due to cobalt-chromium toxicity from a metal-on-metal hip arthroplasty. Our objective was to determine whether the origin of his visual loss was due to toxicity of the optic nerve, of the retina, or of both. METHODS: Ocular examination, 10-2 SITA-Standard Humphrey Visual Field (VF), standard full-field electroretinogram (ERG) as indicated by the International Society for Clinical Electrophysiology of Vision (ISCEV), multifocal electroretinogram (mfERG), multifocal visual evoked potentials (mfVEP), and optical coherence tomography (OCT) were conducted. RESULTS: Ocular examination revealed decreased visual acuity, poor color vision, normal funduscopy, and cecocentral scotomas on VF testing. Because his right eye was amblyopic since childhood, test results from only the left eye are shown. Electrophysiology studies revealed an ISCEV standard full-field ERG with photopic and scotopic responses within normal limits, mfERG with amplitudes and latencies within normal limits, and mfVEP with latencies within normal limits, but with decreased central amplitudes. Peripapillary and macular OCT showed retinal nerve fiber layer and retinal ganglion cell-inner plexiform layer thickness within normal limits. CONCLUSION: Because decreased color vision and cecocentral scotoma on 10-2 VF are most consistent with toxic optic neuropathy, and decreased central amplitudes on mfVEP are suggestive of neural dysfunction, we hypothesize that our patient presented with an early stage of optic nerve toxicity that was not yet apparent as a structural abnormality on OCT.

Personalized Medicine: Cell and Gene Therapy Based on Patient-Specific iPSC-Derived Retinal Pigment Epithelium Cells.

Interest in generating human induced pluripotent stem (iPS) cells for stem cell modeling of diseases has overtaken that of patient-specific human embryonic stem cells due to the ethical, technical, and political concerns associated with the latter. In ophthalmology, researchers are currently using iPS cells to explore various applications, including: (1) modeling of retinal diseases using patient-specific iPS cells; (2) autologous transplantation of differentiated retinal cells that undergo gene correction at the iPS cell stage via gene editing tools (e.g., CRISPR/Cas9, TALENs and ZFNs); and (3) autologous transplantation of patient-specific iPS-derived retinal cells treated with gene therapy. In this review, we will discuss the uses of patient-specific iPS cells for differentiating into retinal pigment epithelium (RPE) cells, uncovering disease pathophysiology, and developing new treatments such as gene therapy and cell replacement therapy via autologous transplantation.

Design, synthesis, and in vivo activity of novel inhibitors of delta-5 desaturase for the treatment of metabolic syndrome.

The synthesis, SAR, and in vivo activity of inhibitors of delta-5 desaturase are described. Ring-constraint of the initial series provided access to a variety of in vitro active chemotypes, from which the indazole was selected. Examples from the indazole series displayed in vivo activity in reducing the enzymatic activity of liver delta-5 desaturase.

Gene therapy in patient-specific stem cell lines and a preclinical model of retinitis pigmentosa with membrane frizzled-related protein defects.

Defects in Membrane Frizzled-related Protein (MFRP) cause autosomal recessive retinitis pigmentosa (RP). MFRP codes for a retinal pigment epithelium (RPE)-specific membrane receptor of unknown function. In patient-specific induced pluripotent stem (iPS)-derived RPE cells, precise levels of MFRP, and its dicistronic partner CTRP5, are critical to the regulation of actin organization. Overexpression of CTRP5 in naïve human RPE cells phenocopied behavior of MFRP-deficient patient RPE (iPS-RPE) cells. AAV8 (Y733F) vector expressing human MFRP rescued the actin disorganization phenotype and restored apical microvilli in patient-specific iPS-RPE cell lines. As a result, AAV-treated MFRP mutant iPS-RPE recovered pigmentation and transepithelial resistance. The efficacy of AAV-mediated gene therapy was also evaluated in Mfrp(rd6)/Mfrp(rd6) mice--an established preclinical model of RP--and long-term improvement in visual function was observed in AAV-Mfrp-treated mice. This report is the first to indicate the successful use of human iPS-RPE cells as a recipient for gene therapy. The observed favorable response to gene therapy in both patient-specific cell lines, and the Mfrp(rd6)/Mfrp(rd6) preclinical model suggests that this form of degeneration caused by MFRP mutations is a potential target for interventional trials.

