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.

Outcomes in Medicare-ineligible people living with human immunodeficiency virus in a large healthcare network in Melbourne 2004-2019.

Australia has approximately 1.6 million Medicare-ineligible residents, of whom around 450 are living with human immunodeficiency virus (PLHIV). We examined the outcomes in a cohort of 50 Medicare-ineligible patients presenting to our hospital network over a 15-year period: 31 women (62%) and 19 men. Twenty-four were newly diagnosed. Sixteen of 24 remained in Australia more than 1 year after diagnosis. Although the mean CD4 count at initial contact was 353 cells/mm3 (range 3-2228; standard deviation (SD) = 452.88), 13 people required treatment for opportunistic infections and 21 people required hospital admissions related to HIV, incurring total estimated hospital costs of $886 310. The mean number of contact years spent with the service was 2.2 (range 0-12; SD = 2.6) and 20 people remain under care. Twenty-seven PLHIV remain in Australia, seven have transferred care within Australia, two people are known to have died and eight are lost to follow up. The median number of admissions was 0 (range 0-4; SD = 1) and median length of admission was 5 days (range 0-73; SD = 19). Many people leave Australia shortly after a diagnosis of HIV, but most Medicare-ineligible PLHIV remain. Delays in diagnosing HIV and acquiring Medicare status are associated with a significant burden of disease and cost. Keeping people well, on therapy and out of hospital is likely to be cost-saving in addition to good clinical practice.

Clinical and financial burden of spinal infections in people who inject drugs.

BACKGROUND: People who inject drugs (PWID) are known to be at increased risk of infectious diseases including bacterial and blood-borne viral infections. However, there is limited literature surrounding the burden of spinal infections as a complication of injecting drug use (IDU). AIMS: To quantify the clinical and financial burden of IDU-related spinal infections. METHODS: Retrospective chart review of adult PWID with spinal infections requiring hospital admission to a tertiary health service in Melbourne, Australia between 2011 and 2019. RESULTS: Fifty-seven PWID with 63 episodes of spinal infections were identified with a median hospital stay of 47 days (interquartile range (IQR) 16; range 4-243 days). One-third of episodes required neurosurgical intervention and 11 (17%) episodes required intensive care unit admission (range 2-17 days). Staphylococcus aureus was the most common causative pathogen, present in three-quarters of all episodes (n = 47). The median duration of antibiotic regime was 59 days (IQR 42) and longer courses were associated with known bacteraemia (P = 0.048), polymicrobial infections (P = 0.001) and active IDU (P = 0.066). Predictors of surgery include neurological symptoms at presentation (relative risk (RR) 2.6; P = 0.010), inactive IDU status (RR 3.0; P = 0.002), a diagnosis of epidural abscess (RR 4.1; P = 0.001) and spinal abscess (RR ∞; P < 0.001). Completion of planned antimicrobial therapy was reported in 51 (82%) episodes. Average expenditure per episode was  A$61 577. CONCLUSIONS: Spinal infections in PWID are an underreported serious medical complication of IDU. Although mortality is low, there is significant morbidity with prolonged admissions, large antimicrobial requirements and surgical interventions generating a substantial cost to the health system.

SARS-COV-2 vaccine acceptance in patients with rheumatic diseases: a cross-sectional study.

