The burden of skin and soft tissue, bone and joint infections in an Australian cohort of people who inject drugs.

INTRODUCTION: There are currently limited data regarding the clinical and economic significance of skin and soft tissue infections (SSTI) and bone and joint infections in Australian people who inject drugs (PWID). METHODS: Retrospective cohort study in adult PWID admitted to Monash Health, a large heath care network with six hospitals in Victoria, Australia. Inpatients were identified using administrative datasets and International Classification of Disease (ICD-10) coding for specific infection-related conditions. Cost analysis was based on mean ward, intensive care and hospital-in-the-home (HITH) lengths of stay. Spinal infections and endocarditis were excluded as part of previous studies. RESULTS: A total of 185 PWID (61 female, 124 male, median age 37) meeting the study criteria were admitted to Monash Health between January 2010 and January 2021. Admitting diagnoses included 78 skin abscesses, 80 cellulitis, 17 septic arthritis, 4 osteomyelitis, 3 thrombophlebitis and 1 each of necrotising fasciitis, vasculitis and myositis. Pain (87.5%) and swelling (75.1%) were the most common presenting complaints. Opioids (67.4%) and methamphetamine (37.5%) were the most common primary drugs injected. Almost half (46.5%) of patients had concurrent active hepatitis C (HCV) infection on admission. Hepatitis B (HBV) and Human Immunodeficiency Virus (HIV) were uncommon. The most significant causative organism was methicillin-susceptible Staphylococcus aureus (24.9%). In 40.0% (74/185) no organism was identified. Patients required a median acute hospital stay of 5 days (2-51 days). There were 15 patients admitted to the intensive care unit (ICU) with median duration 2 days. PICC line insertion for antibiotics was required in 16.8% of patients, while 51.4% required surgical intervention. Median duration of both oral and IV antibiotic therapy was 11 days. Almost half (48.6%) of patients were enrolled in an opioid maintenance program on discharge. Average estimated expenditure was AUD $16, 528 per admission. CONCLUSION: Skin and soft tissue and joint infections are a major cause of morbidity for PWID. Admission to hospital provides opportunistic involvement of addiction specialty services.

The potential role of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) single-tablet regimen in the expanding spectrum of fixed-dose combination therapy for HIV.

Single-tablet regimens (STRs) of highly safe and effective combination antiretroviral therapy (cART) have had a significant beneficial impact on the clinical outcomes and lives of people living with HIV (PLHIV). As a consequence, healthcare professionals caring for PLHIV in high-income countries have increasingly focused on issues beyond those related to HIV itself, i.e. HIV-related neurological disease, or associated opportunistic infections, which include co-infections, and primarily age- and lifestyle-related comorbidities such as cardiovascular disease, diabetes mellitus, renal impairment, osteoporosis and frailty. This review considers drug side effects and comorbidities seen in PLHIV and evaluates the role of a recently licensed STR - bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) - in mitigating some of those challenges. Factors that need to be evaluated for initial cART regimens include: pretreatment CD4 cell count; plasma HIV RNA; HIV drug resistance; hepatitis B co-infection; HLA-B*5701 status; drug-drug interactions; pregnancy and pregnancy potential; psychiatric and physical comorbidities such as renal or bone disease, as well as simplicity and adherence-friendliness, all of which need to be considered in all lines of therapy. BIC/FTC/TAF constitutes a new STR that includes an unboosted integrase strand transfer inhibitor with a high barrier against resistance with TAF and FTC. Its virological efficacy was non-inferior to dolutegravir-based regimens previously recommended by most guidelines for treatment initiation in large double-blind, randomised clinical trials in treatment-naïve or switch patients over 96 weeks. Tolerability and pharmacological properties of the regimen make it a useful tool to address several of the clinical management issues raised above.

Cardiovascular disease and diabetes in HIV-positive and HIV-negative gay and bisexual men over the age of 55 years in Australia: insights from the Australian Positive & Peers Longevity Evaluation Study.

