High levels of engagement with testing for HIV and sexually transmissible infection among gay Asian men in Sydney and Melbourne: an observational study.

Background Gay and other men who have sex with men of Asian background (GAM) have been identified as a key population in efforts to eradicate HIV in New South Wales. The aims of the present study were to evaluate current levels of engagement with HIV and sexually transmissible infection (STI) testing services, assess knowledge of pre- and post-exposure prophylaxis and to identify factors associated with service engagement in this group. METHODS: A survey of 604 GAM residing in Sydney and Melbourne was undertaken. RESULTS: The data identified that a significant proportion of non-HIV-positive men (i.e. HIV-negative men and men whose HIV status was unknown) surveyed (n = 567; 93.9%) had engaged in frequent HIV testing and comprehensive STI testing in the 12 months prior to the survey (n = 180; 31.7%). There were significant differences (P < 0.05) in sexual practices at the bivariate level between those who reported frequent and comprehensive HIV/STI testing and those who did not. Those who tested regularly were substantially more sexually active, were more likely to have multiple partners (P = 0.001) and were more likely to engage in condomless anal intercourse with both casual (P < 0.001) and regular (P = 0.002) partners. Those who engaged with testing initiatives were more likely to discuss HIV status with both regular (P = 0.008) and casual (P < 0.001) partners, and identified more reasons to test than their counterparts (P < 0.001). The data also highlighted key service venues, with gay men most likely to have used public sexual health clinics (46.9%) as their most recent testing venue. CONCLUSIONS: The data demonstrate an association between high levels of male-to-male sexual activity and engagement in frequent and comprehensive HIV and STI testing. This likely derives from both self-perceived notions of risk and current reliance on established gay community organisations to convey information around testing. Increasing engagement with testing initiatives beyond GAM who self-identify as being at high HIV and STI risk will require the use of novel routes by which to disseminate this information.

Challenging historical perspectives of the 24-h chemotherapy day: Flexible chemotherapy dose-timing guidelines.

AIM: Variation in dose-timing within multiday chemotherapy regimens is largely unknown with convention being to administer subsequent days of treatment at 24-h intervals. However, in reality there are many occasions where doses are given either earlier or later to accommodate a variety of clinical and operational priorities. This project aimed to evaluate the degree of existing variation in chemotherapy dose-timing and to investigate whether deliberate variation could improve quality and efficiency outcomes such as reduction of after hours chemotherapy administration or reduced inpatient length of stay. METHOD: Chemotherapy charts and hospital admission datasets (n = 112) from sarcoma and hematology inpatient regimens were retrospectively audited to ascertain existing variation in dose-timing and overall length of stay. Clinical practice guidelines enabling a safe degree of dose-timing variation for individual chemotherapy regimens were developed, implemented over a 3-month period, and evaluated against safety, efficiency and economic outcomes. RESULTS: Baseline dose-timing variation was common with administration occurring up to 8 h early and 7 h later than conventional 24-h dosing intervals. Following implementation of clinical practice guidelines, there was a 10% reduction in chemotherapy finishing after hours and a significant reduction in length of stay for two sarcoma regimens, projected to save 24 inpatient bed days (over $20,000) across more than forty inpatient episodes annually. CONCLUSION: Deviation from the standard 24-h chemotherapy day (deliberately or inadvertently) was a common yet unstandardized practice. Clinical practice guidelines enabling flexible dose-timing of chemotherapy provided an opportunity to improve chemotherapy administration safety measures, tailor chemotherapy delivery to ward and patient needs, and in some instances reduce non-value-added length of stay.

Quantification of plasma HIV RNA using chemically engineered peptide nucleic acids.

The remarkable stability of peptide nucleic acids (PNAs) towards enzymatic degradation makes this class of molecules ideal to develop as part of a diagnostic device. Here we report the development of chemically engineered PNAs for the quantitative detection of HIV RNA at clinically relevant levels that are competitive with current PCR-based assays. Using a sandwich hybridization approach, chemical groups were systematically introduced into a surface PNA probe and a reporter PNA probe to achieve quantitative detection for HIV RNA as low as 20 copies per millilitre of plasma. For the surface PNA probe, four cyclopentane groups were incorporated to promote stronger binding to the target HIV RNA compared with PNA without the cyclopentanes. For the reporter PNA probe, 25 biotin groups were attached to promote strong signal amplification after binding to the target HIV RNA. These general approaches to engineer PNA probes may be used to detect other RNA target sequences.

Broadly neutralizing antibodies suppress HIV in the persistent viral reservoir.

