Changes in atherosclerotic cardiovascular disease risk over time among people living with HIV.

OBJECTIVE: To describe changes in atherosclerotic cardiovascular disease (ASCVD) risk over time among people living with HIV (PLHIV). METHODS: We used data from the TREAT Asia HIV Observational Database (TAHOD) and the Australian HIV Observational Database (AHOD). Five-year ASCVD risk was calculated using the D:A:D equation. Individuals were eligible for inclusion if they were aged ≥18 years, had started ART, had no previous history of ASCVD and had complete ASCVD risk factor data available within the first 5 years of ART initiation. RESULTS: A total of 3368 adults contributed data, 3221 were from TAHOD and 147 were from AHOD. The median age at ART initiation was 36 [IQR 31-43] years for TAHOD participants, and 42 [IQR 35-50] years for AHOD participants. Most TAHOD (70.4%) and AHOD (91.8%) participants were male. Overall, ASCVD risk increased from 0.84% (95% CI 0.81%-0.87%) at ART initiation to 1.34% (95% CI 1.29%-1.39%) after 5 years on ART. After adjusting for traditional and HIV-associated ASCVD risk factors, ASCVD risk increased at a similar rate among sub-populations defined by HIV exposure (heterosexuals, men who have sex with men, people who inject drugs), race/ethnicity (Caucasian and Asian) and nadir CD4 at ART initiation (<200 and ≥200 cells/mm3). CONCLUSIONS: These findings emphasize the growing burden of ASCVD risk among PLHIV and the need to develop interventions that are effective across a broad range of HIV sub-populations.

Unnecessary antibiotic use in men who have sex with men (MSM) with anogenital symptoms attending a sexual health clinic: a retrospective analysis.

OBJECTIVES: To quantify the amount of unnecessary antibiotics, in particular ceftriaxone, given to men who have sex with men (MSM) with anogenital symptoms as part of presumptive management in an urban sexual health clinic and examine factors associated with unnecessary ceftriaxone. METHODS: This is a retrospective cross-sectional analysis of electronic records from all visits involving MSM reporting symptoms of bacterial sexually transmitted infection (STI) and who received presumptive antibiotics at Sydney Sexual Health Centre. The following variables were extracted: demographic and sexual behaviour data, presenting symptoms, prior STI diagnoses, use of anoscopy, use of point-of-care microscopy, prescriptions of antibiotics and subsequent nucleic acid amplification testing (NAAT) results for chlamydia and gonorrhoea in all anatomical sites (urethra, pharynx and rectum). We defined unnecessary antibiotic as an agent prescribed to treat an STI organism that was subsequently not detected. RESULTS: Among 1061 visits in this analysis, 41.8% yielded negative NAAT results for both chlamydia and gonorrhoea in all anatomical sites. There were 44.3% of visits which had positive gonorrhoea NAAT result in at least one anatomical site. There were 187 courses of ceftriaxone prescribed in patients who tested negative for gonorrhoea in all anatomical sites and therefore were unnecessary. Unnecessary ceftriaxone prescribing occurred in 50.2% of visits with anorectal symptoms, 19.6% of scrotal symptoms and 7.3% of urethral symptoms. Microscopy was associated with significantly less unnecessary ceftriaxone in urethral but not anorectal or scrotal presentations. In multivariable analysis, the following factors were associated with a higher likelihood of unnecessary ceftriaxone use: anorectal symptoms, scrotal symptoms, gonorrhoea in the preceding year, contact of a bacterial STI and living with HIV. CONCLUSIONS: This study highlights the significant amount of unnecessary ceftriaxone used for STI symptoms in MSM. A new pathway incorporating rapid point-of-care molecular testing in symptomatic patients may improve the precision of antibiotic prescribing and reduce unnecessary use.

Projected impact of population aging on non-communicable disease burden and costs in the Kingdom of Saudi Arabia, 2020-2030.