Knowledge of HIV and factors associated with attitudes towards HIV among final-year medical students at Hanoi medical university in Vietnam.

BACKGROUND: The success of HIV care strongly depends upon skills of the healthcare worker. Vietnam has a punitive history towards HIV and even though this has changed recently, persons living with HIV are still facing discrimination. The objective of this paper is to assess the gaps in knowledge of HIV and factors associated with discriminatory attitudes towards persons living with HIV among medical students in order to improve medical training. METHODS: In a cross-sectional quantitative study using a structured questionnaire, 200 final-year medical students at Hanoi Medical University were approached for data collection in May of 2012. Descriptive statistics (percentages) were used to present four HIV knowledge tests. Linear regression models were examined to highlight factors that are associated with general attitudes towards HIV and attitudes towards HIV in a clinical setting. RESULTS: Although students performed overall well in the knowledge category of HIV discrimination and stigma, there were several gaps in knowledge of HIV, including the categories of HIV-related basic sciences, prevention, and care and treatment. Knowledge of stigma and discrimination was a significant positive predictor of General non-prejudicial attitude to HIV and AIDS (ß=0.186, P<0.01) and Non-discriminatory attitude to HIV and AIDS at work (ß=0.188, P<0.01). Training on methadone treatment was found to be a significant positive predictor (ß=0.168, P<0.05) while family size was negatively associated (ß=-0.170, P<0.05) with General non-prejudicial attitude to HIV and AIDS. CONCLUSIONS: The study suggests a need for incorporating HIV training into the core curricula for medical students. As persons who inject drugs carry a proportionately high burden of HIV in Vietnam, it is also important to include methadone training for students.

Crosstalk between genomic variants and DNA methylation in FLT3 mutant acute myeloid leukemia.

Acute myeloid leukemia (AML) is a type of blood cancer with diverse genetic variations and DNA methylation alterations. By studying the interaction of gene mutations, expression, and DNA methylation, we aimed to gain valuable insights into the processes that lead to block differentiation in AML. We analyzed TCGA-LAML data (173 samples) with RNA sequencing and DNA methylation arrays, comparing FLT3 mutant (48) and wild-type (125) cases. We conducted differential gene expression analysis using cBioPortal, identified DNA methylation differences with ChAMP tool, and correlated them with gene expression changes. Gene set enrichment analysis (g:Profiler) revealed significant biological processes and pathways. ShinyGo and GeneCards were used to find potential transcription factors and their binding sites among significant genes. We found significant differentially expressed genes (DEGs) negatively correlated with their most significant methylation probes (Pearson correlation coefficient of -0.49, P-value <0.001) between FLT3 mutant and wild-type groups. Moreover, our exploration of 450 k CpG sites uncovered a global hypo-methylated status in 168 DEGs. Notably, these methylation changes were enriched in the promoter regions of Homebox superfamily gene, which are crucial in transcriptional-regulating pathways in blood cancer. Furthermore, in FLT3 mutant AML patient samples, we observed overexpress of WT1, a transcription factor known to bind homeobox gene family. This finding suggests a potential mechanism by which WT1 recruits TET2 to demethylate specific genomic regions. Integrating gene expression and DNA methylation analyses shed light on the impact of FLT3 mutations on cancer cell development and differentiation, supporting a two-hit model in AML. This research advances understanding of AML and fosters targeted therapeutic strategy development.

Predictors of Free Sugars Intake Trajectories across Early Childhood-Results from the SMILE Birth Cohort Study.

Foods and beverages high in free sugars can displace healthier choices and increase the risk of weight gain, dental caries, and noncommunicable diseases. Little is known about the intake of free sugars across early childhood. This study aimed to examine the longitudinal intake from 1 to 5 years of free sugars and identify the independent maternal and child-related predictors of intake in a cohort of Australian children participating in the Study of Mothers' and Infants' Life Events Affecting Oral Health (SMILE). Free sugars intake (FSI) was previously estimated at 1, 2, and 5 years of age, and three distinct FSI trajectories were determined using group-based trajectory modelling analysis. This study utilized multinomial logistic regression to identify the maternal and child-related predictors of the trajectories. The risk of following the 'high and increasing' trajectory of FSI compared to the 'low and fast increasing' trajectory was inversely associated with socio-economic disadvantage (aRRR 0.83; 95% CI 0.75-0.92; p < 0.001), lower for females (aRRR 0.56; 95% CI 0.32-0.98; p = 0.042), and higher in children with two or more older siblings at birth (aRRR 2.32; 95% CI 0.99-5.42; p = 0.052). Differences in trajectories of FSI were evident from an early age and a high trajectory of FSI was associated primarily with socio-economic disadvantage, providing another example of diet quality following a social gradient.