OBJECTIVES: As HIV-positive people age, diagnosis and management of comorbidities associated with ageing are of increasing concern. In this study, we aimed to compare the self-reported prevalences of heart disease, stroke, thrombosis and diabetes in older Australian HIV-positive and HIV-negative gay and bisexual men (GBM). METHODS: We analysed data from the Australian Positive & Peers Longevity Evaluation Study (APPLES), a study of a prospectively recruited cross-sectional sample of 228 (51.1%) HIV-positive and 218 (48.9%) HIV-negative GBM, aged ≥ 55 years. Regression methods were used to assess the association of HIV status with self-reported comorbidities. RESULTS: Of 446 patients, 389 [200 (51.4%) HIV-positive] reported their disease history. The reported prevalence of comorbidities was higher in the HIV-positive group than in the HIV-negative group: heart disease, 19.5 versus 12.2%; stroke, 7.5 versus 4.2%; thrombosis, 10.5 versus 4.2%; and diabetes, 15.0 versus 9.0%, respectively. In adjusted analyses, HIV-positive GBM had significantly increased odds of reporting heart disease [adjusted odds ratio (aOR) 1.99; P = 0.03] and thrombosis (aOR 2.87; P = 0.01). In our analysis, HIV status was not significantly associated with either age at diagnosis of heart disease (median 53 years for HIV-positive GBM versus 55 years for HIV-negative GBM; P = 0.64) or 5-year cardiovascular disease (CVD) risk estimated using the Framingham risk score. CONCLUSIONS: HIV-positive GBM more commonly reported heart disease and thrombosis compared with their HIV-negative peers. These results further highlight the need to understand the impact of HIV on age-related comorbidities in GBM, to guide optimal screening and treatment strategies to reduce the risk of these comorbidities among the HIV-positive population.

Prevalence of HIV indicator conditions in late presenting patients with HIV: a missed opportunity for diagnosis?

AIM: To evaluate prior prevalence of HIV indicator conditions in late-presenters with HIV infection. DESIGN: Retrospective cohort study between 2000 and 2014 in a healthcare network in Melbourne, Australia comparing patients presenting with late diagnosis of HIV infection (CD4 < 350 cells/ml) to those patients who had a CD greater than or equal to 350 cells/ml at presentation. METHOD: The European AIDS Clinical Society guidelines on HIV indicator guided testing were used to assess for any indicator conditions in their prior medical history which may have represented a missed opportunity for earlier diagnosis. Main outcome measures: Descriptive statistics and prevalence of HIV indicator conditions. RESULTS: Of 436 patients with HIV infection, 82 were late presenters. Late presenters were more commonly male (83% vs. 75%, P = 0.11), older (mean age 45 vs. 39 years), born overseas (61% vs. 58%, P = 0.68) and report heterosexual transmission as their exposure risk (51% vs. 31%, P < 0.001). Of 80 patients with late presentation of HIV infection, 54 (55%) had at least one, 29 (36%) at least 2, 12 (15%) at least 3 and 5 (6%) had 4 or more previous HIV indicator conditions which would have triggered HIV testing according to guidelines. The most common indicator conditions were: unexplained loss of weight (31%), herpes zoster (10%), thrombocytopenia or leukopenia (10%), oral or oesophageal candidiasis (10%) and community acquired pneumonia (9%). Twenty patients (25%) had HIV indicator conditions diagnosed at least 12 months before the eventual diagnosis of HIV infection. DISCUSSION/ CONCLUSION: Patients diagnosed with late-presenting HIV often had an HIV indicator condition prior to presentation, presenting a missed opportunity for earlier diagnosis.

HIV in practice: current approaches and challenges in the diagnosis, treatment and management of HIV infection in Australia.

As treatment improves, people living with HIV (PLWHIV) can now expect to live longer, which means that the foci of HIV-related care for them and their medical practitioners continue to change. With an increasingly older cohort of patients with HIV infection, practitioners' key considerations are shifting from issues of acute treatment and patient survival to multiple comorbidities, toxicities associated with chronic therapy, and ongoing health maintenance. Within this context, this paper explores the current standard of practice for the management of HIV infection in Australia. We surveyed 56 Australian practitioners currently involved in managing HIV infection: 'HIV section 100' (HIV therapy-prescribing) general practitioners (s100 GPs; n = 26), sexual health physicians (SHPs; n = 24) and hospital-based physicians (HBPs; n = 6). Survey results for practice approaches and challenges were broadly consistent across the three practitioner specialties, apart from a few key areas. s100 GPs reported less prophylaxis use among patients whom they deemed at risk of HIV infection in comparison with SHPs, which may reflect differences in patient populations. Further, a higher proportion of s100 GPs nominated older HIV treatment regimens as their preferred therapy choices compared with the other specialties. In contrast with SHPs, s100 GPs were less likely to switch HIV therapies to simplify the treatment protocol, and to immediately initiate treatment upon patient request in those newly diagnosed with HIV infection. Considerably lower levels of satisfaction with current HIV practice guidelines were also reported by s100 GPs. It appears that greater support for s100 GPs may be needed to address these identified challenges and enhance approaches to HIV practice. Across all specialties, increasing access to mental health services for patients with HIV infection was reported as a key management issue. A renewed focus on providing improved mental health and wellbeing supports is recommended, particularly in the face of an ageing HIV-infected population.