BACKGROUND: The number of people aged greater than 65 years per 100 people aged 20-64 years is expected to almost double in The Kingdom of Saudi Arabia (KSA) between 2020 and 2030. We therefore aimed to quantify the growing non-communicable disease (NCD) burden in KSA between 2020 and 2030, and the impact this will have on the national health budget. METHODS: Ten priority NCDs were selected: ischemic heart disease, stroke, type 2 diabetes, chronic obstructive pulmonary disease, chronic kidney disease, dementia, depression, osteoarthritis, colorectal cancer, and breast cancer. Age- and sex-specific prevalence was projected for each priority NCD between 2020 and 2030. Treatment coverage rates were applied to the projected prevalence estimates to calculate the number of patients incurring treatment costs for each condition. For each priority NCD, the average cost-of-illness was estimated based on published literature. The impact of changes to our base-case model in terms of assumed disease prevalence, treatment coverage, and costs of care, coming into effect from 2023 onwards, were explored. RESULTS: The prevalence estimates for colorectal cancer and stroke were estimated to almost double between 2020 and 2030 (97% and 88% increase, respectively). The only priority NCD prevalence projected to increase by less than 60% between 2020 and 2030 was for depression (22% increase). It is estimated that the total cost of managing priority NCDs in KSA will increase from USD 19.8 billion in 2020 to USD 32.4 billion in 2030 (an increase of USD 12.6 billion or 63%). The largest USD value increases were projected for osteoarthritis (USD 4.3 billion), diabetes (USD 2.4 billion), and dementia (USD 1.9 billion). In scenario analyses, our 2030 projection for the total cost of managing priority NCDs varied between USD 29.2 billion - USD 35.7 billion. CONCLUSIONS: Managing the growing NCD burden in KSA's aging population will require substantial healthcare spending increases over the coming years.

Weight change with integrase strand transfer inhibitors among virally suppressed Thai people living with HIV.

BACKGROUND: We compared weight changes in virally suppressed people living with HIV (PLWH) switching to integrase strand transfer inhibitors (INSTIs) with those remaining on an INSTI or non-INSTI regimen. METHODS: PLWH aged ≥18 years with weight measurements available at baseline between 2001 and 2020 were included. Viral suppression was defined as having had a viral load <400 copies/mL for 6 months. Baseline was defined as the time of switching from a non-INSTI to an INSTI regimen whilst virally suppressed (switch group) or the time that viral suppression was achieved (remain groups). Generalized estimating equations adjusted for age, sex and baseline weight were used to model weight changes 6, 12, 18 and 24 months after baseline. RESULTS: A total of 1673 PLWH contributed 1952 episodes of viral suppression-143 (7.3%) episodes were among PLWH who had switched from a non-INSTI to an INSTI, 102 (5.2%) episodes were among PLWH who remained on an INSTI and 1707 (87.4%) episodes were among PLWH who remained on a non-INSTI. PLWH in the switch group had significantly greater weight gain than those in the remain groups at 6, 12 and 18 months after achieving viral suppression. By 24 months, weight change on all regimens started to converge. Tenofovir alafenamide use was not significantly associated with weight gain in adjusted models. CONCLUSIONS: Our findings suggest that the mechanisms of weight gain due to INSTI use go beyond their superior efficacy over other antiretrovirals in controlling HIV or the effect of the 'return-to-health' phenomenon. Further research is needed to understand the mechanisms of such weight gain.

Physical function limitation among gay and bisexual men aged ≥55years with and without HIV: findings from the Australian Positive and Peers Longevity Evaluation Study (APPLES).

BACKGROUND: As people living with HIV now have a life expectancy approaching that of the general population, clinical care focuses increasingly on the management and prevention of comorbidities and conditions associated with aging. We aimed to assess the prevalence of physical function (PF) limitation among gay and bisexual men (GBM) and determine whether HIV is associated with severe PF limitation in this population. METHODS: We analysed cross-sectional data from GBM aged ≥55years in the Australian Positive and Peers Longevity Evaluation Study who completed a self-administered survey on health and lifestyle factors. PF was measured using the Medical Outcomes Study-Physical Functioning scale. Factors associated with severe PF limitation were assessed using logistic regression. RESULTS: The survey was completed by 381 men: 186 without HIV and 195 with HIV. Median age was 64.3years for GBM without HIV and 62.1years for GBM with HIV. Compared with men without HIV, those with HIV had higher proportions of severe (13.3% vs 8.1%) and moderate-to-severe (26.7% vs 24.2%) PF limitation. Severe PF limitation commonly involved difficulty with vigorous activity (95% with severe PF limitation described being limited a lot), climbing several flights of stairs (68.4% limited a lot), bending, kneeling or stooping (60.5% limited a lot), and walking 1km (55.0% limited a lot). In a model adjusted for age, body mass index, typical duration of physical activity, psychological distress, and number of comorbidities, we found a significant association between HIV and severe PF limitation (adjusted odds ratio 3.3 vs not having HIV, 95% confidence interval 1.3-8.7). CONCLUSIONS: The biological mechanisms underlying this association require further investigation, particularly given the growing age of the HIV population and inevitable increase in the burden of PF limitation.