Trajectories of child free sugars intake and dental caries - a population-based birth cohort study.

OBJECTIVES: To investigate the association between trajectories of free sugars intake during the first five years of life and dental caries experience at five years. METHODS: Data from the SMILE population-based prospective birth cohort study, collected at one, two and five years old, were used. A 3-days dietary diary and food frequency questionnaire were used to estimate free sugars intake (FSI) in grams. The primary outcomes were dental caries prevalence and experience (dmfs). The Group-Based Trajectory Modelling method was used to characterize three FSI trajectories ('Low and increasing'; 'Moderate and increasing'; and 'High and increasing'), which were the main exposures. Multivariable regression models were generated to compute adjusted prevalence ratios (APR) and rate ratios (ARR) for the exposure, controlling for socioeconomic factors. RESULTS: The prevalence of caries was 23.3%, with a mean dmfs of 1.4, and a median of 3.0 among those who had caries. There were clear gradients of caries prevalence and experience by the FSI trajectories. The 'High and increasing' had an APR of 2.13 (95%CI 1.23-3.70) and ARR of 2.77 (95%CI 1.45-5.32) against the 'Low and increasing'. The 'Moderate and increasing' group had intermediate estimates. A quarter of the caries cases could have been prevented if the whole study sample had been in the 'Low and increasing' FSI trajectory. CONCLUSION: A sustained, high trajectory of FSI from a young age was positively associated with child dental caries. Measures to minimise consumption of free sugars must commence early in life. CLINICAL SIGNIFICANCE: The study has provided high level evidence to inform clinicians' decisions in promoting a healthy dietary pattern for young children.

The effect of participatory community communication on HIV preventive behaviors among ethnic minority youth in central Vietnam.

BACKGROUND: In Vietnam, socially marginalized groups such as ethnic minorities in mountainous areas are often difficult to engage in HIV research and prevention programs. This intervention study aimed to estimate the effect of participatory community communication (PCC) on changing HIV preventive ideation and behavior among ethnic minority youth in a rural district from central Vietnam. METHODS: In a cross-sectional survey after the PCC intervention, using a structured questionnaire, 800 ethnic minority youth were approached for face-to-face interviews. Propensity score matching (PSM) technique was then utilized to match these participants into two groups-intervention and control-for estimating the effect of the PCC. RESULTS: HIV preventive knowledge and ideation tended to increase as the level of recall changed accordingly. The campaign had a significant indirect effect on condom use through its effect on ideation or perceptions. When intervention and control group statistically equivalently reached in terms of individual and social characteristics by PSM, proportions of displaying HIV preventive knowledge, ideation and condom use were significantly higher in intervention group than in matched control counterparts, accounting for net differences of 7.4%, 12.7% and 5%, respectively, and can be translated into the number of 210; 361 and 142 ethnic minority youth in the population. CONCLUSIONS: The study informs public health implications both theoretically and practically to guide effective HIV control programs for marginalized communities in resources-constrained settings like rural Vietnam and similar contexts of developing countries.

Ocular adverse events following intravitreal brolucizumab for neovascular age-related macular degeneration at a single tertiary care center.

PURPOSE: To determine the incidence of ocular adverse effects (AEs) following brolucizumab injection for neovascular age-related macular degeneration at a tertiary academic institution. DESIGN: Retrospective, single center cohort study. PARTICIPANTS: All patients who received an intravitreal injection of brolucizumab 6 mg for neovascular age-related macular degeneration between October 7, 2019 and July 31, 2020. METHODS: Medical records of all patients who received brolucizumab 6 mg during the aforementioned time period were carefully reviewed and all ocular adverse effects after injection were charted. MAIN OUTCOME MEASURES: Incidence of post-injection ocular AEs, including intraocular inflammation (IOI), and time to development of AEs after injection. RESULTS: A total of 77 patients received brolucizumab 6 mg for a total of 115 administrations during the study period. There were 4 AEs (3.5%), including three cases of IOI (2.6%), one central retinal artery occlusion, and one retinal detachment. Two men and two women were affected. CONCLUSION: Ocular AEs, including those leading to severe vision loss, may develop after intravitreal brolucizumab 6 mg. A careful discussion of benefits and risks to brolucizumab should be conducted with all patients. PRECIS: In this first case series of ocular adverse effects after brolucizumab 6 mg injection at a single tertiary care center, the incidence of ocular adverse effects was 3.5%, including a 2.6% incidence of intraocular inflammation.