Week 96 results of the randomized, multicentre Maraviroc Switch (MARCH) study.

OBJECTIVES: The Maraviroc Switch (MARCH) study week 48 data demonstrated that maraviroc, a chemokine receptor-5 (CCR5) inhibitor, was a safe and effective switch for the ritonavir-boosted protease inhibitor (PI/r) component of a two nucleos(t)ide reverse transcriptase inhibitor [N(t)RTI] plus PI/r-based antiretroviral regimen in patients with R5-tropic virus. Here we report the durability of this finding. METHODS: MARCH, an international, multicentre, randomized, 96-week open-label switch study, enrolled HIV-1-infected adults with R5-tropic virus who were stable (> 24 weeks) and virologically suppressed [plasma viral load (pVL) < 50 HIV-1 RNA copies/mL]. Participants were randomized to continue their current PI/r-based regimen (PI/r) or to switch to MVC plus two N(t)RTIs (MVC) (1:2 randomization). The primary endpoint was the difference in the proportion with pVL < 200 copies/mL at 96 weeks. The switch arm was defined as noninferior if the lower limit of the 95% confidence interval (CI) for the difference was < -12% in the intention-to-treat (ITT) population. Safety endpoints (the difference in the mean change from baseline or a comparison of proportions) were analysed as key secondary endpoints. RESULTS: Eighty-two (PI/r) and 156 (MVC) participants were randomized and included in the ITT analysis; 71 (87%) and 130 (83%) were in follow-up and on therapy at week 96. At week 96, 89.0% and 90.4% in the PI/r and MVC arms, respectively, had pVL < 50 copies/mL (95% CI -6.6, 10.2). Moreover, in those switching away from PI/r, there were significant reductions in mean total cholesterol (differences 0.31 mmol/L; P = 0.02) and triglycerides (difference 0.44 mmol/L; P < 0.001). Changes in CD4 T-cell count, renal function, and serious and nonserious adverse events were similar in the two arms. CONCLUSIONS: MVC as a switch for a PI/r is safe and effective at maintaining virological suppression while having significant lipid benefits over 96 weeks.

Low rates of endocarditis in healthcare-associated Staphylococcus aureus bacteremia suggest that echocardiography might not always be required.

Healthcare-associated Staphylococcus aureus bacteremia (HA-SAB) is an increasingly frequently observed complication of medical treatment. Current guidelines recommend evaluation with echocardiography and preferably transesophageal echocardiography for the exclusion of infectious endocarditis (IE). We performed a retrospective analysis of all patients with HA-SAB between 1 January 2007 and 31 July 2012. Patients were divided into those with a high degree of clinical suspicion of IE (prosthetic intracardiac device, hemodialysis or positive blood cultures for 4 days or more) or those with a low degree of clinical suspicion of IE (absence of high-risk features based on previous literature as strong indicators of endocarditis). Three hundred and fifty-eight patients with HA-SAB were evaluated to determine the prevalence of IE, including 298 (83 %) who had echocardiography. Fourteen patients (4 %) had a final diagnosis of IE after echocardiography. In the group with a high degree of clinical suspicion 11 out of 84 patients (13 %) had IE. In the group with a low degree of clinical suspicion group 3 out 274 patients (1.1 %) had IE. HA-SAB has a low rate of IE, especially in the absence of high-risk features such as prolonged bacteremia, intracardiac prosthetic devices, and hemodialysis. Echocardiographic imaging in this low-risk population of patients is rarely helpful and may generally be avoided, although careful clinical follow-up is warranted. Patients with HA-SAB who have mechanical valves, intracardiac devices, prolonged bacteremia or dialysis dependency have a high incidence of IE and should be evaluated thoroughly using echocardiography.