ß1D integrin splice variant stabilizes integrin dynamics and reduces integrin signaling by limiting paxillin recruitment.

Heterodimeric integrin receptors control cell adhesion, migration and extracellular matrix assembly. While the α integrin subunit determines extracellular ligand specificity, the ß integrin chain binds to an acidic residue of the ligand, and cytoplasmic adapter protein families such as talins, kindlins and paxillin, to form mechanosensing cell matrix adhesions. Alternative splicing of the ß1 integrin cytoplasmic tail creates ubiquitously expressed ß1A, and the heart and skeletal muscle-specific ß1D form. To study the physiological difference between these forms, we developed fluorescent ß1 integrins and analyzed their dynamics, localization, and cytoplasmic adapter recruitment and effects on cell proliferation. On fibronectin, GFP-tagged ß1A integrin showed dynamic exchange in peripheral focal adhesions, and long, central fibrillar adhesions. In contrast, GFP-ß1D integrins exchanged slowly, forming immobile and short central adhesions. While adhesion recruitment of GFP-ß1A integrin was sensitive to C-terminal tail mutagenesis, GFP-ß1D integrin was recruited independently of the distal NPXY motif. In addition, a P786A mutation in the proximal, talin-binding NPXY783 motif switched ß1D to a highly dynamic integrin. In contrast, the inverse A786P mutation in ß1A integrin interfered with paxillin recruitment and proliferation. Thus, differential ß1 integrin splicing controls integrin-dependent adhesion signaling, to adapt to the specific physiological needs of differentiated muscle cells.

Relationship between symptoms, barriers to care and healthcare utilisation among children under five in rural Mali.

OBJECTIVES: To identify social and structural barriers to timely utilisation of qualified providers among children under five years in a high-mortality setting, rural Mali and to analyse how utilisation varies by symptom manifestation. METHODS: Using baseline household survey data from a cluster-randomised trial, we assessed symptom patterns and healthcare trajectories of 5117 children whose mothers reported fever, diarrhoea, bloody stools, cough and/or fast breathing in the preceding two weeks. We examine associations between socio-demographic factors, symptoms and utilisation outcomes in mixed-effect logistic regressions. RESULTS: Almost half of recently ill children reported multiple symptoms (46.2%). Over half (55.9%) received any treatment, while less than one-quarter (21.7%) received care from a doctor, nurse, midwife, trained community health worker or pharmacist within 24 h of symptom onset. Distance to primary health facility, household wealth and maternal education were consistently associated with better utilisation outcomes. While children with potentially more severe symptoms such as fever and cough with fast breathing or diarrhoea with bloody stools were more likely to receive any care, they were no more likely than children with fever to receive timely care with a qualified provider. CONCLUSIONS: Even distances as short as 2-5 km significantly reduced children's likelihood of utilising healthcare relative to those within 2 km of a facility. While children with symptoms indicative of pneumonia and malaria were more likely to receive any care, suggesting mothers and caregivers recognised potentially severe illness, multiple barriers to care contributed to delays and low utilisation of qualified providers, illustrating the need for improved consideration of barriers.

Effects of a minimum floor Price law on cigarette use in Oakland, California: A static microsimulation model.