Progress toward HIV elimination goals: trends in and projections of annual HIV testing and condom use in Africa.

OBJECTIVES: To estimate trends in and projections of annual HIV testing and condom use at last higher-risk sex and to calculate the probability of reaching key United Nations Programme on AIDS (UNAIDS)'s target. DESIGN: We included 114 nationally-representative datasets in 38 African countries from Demographic and Health Surveys and Multiple Indicator Cluster Surveys with 1 456 224 sexually active adults age 15-49 from 2003 to 2018. METHODS: We applied Bayesian mixed effect models to estimate the coverage of annual HIV testing and condom use at last higher-risk sex for every country and year to 2030 and the probability of reaching UNAIDS testing and condom use targets of 95% coverage by 2030. RESULTS: Seven countries saw downward trends in annual HIV testing and four saw decreases in condom use at higher-risk sex, whereas most countries have upward trends in both indicators. The highest coverage of testing in 2030 is predicted in Swaziland with 92.6% (95% credible interval: 74.5-98.1%), Uganda with 90.5% (72.2-97.2%), and Lesotho with 90.5% (69.4%-97.6%). Meanwhile, Swaziland, Lesotho, and Namibia will have the highest proportion of condom use in 2030 at 85.0% (57.8-96.1%), 75.6% (42.3-93.6%), and 75.5% (42.4-93.2%). The probabilities of reaching targets were very low for both HIV testing (0-28.5%) and condom use (0-12.1%). CONCLUSIONS: We observed limited progress on annual HIV testing and condom use at last higher-risk sex in Africa and little prospect of reaching global targets for HIV/AIDS elimination. Although some funding agencies are considering withdrawal from supporting Africa, more attention to funding and expanding testing and treatment is needed in this region.

Assessing the Uniformity of Uveitis Clinical Concepts and Associated ICD-10 Codes Across Health Care Systems Sharing the Same Electronic Health Records System.

IMPORTANCE: Big data studies may allow for the aggregation of patients with rare diseases such as uveitis to answer important clinical questions. Standardization of uveitis-related variables will be necessary, including the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes used to identify patients of interest. There are currently limited data on the uniformity of diagnosis mapping to ICD-10 codes for uveitis diagnoses among different health systems. OBJECTIVE: To assess the degree of uniformity in mapping of uveitis clinical concepts to ICD-10 codes across health care systems using the same electronic health record (EHR) system. DESIGN, SETTING, AND PARTICIPANTS: This multicenter survey study was conducted between September 14 and October 9, 2020, at 5 academic health care systems that use the Epic EHR. Researchers from the University of Washington, Harvard University, Stanford University, Yale University, and the University of California, San Francisco queried 54 uveitis-related diagnostic terms and recorded the associated ICD-10 codes. MAIN OUTCOMES AND MEASURES: The degree of uniformity for uveitis clinical concepts and associated ICD-10 codes. RESULTS: Fifty-four uveitis-related diagnostic terms were queried within the Epic EHR at 5 different health care systems. There was perfect agreement among all 5 centers for 52 of the 54 diagnostic terms. Two diagnostic terms had differences in ICD-10 coding: juvenile idiopathic arthritis associated chronic uveitis and intermediate uveitis. Intermediate uveitis was associated with codes H20.1x (ICD-10 description: chronic iridocyclitis) or H20.9 (ICD-10 description: unspecified iridocyclitis) in 3 centers while being associated with code H30.2x (ICD-10 description: posterior cyclitis) at the 2 remaining centers. The discrepancies appear to be related to a recent update in diagnostic mapping in the Epic EHR. CONCLUSIONS AND RELEVANCE: This study suggests that ICD-10 code mapping to uveitis diagnostic terminology appears to be highly uniform at different centers with the Epic EHR. However, temporal changes in diagnosis mapping to ICD-10 codes and a lack of 1-to-1 mapping of diagnosis to ICD-10 code add additional sources of complexity to the interpretation of big data studies in uveitis.