Several highly potent and broadly neutralizing monoclonal antibodies against HIV have recently been isolated from B cells of infected individuals. However, the effects of these antibodies on the persistent viral reservoirs in HIV-infected individuals receiving antiretroviral therapy (ART) are unknown. We show that several HIV-specific monoclonal antibodies--in particular, PGT121, VRC01, and VRC03--potently inhibited entry into CD4(+) T cells of HIV isolated from the latent viral reservoir of infected individuals whose plasma viremia was well controlled by ART. In addition, we demonstrate that HIV replication in autologous CD4(+) T cells derived from infected individuals receiving ART was profoundly suppressed by three aforementioned and other HIV-specific monoclonal antibodies. These findings have implications for passive immunotherapy as an approach toward controlling plasma viral rebound in patients whose ART is withdrawn.

Developing a performance data suite to facilitate lean improvement in a chemotherapy day unit.

PURPOSE: A multidisciplinary team from the Peter MacCallum Cancer Centre in Melbourne, Australia, developed a performance data suite to support a service improvement project based on lean manufacturing principles in its 19-chair chemotherapy day unit (CDU) and cytosuite chemotherapy production facility. The aims of the project were to reduce patient wait time and improve equity of access to the CDU. METHODS: A project team consisting of a pharmacist and CDU nurse supported the management team for 10 months in engaging staff and customers to identify waste in processes, analyze root causes, eliminate non-value-adding steps, reduce variation, and level workloads to improve quality and flow. Process mapping, staff and patient tracking and opinion surveys, medical record audits, and interrogation of electronic treatment records were undertaken. RESULTS: This project delivered a 38% reduction in median wait time on the day (from 32 to 20 minutes; P < .01), 7-day reduction in time to commencement of treatment for patients receiving combined chemoradiotherapy regimens (from 25 to 18 days; P < .01), and 22% reduction in wastage associated with expired drug and pharmacy rework (from 29% to 7%; P < .01). Improvements in efficiency enabled the cytosuite to increase the percentage of product manufactured within 10 minutes of appointment times by 29% (from 47% to 76%; P < .01). CONCLUSION: A lean improvement methodology provided a robust framework for improved understanding and management of complex system constraints within a CDU, resulting in improved access to treatment and reduced waiting times on the day.

Challenges in detecting HIV persistence during potentially curative interventions: a study of the Berlin patient.

There is intense interest in developing curative interventions for HIV. How such a cure will be quantified and defined is not known. We applied a series of measurements of HIV persistence to the study of an HIV-infected adult who has exhibited evidence of cure after allogeneic hematopoietic stem cell transplant from a homozygous CCR5Δ32 donor. Samples from blood, spinal fluid, lymph node, and gut were analyzed in multiple laboratories using different approaches. No HIV DNA or RNA was detected in peripheral blood mononuclear cells (PBMC), spinal fluid, lymph node, or terminal ileum, and no replication-competent virus could be cultured from PBMCs. However, HIV RNA was detected in plasma (2 laboratories) and HIV DNA was detected in the rectum (1 laboratory) at levels considerably lower than those expected in ART-suppressed patients. It was not possible to obtain sequence data from plasma or gut, while an X4 sequence from PBMC did not match the pre-transplant sequence. HIV antibody levels were readily detectable but declined over time; T cell responses were largely absent. The occasional, low-level PCR signals raise the possibility that some HIV nucleic acid might persist, although they could also be false positives. Since HIV levels in well-treated individuals are near the limits of detection of current assays, more sensitive assays need to be developed and validated. The absence of recrudescent HIV replication and waning HIV-specific immune responses five years after withdrawal of treatment provide proof of a clinical cure.

Paucity of HIV DNA methylation in latently infected, resting CD4+ T cells from infected individuals receiving antiretroviral therapy.

Maintenance of HIV latency in vitro has been linked to methylation of HIV DNA. However, examinations of the degree of methylation of HIV DNA in the latently infected, resting CD4(+) T cells of infected individuals receiving antiretroviral therapy have been limited. Here, we show that methylation of the HIV 5' long terminal repeat (LTR) in the latent viral reservoir of HIV-infected aviremic individuals receiving therapy is rare, suggesting that other mechanisms are likely involved in the persistence of viral latency.

Relationship between residual plasma viremia and the size of HIV proviral DNA reservoirs in infected individuals receiving effective antiretroviral therapy.

Residual plasma viremia (<50 copies/mL) persists in certain human immunodeficiency virus (HIV)-infected individuals receiving antiretroviral therapy (ART); however, the relationship between the degree of residual plasma viremia, the size of HIV reservoirs, and the level of immune activation has not been delineated. Here, we demonstrate that residual plasma viremia correlates with the size of the CD4(+) T cell viral reservoir, but not with markers of immune activation, suggesting that reactivation of the latent viral reservoir may not be the sole source of residual plasma viremia. Novel therapeutic strategies aimed at targeting the source of residual viremia may be necessary to achieve viral eradication.