International travel in the immunocompromised patient: a cross-sectional survey of travel advice in 254 consecutive patients.

AIMS: Our primary aim was to determine the rate of overseas travel in immunocompromised individuals attending appropriate clinics at an Australian tertiary care hospital. We also aimed to characterise health-seeking behaviour prior to travel and investigated sources of pre-travel advice, compared travel patterns and activities between three specific immunosuppressed groups, and examined pre-immunosuppression patient serology. METHODS: We implemented a cross-sectional survey of patients between February and August 2012. This survey was implemented among three outpatient populations at Monash Medical Centre, an Australian tertiary care hospital. RESULTS: We recruited 254 immunosuppressed adults from three patient populations: human immunodeficiency virus-positive individuals, renal transplant patients and rheumatology patients requiring immunosuppressive therapy. No clinical intervention was performed. In the 10 years preceding the survey, 153 (60.2%) participants reported international travel. Of these, 105 (68.6%) were immunosuppressed at the time of travel. These patients were 47.6% male and 60% Australian born. Forty per cent were visiting friends and relatives as part of their travel. Fifty-four per cent of those immunocompromised at the time of travel were going to high-risk destinations. Pathology files indicated that serological screening was frequently not performed prior to immunosuppression in the renal transplant and rheumatology groups. CONCLUSIONS: Immunocompromised patients often travel to high-risk destinations with limited or inadequate pre-travel preparations. Doctors caring for the immunocompromised should be aware of travel risks, suitable vaccination protocols and when to refer to specialist travel clinics.

The significance of low-level viraemia in diverse settings: analysis of the Treat Asia HIV Observational Database (TAHOD) and the Australian HIV Observational Database (AHOD).

OBJECTIVES: The aim of the study was to assess the significance of low-level viraemia (LLV) and the timing of treatment change in low/middle-income country (L/MIC) compared with high-income country (HIC) settings. METHODS: Patients with virological control following commencement of combination antiretroviral therapy (cART) were included in the study. LLV was defined as undetectable viral load (<50 HIV-1 RNA copies/mL) followed by confirmed detectable viral load < 1000 copies/mL. Virological failure was defined as viral load > 1000 copies/mL. Kaplan-Meier plots of time to virological failure by prior LLV and income category were generated. Regimen changes in the setting of LLV were compared between sites. Sensitivity analysis of rates of LLV and virological failure by person-years and number of tests was conducted for differing definitions of LLV and virological failure. RESULTS: A total of 1748 patients from HICs and 823 patients from L/MICs were included in the study. One hundred and ninety-six (11.2%) HIC participants and 36 (4.4%) L/MIC participants experienced at least one episode of LLV. Of the patients who underwent regimen switch in HIC settings, the majority changed from a nucleoside reverse transcriptase inhibitor (NRTI)/protease inhibitor (PI) regimen to an NRTI/nonnucleoside reverse transcriptase inhibitor (NNRTI) regimen (26.8%). Very few switches were made in L/MIC settings. Rates of LLV were significantly higher for HICs compared with L/MICs per 1000 person-years (28.6 and 9.9 per 1000 person-years, respectively), but not in terms of the number of tests (9.4 and 7.2 per 1000 tests, respectively). Rates of virological failure per test were significantly higher for L/MICs compared with HICs (30.7 vs. 19.6 per 1000 tests, respectively; P < 0.001). LLV was a significant predictor of virological failure at 2 years in L/MICs [0.25; 95% confidence interval (CI) 0.11-0.50; P = 0.043] but not in HICs (0.13; 95% CI 0.08-0.22; P = 0.523). CONCLUSIONS: LLV is weakly predictive of virological failure at 2 years in L/MICs but not in HICs. This suggests that interventions targeted at subjects with LLV in L/MICs would help to improve treatment outcomes.

Cancer, immunodeficiency and antiretroviral treatment: results from the Australian HIV Observational Database (AHOD).