Tobacco minimum floor price laws (MFPLs) are a non-tax price policy that set a price below which tobacco products cannot be sold, thereby raising prices. Despite their growing interest among policy makers, little is known about the effects of local MFPLs on smoking prevalence or smoking intensity. We aimed to project the impact of a local tobacco MFPL on cigarette smoking prevalence and cigarette smoking intensity in Oakland, California, including detailed analysis of several important subpopulations. We used data collected between April 2017 and December 2019 from the California Behavioral Risk Factor Surveillance System and the National Youth Tobacco Survey to construct a static microsimulation model representative of Oakland. We projected the impact of MFPLs ranging from $8.00 to $13.00 per pack. All analyses were conducted between 2019 and 2020. With the introduction of an MFPL and assuming 15% policy evasion, mean price paid per pack was projected to increase by $1.05 to $4.69, cigarette smoking prevalence was projected to drop by 0.3% to 0.8%, and smoking intensity was projected to drop by 0.7% to 2.0% among continuing smokers. Total number of cigarettes smoked per month was projected to drop by 246,000 to 734,000 cigarettes, a 3.0% to 9.0% reduction from the current level (8.2 million cigarettes). The greatest reductions in cigarette smoking prevalence were among those aged 12 to 24-years-old, of non-Hispanic black or other race/ethnicity, and living below the federal poverty level. An MFPL in Oakland may substantially reduce cigarette use and target several important subpopulations.

Household factors and under-five mortality in Bankass, Mali: results from a cross-sectional survey.

BACKGROUND: Rural parts of Mali carry a disproportionate burden of the country's high under-five mortality rate. A range of household factors are associated with poor under-five health in resource-limited settings. However, it is unknown which most influence the under-five mortality rate in rural Mali. We aimed to describe household factors associated with under-five mortality in Bankass, a remote region in central Mali. METHODS: We analysed baseline household survey data from a trial being conducted in Bankass. The survey was administered to households between December 2016 and January 2017. Under-five deaths in the five years prior to baseline were documented along with detailed information on household factors and women's birth histories. Factors associated with under-five mortality were analysed using Cox regression. RESULTS: Our study population comprised of 17,408 under-five children from 8322 households. In the five years prior to baseline, the under-five mortality rate was 152.6 per 1000 live births (158.8 and 146.0 per 1000 live births for males and females, respectively). Living a greater distance from a primary health center was associated with a higher probability of under-five mortality for both males (adjusted hazard ratio [aHR] 1.53 for ≥10 km versus < 2 km, 95% confidence interval [CI] 1.25-1.88) and females (aHR 1.59 for ≥10 km versus < 2 km, 95% CI 1.27-1.99). Under-five male mortality was additionally associated with lower household wealth quintile (aHR 1.47 for poorest versus wealthiest, 95%CI 1.21-1.78), lower reading ability among women of reproductive age in the household (aHR 1.73 for cannot read versus can read, 95%CI 1.04-2.86), and living in a household with access to electricity (aHR 1.16 for access versus no access, 95%CI 1.00-1.34). CONCLUSIONS: U5 mortality is very high in Bankass and is associated with living a greater distance from healthcare and several other household factors that may be amenable to intervention or facilitate program targeting.

Can Australia Reach the World Health Organization Hepatitis C Elimination Goal by 2025 Among Human Immunodeficiency Virus-positive Gay and Bisexual Men?

BACKGROUND: Human immunodeficiency virus (HIV)-positive gay and bisexual men (GBM) in Australia are well engaged in care. The World Health Organization's (WHO) hepatitis C virus (HCV) elimination target of an 80% reduction in incidence by 2030 may be reachable ahead of time in this population. METHODS: We predicted the effect of treatment and behavioral changes on HCV incidence among HIV-positive GBM up to 2025 using a HCV transmission model parameterized with Australian data. We assessed the impact of changes in behavior that facilitate HCV transmission in the context of different rates of direct-acting antiviral (DAA) use. RESULTS: HCV incidence in our model increased from 0.7 per 100 person-years in 2000 to 2.5 per 100 person-years in 2016 and had the same trajectory as previously reported clinical data. If the proportion of eligible (HCV RNA positive) patients using DAAs stays at 65% per year between 2016 and 2025, with high-risk sexual behavior and injecting drug use remaining at current levels, HCV incidence would drop to 0.4 per 100 person-years (85% decline from 2016). In the same treatment scenario but with substantial increases in risk behavior, HCV incidence would drop to 0.6 per 100 person-years (76% decline). If the proportion of eligible patients using DAAs dropped from 65% per year in 2016 to 20% per year in 2025 and risk behavior did not change, HCV incidence would drop to 0.7 per 100 person-years (70% reduction). CONCLUSIONS: Reaching the WHO HCV elimination target by 2025 among HIV-positive GBM in Australia is achievable.

Cardiovascular disease among people living with HIV in Brazil.