OBJECTIVES: To evaluate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine acceptance among patients with rheumatic diseases (RMD). METHODS: All rheumatology patients attending a large suburban health network were invited to participate in an anonymized online survey. The primary outcome of interest was SARS-COV-2 vaccine acceptance. RESULTS: The mean (SD) age of respondents (n = 641) was 52.7 (15.1) years and 74.4% (n = 474) were female. Sixty-five percent were willing to have a SARS-COV-2 vaccine, while 34.4% were vaccine-hesitant (unwilling or undecided). On multivariate analysis, vaccine acceptance was associated with smoking (OR: 2.25 [95% CI: 1.22-4.15; p = .009]), history of malignancy (OR: 2.51 [95% CI: 1.19-5.26; p = .015]), influenza or pneumococcal vaccination in the preceding year (OR: 2.69 [95% CI: 1.78-4.05; p < .001]) and number of COVID-Safe measures practiced (OR: 1.54 [95% CI: 1.05-2.26; p = .027]). Vaccine acceptance correlated with positive beliefs regarding vaccine efficacy (r = 0.40; p < .001) and safety (r = 0.36; p < .001). Vaccine acceptance correlated negatively with concerns regarding side-effects (r = -0.30; p < .001) and vaccine-associated RMD flare (r = -0.21; p < .001). In vaccine-hesitant respondents, 39.2% were more likely to accept vaccination if given a choice of which vaccine they receive and 54.5% if their rheumatologist recommended it. Twenty-seven percent of patients on immunomodulators were willing to withhold medications while 42.1% were willing if advised by their rheumatologist. CONCLUSION: SARS-COV-2 vaccine hesitancy is prevalent amongst RMD patients and associated with concerns regarding vaccine safety, efficacy, side effects and RMD flare. Clinician recommendation, vaccine choice and communications targeting patient concerns could facilitate vaccine acceptance.Significance and Innovations Vaccine hesitancy is prevalent in RMD patientsVaccine acceptance is associated with beliefs regarding vaccine safety and efficacy and concerns regarding RMD flare and vaccine-associated side effectsVaccine choice and clinician recommendation have the potential to improve vaccine acceptance in patients who are hesitant.

HIV is associated with an increased risk of age-related clonal hematopoiesis among older adults.

People with human immunodeficiency virus (HIV) have higher rates of certain comorbidities, particularly cardiovascular disease and cancer, than people without HIV1-5. In view of observations that somatic mutations associated with age-related clonal hematopoiesis (CH) are linked to similar comorbidities in the general population6-10, we hypothesized that CH may be more prevalent in people with HIV. To address this issue, we established a prospective cohort study, the ARCHIVE study (NCT04641013), in which 220 HIV-positive and 226 HIV-negative participants aged 55 years or older were recruited in Australia. Demographic characteristics, clinical data and peripheral blood were collected to assess the presence of CH mutations and to identify potential risk factors for and clinical sequelae of CH. In total, 135 CH mutations were identified in 100 (22.4%) of 446 participants. CH was more prevalent in HIV-positive participants than in HIV-negative participants (28.2% versus 16.8%, P = 0.004), overall and across all age groups; the adjusted odds ratio for having CH in those with HIV was 2.16 (95% confidence interval 1.34-3.48, P = 0.002). The most common genes mutated overall were DNMT3A (47.4%), TET2 (20.0%) and ASXL1 (13.3%). CH and HIV infection were independently associated with increases in blood parameters and biomarkers associated with inflammation. These data suggest a selective advantage for the emergence of CH in the context of chronic infection and inflammation related to HIV infection.

Underutilised human immunodeficiency virus testing in the setting of invasive pneumococcal disease.

People living with human immunodeficiency virus (HIV) are at increased risk of invasive pneumococcal disease (IPD). We assessed whether patients with invasive Streptococcus pneumoniae, in blood or cerebrospinal fluid, underwent HIV serology testing over a 5-year period. We found that only 39 inpatients out of 156 (25%) with IPD were tested for HIV and thus conclude that such testing is not being undertaken according to some guidelines in patients with IPD. Education and implementation strategies are required to increase testing.

Platelet phenotype and function in the absence of splenic sequestration (Review).