OBJECTIVES: The objective of the study was to conduct a within-cohort assessment of risk factors for incident AIDS-defining cancers (ADCs) and non-ADCs (NADCs) within the Australian HIV Observational Database (AHOD). METHODS: A total of 2181 AHOD registrants were linked to the National AIDS Registry/National HIV Database (NAR/NHD) and the Australian Cancer Registry to identify those with a notified cancer diagnosis. Included in the current analyses were cancers diagnosed after HIV infection. Risk factors for cancers were also assessed using logistic regression methods. RESULTS: One hundred and thirty-nine cancer cases were diagnosed after HIV infection among 129 patients. More than half the diagnoses (n = 68; 60%) were ADCs, of which 69% were Kaposi's sarcoma and 31% non-Hodgkin's lymphoma. Among the NADCs, the most common cancers were melanoma (n = 10), lung cancer (n = 6), Hodgkin's lymphoma (n = 5) and anal cancer (n = 5). Over a total of 21021 person-years (PY) of follow-up since HIV diagnosis, the overall crude cancer incidence rate for any cancer was 5.09/1000 PY. The overall rate of cancers decreased from 15.9/1000 PY [95% confidence interval (CI) 9.25-25.40/1000 PY] for CD4 counts < 100 cells/µL to 2.4/1000 PY (95% CI 1.62-3.39/1000 PY) for CD4 counts > 350 cells/µL. Lower CD4 cell count and prior AIDS diagnoses were significant predictors for both ADCs and NADCs. CONCLUSIONS: ADCs remain the predominant cancers in this population, although NADC rates have increased in the more recent time period. Immune deficiency is a risk factor for both ADCs and NADCs.

Visiting friends and relatives may be a risk for non-adherence for HIV-positive travellers.

We report three cases of immigrants to Australia, living with HIV/AIDS, who, while travelling in countries of origin or migration, were unable to continue to take their antiretrovirals appropriately. We discuss the possible reasons for this and ways to reduce the possibility of it happening. Travel may be a significant risk factor for non-adherence; pre-travel advice and planning might help to prevent it occurring.

Shooting at the DARC: potential issues with species-specific antimalarials.

Scientific drug design enables the production of novel agents that may be specific for individual malaria species, particularly by targeting their methods of cellular entry. Though there are practical and theoretical barriers to introducing novel agents into clinical practice, there may also be theoretical benefits to encourage further investigation of such agents, including a reduction in the rate of development of falciparum resistance. This paper discusses the potential risks and benefits such agents using the example of CCR5 blockers, drugs which are already in use for HIV treatment, but may be able to block DARC, the site of Plasmodium vivax into the human red blood cell.

New HIV diagnosis after occupational exposure screening: the importance of reporting needlestick injuries.

We describe three new diagnosis of HIV infection as a direct result of testing following occupational exposures (NSIs) in a low-prevalence setting. In each case the finding was unexpected. Our series provides a reminder of the importance of prompt reporting of NSIs by healthcare workers, access to rapid HIV testing and post-exposure prophylaxis with antiretrovirals to prevent transmission.

Rat bite fever as a presenting illness in a patient with AIDS.

The etiology of culture-negative septic arthritis is poorly characterised in persons infected with human immunodeficiency virus (HIV). New molecular methods may assist in the investigation of culture-negative infections of sterile sites, including septic arthritis. We describe the first case of septic arthritis due to the cause of rat bite fever (RBF), Streptobacillus moniliformis, confirmed by 16S rRNA sequence analysis, in a patient with newly diagnosed HIV infection.

Incidence and seroprevalence of dengue virus infections in Australian travellers to Asia.

The purpose of this study was to estimate the incidence density and prevalence of dengue virus infection in Australian travellers to Asia. We conducted a multi-centre prospective cohort study of Australian travellers over a 32-month period. We recruited 467 travellers (≥ 16 years of age) from three travel clinics who intended to travel Asia, and 387 (82.9%) of those travellers completed questionnaires and provide samples pre- and post-travel for serological testing for dengue virus infection. Demographic data, destination countries and history of vaccinations and flavivirus infections were obtained. Serological testing for dengue IgG and IgM by enzyme-linked immunosorbent assay (ELISA) (PanBio assay) was performed. Acute seroconversion for dengue infection was demonstrated in 1.0% of travellers, representing an incidence of 3.4 infections per 10,000 days of travel (95% confidence interval [CI]: 0.9-8.7). The seroprevalence of dengue infection was 4.4% and a greater number of prior trips to Asia was a predictor for dengue seroprevalence (p = 0.019). All travellers experienced subclinical dengue infections and had travelled to India (n = 3) and China (n = 1). This significant attack rate of dengue infection can be used to advise prospective travellers to dengue-endemic countries.