OBJECTIVES: There is a paucity of data on cardiovascular disease (CVD) among people living with HIV (PLHIV) in resource-limited countries. We assessed factors associated with CVD and the impact of prevalent CVD on all-cause mortality in PLHIV on antiretroviral therapy in Brazil. METHODS: Competing risk regression to assess factors associated with CVD and all-cause mortality in the HIV-Brazil Cohort Study between 2003 and 2014. RESULTS: Among 5614 patients, the rate of CVD was 3.5 (95% confidence interval [95% CI] 2.9-4.3) per 1000 person-years. CVD was associated with older age (adjusted hazard ratio [aHR] 6.4 for ≥55 years vs. <35 years, 95% CI: 2.5-16.3, P < 0.01), black race (aHR 1.8 vs. white race, 95% CI: 1.0-3.1, P = 0.04), past CVD (aHR 3.0 vs. no past CVD, 95% CI: 1.4-6.2, P < 0.01), hypertension (aHR 1.8 vs. no hypertension, 95% CI: 1.0-3.1, P = 0.04), high-grade dyslipidemia (aHR 9.3 vs. no high-grade dyslipidemia, 95% CI: 6.0-14.6, P < 0.01), ever smoking (aHR 2.4 vs. never, 95% CI: 1.2-5.0, P = 0.02) and low nadir CD4 cell count (aHR 1.8 for 100-250 cells/mm3 vs. >250 cells/mm3 , 95% CI: 1.0-3.2, P = 0.05). The rate of death was 16.6 (95% CI: 15.1-18.3) per 1000 person-years. Death was strongly associated with having had a past CVD event (aHR 1.7 vs. no past CVD event, 95% CI: 1.1-2.7, P = 0.01). CONCLUSIONS: Traditional and HIV-specific factors associated with CVD among PLHIV in Brazil are similar to those identified among PLHIV in high-income countries. PLHIV in Brazil with a history of CVD have a high risk of death. CVD care and treatment remain priorities for PLHIV in Brazil as this population ages and antiretroviral therapy use expands.

OBJECTIFS: Il existe peu de données sur les maladies cardiovasculaires (MCV) chez les personnes vivant avec le VIH (PVVIH) dans les pays à ressources limitées. Nous avons évalué les facteurs associés aux MCV et l'impact des MCV prévalentes sur la mortalité toutes causes confondues des PVVIH sous le traitement antirétroviral au Brésil. MÉTHODES: Régression des risques concurrente pour évaluer les facteurs associés aux MCV et à la mortalité toutes causes confondues dans l'étude de cohorte VIH-Brésil entre 2003 et 2014. RÉSULTATS: Parmi 5.614 patients, le taux de MCV était de 3,5 (intervalle de confiance à 95% [IC95%] 2,9-4,3) pour 1.000 personnes-années. Les MCV étaient associées à un âge plus avancé (rapport de risque ajusté [aHR] 6,4 chez les ≥55 ans versus chez les <35 ans, IC95%: 2,5-16,3 ; p <0,01), race noire (aHR: 1,8 versus race blanche, IC95%: 1,0-3,1 ; p = 0,04), MCV passée (aHR: 3,0 versus pas de MCV passée, IC95%: 1,4-6,2 ; p <0,01), hypertension (aHR: 1,8 versus pas d'hypertension, IC95%: 1,0-3,1 ; p = 0,04), dyslipidémie de grade élevé (aHR 9,3 versus absence de dyslipidémie de grade élevé, IC95%: 6,0-14,6 ; p <0,01), tabagisme (aHR 2,4 versus n'avoir jamais fumé, IC95%: 1,2-5,0 ; p = 0,02) et faible nombre de CD4 au nadir (aHR: 1,8 pour 100-250 cellules/mm3 versus >250 cellules/mm3 , IC95%: 1,0-3,2 ; p = 0,05). Le taux de décès était de 16,6 (IC95%: 15,1-18,3) pour 1.000 personnes-années. Le décès était fortement associé à un événement MCV antérieur (aHR: 1,7 versus aucun événement MCV antérieur, IC95%: 1,1-2,7 ; p = 0,01). CONCLUSIONS: Les facteurs traditionnels et spécifiques au VIH associés aux MCV chez les PVVIH au Brésil sont similaires à ceux identifiés chez les PVVIH dans les pays à revenu élevé. Les PVVIH au Brésil ayant des antécédents de MCV ont un risque élevé de décès. Les soins et le traitement des MCV restent des priorités pour les PVVIH au Brésil à mesure que cette population vieillit et que l'utilisation des thérapies antirétrovirales augmente.