The spleen, in addition to its role in immunity, plays key roles in erythrocyte maintenance and platelet sequestration. Loss of the spleen via splenectomy occurs in approximately 6.4 to 7.1 per 100 000 people per year globally, commonly as a life-saving emergency procedure in trauma and a therapeutic procedure in hematological and hematological malignant conditions. It is associated with increased risk of life-threatening infection and thromboembolism, presumably via loss of splenic function, but the underlying mechanisms behind post-splenectomy thromboembolism are unclear. The splenectomized individual has a two-fold risk of thromboembolism as compared to non-splenectomized individuals and the risk of thromboembolism is elevated both post-operatively and in the longer term. Although those splenectomized for hematological conditions or hematological malignant conditions are at highest risk for thromboembolism, an increase in thromboembolic outcomes is also observed amongst individuals splenectomized for trauma, suggesting underlying disease state is only a partial factor. Although the physiological role of the splenic platelet pool on platelets is unclear, platelet changes after splenectomy suggest that the spleen may play a role in maintaining platelet quality and function. In hypersplenic conditions, sequestration can increase to sequester up to 72% of the total platelet mass. Following splenectomy, a thrombocytosis is commonly seen secondary to the loss of the ability to sequester platelets. Abnormal platelet quality and function have been observed as a consequence of splenectomy. These platelet defects seen after splenectomy may likely contribute to the increase in post-splenectomy thromboembolism. Here we draw upon the literature to characterize the post-splenectomy platelet and its potential role in post-splenectomy thromboembolism.

Burden of infective endocarditis in an Australian cohort of people who inject drugs.

BACKGROUND: Infective endocarditis (IE) results in substantial morbidity and mortality in people who inject drugs (PWID). AIMS: To describe the burden of IE and its outcomes in PWID. METHODS: Retrospective cohort study of adults admitted to a tertiary referral centre in Melbourne, Australia, with IE due to injection drug use from 1997 to 2015. RESULTS: Ninety-seven PWID with 127 episodes of IE were identified with a median acute inpatient stay of 37 days (1-84). Admission to an intensive care unit was required in 67/127 (53%) episodes. Twenty-seven percent (34/127) of episodes occurred in patients with a previous episode of endocarditis. One third (43/127, 34%) of episodes involved left-sided cardiac valves. Antimicrobial treatment was completed in 88 (70%) episodes. Valve surgery was performed in 25/127 (20%) episodes. Predictors of surgery in univariable analysis were left-sided cardiac involvement (risk ratio (RR) 6.0), severe valvular regurgitation (RR 2.6) and cardiac failure (RR 2.2) (all P < 0.005). Twenty (16%) episodes resulted in death. Predictors of mortality on univariable analysis were left-sided cardiac involvement (RR 6.4), and not completing treatment (RR 0.12; both P < 0.001). The average estimated cost per episode was AU$74 168. CONCLUSIONS: IE causes a considerable burden of disease in PWID, with significant healthcare utilisation and cost. Surgery and death are not infrequent complications. In addition to ensuring completion of antimicrobial therapy, strategies such as opioid maintenance programmes may be useful in improving health outcomes for PWID.

Human immunodeficiency virus-infected young people in Australia: data from the Australian HIV Observational Database.

BACKGROUND: Individuals aged 13-24 years undergo vast physical, cognitive, social and psychological changes. Australian data regarding clinical outcomes of those diagnosed with HIV in this age are sparse. AIM: We aimed to describe demographic factors, virologic and clinical outcomes of individuals aged 13-24 years diagnosed with human immunodeficiency virus (HIV). METHODS: Patients diagnosed with HIV after 1997 in the Australian HIV Observational Database were divided into young adults, diagnosed at age <25 years (n = 223), and older adults (n = 1957). Demographic and clinical factors were compared between groups. RESULTS: Young adults had a median age at diagnosis of 22 years (inter quartile range (IQR) 20-24) and median age at treatment initiation of 24 years (IQR 22-26). They were more likely to be female than the older cohort (21.1 vs 10.8%; P < 0.001). Men who have sex with men was the most common exposure category in both groups. CD4 count at diagnosis was significantly higher in younger than older adults (median 460 vs 400 cells/mm3 , P = 0.006), whereas HIV viral load at diagnosis was lower (35 400 vs 61 659 copies/mL, P = 0.011). The rate of loss to follow up (LTFU) was higher in young adults (8.0 vs 4.3 per 100PY, P < 0.001). Young adults were more likely to have a treatment interruption compared to older adults (5.3 vs 4.0 per 100PY, P = 0.039). Rates of treatment switch, time to treatment change, and CD4 and viral load responses to treatment were similar between groups. CONCLUSIONS: Young adults were diagnosed with HIV at higher CD4 counts and lower viral loads than their older counterparts. LTFU and treatment interruption were more common highlighting the need for extra efforts directed towards retention in care and education regarding the risks of treatment interruptions.