Adherence to highly active antiretroviral therapy among people living with HIV and associated high-risk behaviours and clinical characteristics: A cross-sectional survey in Vietnam.

Although Vietnam has promoted the utilisation of highly active antiretroviral therapy (HAART) towards HIV elimination targets, adherence to treatment has remained under-investigated. We aimed to describe high-risk behaviours and clinical characteristics by adherence status and to identify the factors associated with non-adherence. We included 426 people living with HIV (PLWH) currently or previously involved in HAART. Most participants were men (75.4%), young (33.6 years), with low income and low education levels. Non-adherent PLWH (11.5%) were more likely to have a larger number of sex partners (p-value = 0.053), sex without condom use (p-value = 0.007) and not receive result at hospital or voluntary test centre (p-value = 0.001). Multiple logistic regression analysis showed that demographic (education levels), sexual risk behaviours (multiple sex partners and sex without using condom) and clinical characteristics (time and facility at first time received HIV-positive result) were associated with HAART non-adherence. There are differences in associated factors between women (education levels and place of HIV testing) and men (multiple sex partners). Gender-specific programs, changing risky behaviours and reducing harms among PLWH may benefit adherence. We highlight the need to improve the quantity and quality of HIV/AIDS services in Vietnam, especially in pre- and post-test counselling, to achieve better HAART adherence, working towards ending AIDS in 2030.

Complete RPE and outer retinal atrophy in patients receiving anti-VEGF treatment for neovascular age-related macular degeneration.

IMPORTANCE: Neovascular age-related macular degeneration (nAMD) is a leading cause of blindness with several intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents available for its management such as aflibercept, bevacizumab, and ranibizumab. However, direct comparisons between these three agents among the same patient population are limited. OBJECTIVE: To assess the rate and growth of complete retinal pigment epithelium and outer retinal atrophy (cRORA) in eyes with nAMD treated with aflibercept, bevacizumab, and/or ranibizumab. METHOD: Retrospective cohort study of patients with treatment-naïve neovascular AMD seen at an academic hospital between October 2006 and February 2019. Study eyes were treated with intravitreal injections of aflibercept, bevacizumab, and/or ranibizumab and followed for two years. MAIN OUTCOMES AND MEASURES: cRORA prevalence, location, size, and growth rate. Eyes were imaged with Cirrus spectral domain optical coherence tomography (SD-OCT). Presence and size of cRORA were calculated using the FDA-approved Advanced RPE Analysis software. Linear regression models were used to correlate cRORA progression with baseline demographic and ocular characteristics, anti-VEGF drug, and number of injections. Unpaired t-tests, ANOVA, and linear regression models were computed with SAS 9.4. RESULTS: 197 eyes from 158 patients (mean age 78.9, 62.9% women) received an average of 13 anti-VEGF injections over 24 months. 22% developed new cRORA. Mean cRORA area increased from 1.71 mm2 to 2.93 mm2. At 24 months, eyes with 11+ injections had significantly less cRORA area (11+ injections, 4.02 mm2; ≤ 10 injections, 2.46 mm2; p = 0.01) and growth rate (11+ injections, 0.41 mm2/year; ≤ 10 injections, 1.05 mm2/year; p = 0.02). Choice of anti-VEGF drug yielded no significant difference in cRORA progression. CONCLUSIONS AND RELEVANCE: Treating nAMD with aflibercept, bevacizumab or ranibizumab demonstrated comparable cRORA development at 24 months. Number of injections inversely correlated with cRORA area and growth. These results warrant further investigation in the pathophysiology of cRORA in anti-VEGF treated eyes.

Organometallic nucleoside analogues: effect of the metallocene metal atom on cancer cell line toxicity.

A new chiral organometallic nucleoside analogue containing ruthenocene is reported, in which alkylthymine and alkylhydroxyl groups are attached in adjacent positions on one cyclopentadienyl ring. The synthetic procedures for this metallocene derivative and two control compounds are described, along with their characterisation by cyclic voltammetry and X-ray crystallography. Their biological activities in a human pancreatic cancer cell line (MIA-Pa-Ca-2) were significantly lower than those of three previously reported analogous ferrocene compounds, indicating that the choice of metallocene metal atom (Fe or Ru) plays a pivotal role in determining the anticancer properties of these nucleoside analogues, which in turn suggests a different mode of action from that of a conventional nucleoside analogue.