Southeast Asian ovalocytosis is associated with increased expression of Duffy antigen receptor for chemokines (DARC).

The Duffy antigen receptor for chemokines (DARC or Fy glycoprotein) carries antigens that are important in blood transfusion and is the main receptor used by Plasmodium vivax to invade reticulocytes. Southeast Asian ovalocytosis (SAO) results from an alteration in RBC membrane protein band 3 and is thought to mitigate susceptibility to falciparum malaria. Expression of some RBC antigens is suppressed by SAO, and we hypothesized that SAO may also reduce Fy expression, potentiallyleading to reduced susceptibility to vivax malaria. Blood samples were collected from individuals living in the Madang Province of Papua New Guinea. Samples were assayed using a flow cytometry assay for expression of Fy on the surface of RBC and reticulocytes by measuring the attachment of a phycoerythrin-labeled Fy6 antibody. Reticulocytes were detected using thiazole orange. The presence of the SAO mutation was confirmed by PCR. There was a small (approximately 10%) but statistically significant (p=0.049, Mann-Whitney U test) increase in Fy expression on SAO RBC compared with RBC from individuals without this polymorphism: mean Fy expression (mean fluorescence intensity [MFI]) was 10.12 +/- 1.22 for SAO heterozygotes versus an MFI of 8.95 +/- 1.1 for individuals without SAO. For reticulocytes the MFI values were 27.61 +/- 19.12 for SAO heterozygotes and 16.47 +/- 3.81 for controls. SAO is associated with increased and not decreased Fy6 expression so that susceptibility to P. vivax infection is unlikely to be affected.

Duffy antigen expression on reticulocytes does not alter following blood loss in an autologous donation model.

BACKGROUND: The Duffy blood group (Fy) antigen functions as the receptor whereby the malarial parasite Plasmodium vivax invades reticulocytes. In this study, we evaluated an autologous blood donation model to measure Fy expression during the anticipated response to blood loss. AIMS: This study aims to examine Fy expression following anticipated reticulocytosis in response to blood loss from autologous whole blood donation. METHOD: Subjects were healthy blood donors presenting for planned collection of two or three autologous units. Whole blood (450 ml +/- 10%) was collected and processed. Blood samples for Fy testing were obtained from the donations. These were assayed by flow cytometry by measuring binding of a phycoerythrin-labelled anti-Fy6 antibody and compared against reticulocyte numbers. Reticulocyte numbers were measured using thiazole orange. Results were compared from baseline (first donation) with samples at second and, if available, third, donations. Phenotyping for Fy a and b antigens was performed. RESULTS: Reticulocytes increased by a mean of 37% over baseline [0.93% (range 0.31-1.93) to 1.23% (0.32-3.51%)] following donation of two (n = 32) or three (n = 9) autologous whole blood units. Absolute reticulocyte count remained low. Mean and median Fy expression on mature red blood cells and reticulocytes did not change from baseline levels despite individual variation. No apparent relationship to serologically determined Fy a and/or b antigen status was present. CONCLUSION: Baseline expression of Fy antigen on mature red blood cells and reticulocytes is quite variable between individuals, but appears not to be greatly affected by mild to moderate reticulocytosis following blood loss in an autologous blood donation model.

Guidelines for the prevention of sepsis in asplenic and hyposplenic patients.

Asplenic or hyposplenic patients are at risk of fulminant sepsis. This entity has a mortality of up to 50%. The spectrum of causative organisms is evolving as are recommended preventive strategies, which include education, prophylactic and standby antibiotics, preventive immunizations, optimal antimalarial advice when visiting endemic countries and early management of animal bites. However, there is evidence that adherence to these strategies is poor. Consensus-updated guidelines have been developed to help Australian and New Zealand clinicians and patients in the prevention of sepsis in asplenic and hyposplenic patients.