High rates of potentially infectious exposures between immunocompromised patients and their companion animals: an unmet need for education.

A cross-sectional survey of 265 adult patients with haematological malignancy, haemoglobinopathy or human immunodeficiency virus was performed to determine the potential risk of infection from animal exposures. One hundred and thirty-seven (52%) owned an animal; the majority were dogs (74%) and cats (39%), but 14% owned birds and 3% reptiles. Eighty percent engaged in behaviour with their animals that potentially put them at risk of zoonotic infections. The most frequent behaviours were picking up animal faeces 72 (52%), cleaning animal areas 69 (50%) and allowing animals to sleep in the same bed 51 (37%). Twenty-eight percent allowed the animal to lick their face. Of all patients, 80 (30%) had been bitten or scratched by an animal. Only 16% of those who owned pets could recall receiving education regarding safe behaviours around animals. These immunocompromised patients are at risk of infection through exposure to pets. Our study highlights the need for increased education of patients regarding how to remain safe around their pets.

Surveillance of life-long antibiotics: a review of antibiotic prescribing practices in an Australian Healthcare Network.

BACKGROUND: The rise of antimicrobial use in the twentieth century has significantly reduced morbidity due to infection, however it has also brought with it the rise of increasing resistance. Some patients are on prolonged, if not "life-long" course of antibiotics. The reasons for this are varied, and include non-infectious indications. We aimed to study the characteristics of this potential source of antibiotic resistance, by exploring the antibiotic dispensing practices and describing the population of patients on long-term antibiotic therapy. METHODS: A retrospective cross-sectional study of antibiotic dispensing records was performed at a large university hospital-based healthcare network in Melbourne, Australia. Outpatient prescriptions were extracted from the hospital pharmacy database over a 6 month period in 2014. Medical records of these patients were reviewed to determine the indication for prescription, including microbiology, the intended duration, and the prescribing unit. A descriptive analysis was performed on this data. RESULTS: 66,127 dispensing episodes were reviewed. 202 patients were found to have been prescribed 1 or more antibiotics with an intended duration of 1 year or longer. 69/202 (34%) of these patients were prescribed prolonged antibiotics for primary prophylaxis in the setting of immunosuppression. 43/202 (21%) patients were prescribed long-term suppressive antibiotics for infections of thought incurable (e.g. vascular graft infections), and 34/43 (79%) were prescribed by Infectious Diseases doctors. 66/202 (33%) patients with cystic fibrosis were prescribed prolonged courses of macrolides or fluoroquinolones, by respiratory physicians. There was great heterogeneity noted in indications for prolonged antibiotic courses, as well as antibiotic agents utilised. CONCLUSION: Our study found that that continuous antibiotic therapy represented only a small proportion of overall antibiotic prescribing at our health network. Prolonged courses of antibiotics were used mainly to suppress infections thought incurable, but also as primary and secondary prophylaxis and as anti-inflammatory agents. More research is needed to understand the impact of long-term antibiotic consumption on both patients and microbial ecology.

Mycobacterium haemophilum bone and joint infection in HIV/AIDS: case report and literature review.