Cigarette Pack Prices and Sales Following Policy Changes in California, 2011-2018.

Objectives. To estimate the combined effect of California's Tobacco 21 law (enacted June 2016) and $2-per-pack cigarette excise tax increase (enacted April 2017) on cigarette prices and sales, compared with matched comparator states.Methods. We used synthetic control methods to compare cigarette prices and sales after the policies were enacted, relative to what we would have expected without the policy reforms. To estimate the counterfactual, we matched pre-reform covariate and outcome trends between California and control states to construct a "synthetic" California.Results. Compared with the synthetic control in 2018, cigarette prices in California were $1.89 higher ($7.86 vs $5.97; P < .001), and cigarette sales were 16.6% lower (19.9 vs 16.6 packs per capita; P < .001). This reduction in sales equates to 153.9 million fewer packs being sold between 2017 and 2018.Conclusions. California's new cigarette tax was largely passed on to consumers. The new cigarette tax, combined with the Tobacco 21 law, have contributed to a rapid and substantial reduction in cigarette consumption in California.

Changes in renal function with long-term exposure to antiretroviral therapy in HIV-infected adults in Asia.

PURPOSE: Renal disease is common among people living with human immunodeficiency virus (HIV). However, there is limited information on the incidence and risk factors associated with renal dysfunction among this population in Asia. METHODS: We used data from the TREAT Asia HIV Observational Database. Patients were included if they started antiretroviral therapy during or after 2003, had a serum creatinine measurement at antiretroviral therapy initiation (baseline), and had at least 2 follow-up creatinine measurements taken ≥3 months apart. Patients with a baseline estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73 m2 were excluded. Chronic kidney disease was defined as 2 consecutive eGFR values ≤60 mL/min/1.73 m2 taken ≥3 months apart. Generalized estimating equations were used to identify factors associated with eGFR change. Competing risk regression adjusted for study site, age and sex, and cumulative incidence plots were used to evaluate factors associated with chronic kidney disease (CKD). RESULTS: Of 2547 patients eligible for this analysis, tenofovir was being used by 703 (27.6%) at baseline. Tenofovir use, high baseline eGFR, advanced HIV disease stage, and low nadir CD4 were associated with a decrease in eGFR during follow-up. Chronic kidney disease occurred at a rate of 3.4 per 1000 patient/years. Factors associated with CKD were tenofovir use, old age, low baseline eGFR, low nadir CD4, and protease inhibitor use. CONCLUSIONS: There is an urgent need to enhance renal monitoring and management capacity among at-risk groups in Asia and improve access to less nephrotoxic antiretrovirals.

Prediction Model of Pre-treatment HIV RNA Levels in Naïve Thai HIV-infected Patients: Application for Resource-limited Settings.

A prediction model for pretreatment HIV RNA level ≤100,000 copies/ml would provide a useful tool for selection of abacavir (ABC) or rilpivirine (RPV) in the first-line regimen in a resource-limited setting. Factors associated with pre-treatment HIV RNA ≤100,000 copies/ml were determined from a cohort of 1,223 patients divided into a derivation (n = 873) and the remaining in a validation group. Their median [interquartile range (IQR)] age was 36.3 (30.5-42.9) years, CD4 count 122 (39-216) cells/mm3 and pre-treatment HIV RNA level 100,000 (32,449-229,777) copies/ml. Factors associated with pretreatment HIV RNA ≤100,000 copies/ml were non-anemia [odds ratio (OR)= 2.05; 95% confidence interval (CI): 1.28-3.27, p= 0.003], CD4 count ≥200 cells/mm3 (OR= 3.00; 95% CI: 2.08-4.33, p<0.001) and non-heterosexual HIV exposure (OR= 1.61; 95% CI: 1.07-2.43, p= 0.021). The area under a receiver operating characteristic curve was 0.66 (95% CI: 0.62-0.69), but specificity was 97.3%. The prediction model identified a set of readily available clinical data but lacked the requisite predictive performance to fulfill its purpose.

Hepatitis C testing and re-testing among people attending sexual health services in Australia, and hepatitis C incidence among people with human immunodeficiency virus: analysis of national sentinel surveillance data.

BACKGROUND: Direct acting antivirals are expected to drastically reduce the burden of hepatitis C virus (HCV) in people living with Human Immunodeficiency Virus (HIV). However, rates of HCV testing, re-testing and incident infection in this group remain uncertain in Australia. We assessed trends in HCV testing, re-testing and incident infection among HIV-positive individuals, and evaluated factors associated with HCV re-testing and incident infection. METHODS: The study population consisted of HIV-positive individuals who visited a sexual health service involved in the Australian Collaboration for Coordinated Enhanced Sentinel Surveillance (ACCESS) between 2007 and 2015. Poisson regression was used to assess trends and to evaluate factors associated with HCV re-testing and incident HCV infection. RESULTS: There were 9227 HIV-positive individuals included in our testing rate analysis. Of 3799 HIV-positive/HCV-negative people that attended an ACCESS sexual health service more than once, 2079 (54.7%) were re-tested for HCV and were therefore eligible for our incidence analysis. The rate of HCV testing increased from 17.1 to 51.4 tests per 100 patient years between 2007 and 2015 (p for trend <0.01). Over the same period, HCV re-testing rates increased from 23.9 to 79.7 tests per 100 person years (p for trend <0.01). A clear increase in testing and re-testing began after 2011. Patients who identified as men who have sex with men and those with a history of injecting drug use experienced high rates of HCV re-testing over the course of the study period. Among those who re-tested, 157 incident HCV infections occurred at a rate of 2.5 events per 100 person years. Between 2007 and 2009, 2010-2011, 2012-2013 and 2014-2015, rates of incident HCV were 0.8, 1.5, 3.9 and 2.7 events per 100 person years, respectively (p for trend <0.01). Incident HCV was strongly associated with a history of injecting drug use. CONCLUSIONS: High rates of HCV testing and re-testing among HIV-positive individuals in Australia will assist strategies to achieve HCV elimination through rapid treatment scale up. Continued monitoring of HCV incidence in this population is essential for guiding both HCV prevention and treatment strategies.

The Reliability, Validity and Responsiveness of Two Disease Scores (BPDAI and ABSIS) for Bullous Pemphigoid: Which One to Use?

A significant obstacle in guiding evidence-based management of bullous pemphigoid (BP) is the lack of a standardised, validated scoring system for the condition. The aim of this study is to evaluate the suitability of the Bullous Pemphigoid Disease Area Index (BPDAI) and the Autoimmune Bullous Skin disorder Intensity Score (ABSIS) as outcome measures for BP in clinical trials. Thirty-two BP patients were repeatedly assessed over four years using Physician Global Assessment (PGA), anti-BP180 ELISA titres, BPDAI, ABSIS, BPDAI-Pruritus, Autoimmune Bullous Disease Quality of Life (ABQOL) and Treatment of Autoimmune Bullous Disease Quality of Life (TABQOL) questionnaires. The reliability, validity, responsiveness, and minimal clinically important differences (MCIDs) were calculated. For inter-rater reliability, the intraclass correlation coefficients (95% CI) were: BPDAI 0.957 (0.901-0.982) and ABSIS 0.881 (0.736-0.949). Compared to ABSIS, BPDAI was better correlated with PGA(r = 0.875, p < 0.001), BPDAI-Pruritus (r=0.632, p = 0.004), ABQOL (r = 0.521, p = 0.011) and TABQOL (r=0.538, p = 0.008). MCIDs for BPDAI were 4-points for assessing clinical improvement and 3-points for deterioration. ABSIS demonstrated less responsiveness with MCIDs at 8.6-points for improvement and 4-points for deterioration. These results indicate that BPDAI demonstrated excellent reliability, validity and responsiveness, while ABSIS had moderate to good reliability, validity and responsiveness.

Factors associated with pre-treatment HIV RNA: application for the use of abacavir and rilpivirine as the first-line regimen for HIV-infected patients in resource-limited settings.