We report a case of disseminated Mycobacterium haemophilum osteomyelitis in a patient with advanced HIV infection, who later developed recurrent immune reconstitution inflammatory syndrome after commencement of antiretroviral therapy. We review previous reports of M. haemophilum bone and joint infection associated with HIV infection and describe the management of M. haemophilum-associated immune reconstitution inflammatory syndrome, including the role of surgery as an adjunctive treatment modality and the potential drug interactions between antiretroviral and antimycobacterial agents.

Acanthamoeba encephalitis: isolation of genotype T1 in mycobacterial liquid culture medium.

We report a case of Acanthamoeba encephalitis diagnosed from an antemortem brain biopsy specimen, where the organism was first isolated in mycobacterial liquid medium and first identified by using a sequence generated by a commercial panfungal sequencing assay. We correlate susceptibility results with clinical outcome.

The inside story. Physicians' views on digital ano-rectal examination for anal cancer screening of HIV positive men who have sex with men.

OBJECTIVE: Anal cancer is relatively common amongst HIV positive men who have sex with men (MSM), but little is known about the anal cancer screening practices of HIV physicians, and whether digital ano-rectal examination (DARE) is utilized for this. To determine the practice of anal cancer screening among HIV physicians, and to identify any barriers for implementing DARE as a method for anal cancer screening. METHODS: 36 physicians from a sexual health centre, 2 tertiary hospital infectious diseases outpatient clinics, and 2 general practices completed a questionnaire on their practice of anal cancer screening amongst HIV positive MSM. Physicians were asked about their confidence in using DARE for anal cancer screening, and whether they perceived barriers to implementing this in their clinic. RESULTS: Most physicians (86%, 95% CI: 71-95) thought that anal cancer screening was important, but only 22% (95% CI: 10-39) were currently screening. Reasons for not screening were the absence of guidelines (87%, 95% CI: 60-98), lack of time (47%, 95% CI: 30-65), and concern about patient acceptability of DARE (32%, 95% CI: 17-51). Whilst 67% (95% CI: 49-81) of physicians felt confident in performing a DARE, only 22% (95% CI: 10-39) were confident in recognizing anal cancer using DARE. CONCLUSION: Although HIV physicians were aware of the need for anal cancer screening among the HIV + MSM population, few were routinely screening. If DARE were to be incorporated into routine HIV care, guidelines recommending screening and up-skilling of HIV physicians to recognize anal cancer are needed.

HIV replication alters the composition of extrinsic pathway coagulation factors and increases thrombin generation.

BACKGROUND: HIV infection leads to activation of coagulation, which may increase the risk for atherosclerosis and venous thromboembolic disease. We hypothesized that HIV replication increases coagulation potentially through alterations in extrinsic pathway factors. METHODS AND RESULTS: Extrinsic pathway factors were measured among a subset of HIV participants from the Strategies for Management of Anti-Retroviral Therapy (SMART) trial. Thrombin generation was estimated using validated computational modeling based on factor composition. We characterized the effect of antiretroviral therapy (ART) treatment versus the untreated state (HIV replication) via 3 separate analyses: (1) a cross-sectional comparison of those on and off ART (n=717); (2) a randomized comparison of deferring versus starting ART (n=217); and (3) a randomized comparison of stopping versus continuing ART (n=500). Compared with viral suppression, HIV replication consistently showed short-term increases in some procoagulants (eg, 15% to 23% higher FVIII; P<0.001) and decreases in key anticoagulants (eg, 5% to 9% lower antithrombin [AT] and 6% to 10% lower protein C; P<0.01). The net effect of HIV replication was to increase coagulation potential (eg, 24% to 48% greater thrombin generation from computational models; P<0.01 for all). The pattern of changes from HIV replication was reversed with ART treatment and consistent across all 3 independent comparisons. CONCLUSIONS: HIV replication leads to complex changes in extrinsic pathway factors, with the net effect of increasing coagulation potential to a degree that may be clinically relevant. The key influence of changes in FVIII and AT suggests that HIV-related coagulation abnormalities may involve changes in hepatocyte function in the context of systemic inflammation.