BACKGROUND: Abacavir and rilpivirine are alternative antiretroviral drugs for treatment-naïve HIV-infected patients. However, both drugs are only recommended for the patients who have pre-treatment HIV RNA <100,000 copies/mL. In resource-limited settings, pre-treatment HIV RNA is not routinely performed and not widely available. The aims of this study are to determine factors associated with pre-treatment HIV RNA <100,000 copies/mL and to construct a model to predict this outcome. METHODS: HIV-infected adults enrolled in the TREAT Asia HIV Observational Database were eligible if they had an HIV RNA measurement documented at the time of ART initiation. The dataset was randomly split into a derivation data set (75% of patients) and a validation data set (25%). Factors associated with pre-treatment HIV RNA <100,000 copies/mL were evaluated by logistic regression adjusted for study site. A prediction model and prediction scores were created. RESULTS: A total of 2592 patients were enrolled for the analysis. Median [interquartile range (IQR)] age was 35.8 (29.9-42.5) years; CD4 count was 147 (50-248) cells/mm3; and pre-treatment HIV RNA was 100,000 (34,045-301,075) copies/mL. Factors associated with pre-treatment HIV RNA <100,000 copies/mL were age <30 years [OR 1.40 vs. 41-50 years; 95% confidence interval (CI) 1.10-1.80, p = 0.01], body mass index >30 kg/m2 (OR 2.4 vs. <18.5 kg/m2; 95% CI 1.1-5.1, p = 0.02), anemia (OR 1.70; 95% CI 1.40-2.10, p < 0.01), CD4 count >350 cells/mm3 (OR 3.9 vs. <100 cells/mm3; 95% CI 2.0-4.1, p < 0.01), total lymphocyte count >2000 cells/mm3 (OR 1.7 vs. <1000 cells/mm3; 95% CI 1.3-2.3, p < 0.01), and no prior AIDS-defining illness (OR 1.8; 95% CI 1.5-2.3, p < 0.01). Receiver-operator characteristic (ROC) analysis yielded area under the curve of 0.70 (95% CI 0.67-0.72) among derivation patients and 0.69 (95% CI 0.65-0.74) among validation patients. A cut off score >25 yielded the sensitivity of 46.7%, specificity of 79.1%, positive predictive value of 67.7%, and negative predictive value of 61.2% for prediction of pre-treatment HIV RNA <100,000 copies/mL among derivation patients. CONCLUSION: A model prediction for pre-treatment HIV RNA <100,000 copies/mL produced an area under the ROC curve of 0.70. A larger sample size for prediction model development as well as for model validation is warranted.

Early Height and Weight Changes in Children Using Cotrimoxazole Prophylaxis With Antiretroviral Therapy.

BACKGROUND: The growth benefits of cotrimoxazole during early antiretroviral therapy (ART) are not well characterized. METHODS: Individuals enrolled in the Therapeutics Research, Education, and AIDS Training in Asia Pediatric HIV Observational Database were included if they started ART at ages 1 month-14 years and had both height and weight measurements available at ART initiation (baseline). Generalized estimating equations were used to identify factors associated with change in height-for-age z-score (HAZ), follow-up HAZ ≥ -2, change in weight-for-age z-score (WAZ), and follow-up WAZ ≥ -2. RESULTS: A total of 3217 children were eligible for analysis. The adjusted mean change in HAZ among cotrimoxazole and non-cotrimoxazole users did not differ significantly over the first 24 months of ART. In children who were stunted (HAZ < -2) at baseline, cotrimoxazole use was not associated with a follow-up HAZ ≥ -2. The adjusted mean change in WAZ among children with a baseline CD4 percentage (CD4%) >25% became significantly different between cotrimoxazole and non-cotrimoxazole users after 6 months of ART and remained significant after 24 months (overall P < .01). Similar changes in WAZ were observed in those with a baseline CD4% between 10% and 24% (overall P < .01). Cotrimoxazole use was not associated with a significant difference in follow-up WAZ in children with a baseline CD4% <10%. In those underweight (WAZ < -2) at baseline, cotrimoxazole use was associated with a follow-up WAZ ≥ -2 (adjusted odds ratio, 1.70 vs not using cotrimoxazole [95% confidence interval, 1.28-2.25], P < .01). This association was driven by children with a baseline CD4% ≥10%. CONCLUSIONS: Cotrimoxazole use is associated with benefits to WAZ but not HAZ during early ART in Asian children.