Appropriate usage of post-exposure prophylaxis-in-pocket for HIV prevention by individuals with low-frequency exposures.

PEP-In-Pocket (Post-Exposure Prophylaxis-In-Pocket, or "PIP") is a biobehavioural HIV prevention strategy wherein patients are proactively identified and given a prescription for HIV post-exposure prophylaxis (PEP) medications to self-initiate in case of high-risk exposures. We evaluated this strategy in a prospective observational study at two hospital-based clinics in Toronto, Canada. HIV-negative adults using PIP underwent chart review and completed quarterly electronic questionnaires over 12 months. The primary objective was to quantify appropriate PIP initiation, defined as starting PIP within 72 h of a high-risk exposure. Secondary objectives were to quantify HIV seroconversions, changes in sexual risk behaviour, sexual satisfaction, and satisfaction with the PIP strategy. From 11/2017 to 02/2020, 43 participants enrolled and completed ≥1 questionnaire. PIP was self-initiated on 27 occasions by 15 participants, of which 24 uses (89%) were appropriate, 2 were unnecessary, and 1 was for an unknown exposure. Chart review identified no inappropriate non-use. Over 32 person-years of testing follow-up, we observed zero HIV seroconversions. Sexual risk declined modestly over follow-up, with a HIRI-MSM (HIV Incidence Risk Index for MSM) change of -0.39 (95% CI = -0.58, -0.21 per 3 months, p < .001). Sexual satisfaction was stable over time. At 12 months, 31 (72%) remained on PIP, 8 (19%) had transitioned to pre-exposure prophylaxis and 4 (9%) were lost-to-follow-up. Among participants who remained on PIP and completed questionnaires at 12 months, 24/25 (96%) strongly/somewhat agreed that PIP decreased their anxiety about contracting HIV and 25/25 (100%) strongly/somewhat agreed that they would recommend PIP to a friend. PIP is a feasible HIV prevention strategy in carefully selected individuals at modest HIV risk.

Assessing the Potential for Nurse-Led HIV Pre- and Postexposure Prophylaxis in Ontario.

BACKGROUND AND PURPOSE: HIV prevention efforts in Ontario require increased implementation of strategies including post- and pre-exposure prophylaxis. Access to these interventions could be improved by their provision through nurse-led models of care. We assessed nurses' readiness to deliver these interventions using a behavioral change framework. METHODS: We distributed an online survey to nurses in every Ontario sexual health clinic, HIV clinic, and community health center between March-June 2018, to determine the level of support for nurse-led postexposure prophylaxis/pre-exposure prophylaxis; we also explored nurses' "capabilities," "opportunities," and "motivations" for providing postexposure prophylaxis/pre-exposure prophylaxis. RESULTS: Overall, 72.7% of respondents supported implementation of both nurse-led postexposure prophylaxis and pre-exposure prophylaxis. More experienced nurses were less likely to support nurse-led postexposure prophylaxis and pre-exposure prophylaxis (adjusted odds ratio = 0.55 per decade nursing, 95% confidence interval (0.37, 0.82)). Nurses reported a high degree of knowledge of topics related to postexposure prophylaxis/pre-exposure prophylaxis, with the exception of creatinine interpretation. CONCLUSIONS: Ontario nurses report high levels of support for nurse-led postexposure prophylaxis and pre-exposure prophylaxis and are well positioned to provide these interventions. Targeted education and implementation efforts are needed to engage these nurses in postexposure prophylaxis and pre-exposure prophylaxis delivery.

HIV postexposure prophylaxis-in-pocket: long-term follow-up of individuals with low-frequency, high-risk HIV exposures.

BACKGROUND: HIV preexposure prophylaxis and postexposure prophylaxis are two major biomedical HIV prevention modalities. The utility of these prevention tools for individuals with infrequent high-risk HIV exposures remains uncertain. HIV postexposure prophylaxis-in-pocket ('PIP') may be an effective HIV prevention tool in such situations. Here, we present long-term follow-up of a cohort of patients initiated on PIP for HIV prevention. METHODS: We retrospectively evaluated clinical characteristics of patients initiated on PIP as a primary HIV prevention tool between 1 January 2016 to 31 May 2019 at the Toronto General Hospital HIV Prevention Clinic and St. Michael's Hospital HIV Clinic, both in Toronto, Canada. Patients were referred for consideration of a biomedical HIV prevention modality. Individuals with a low frequency of high-risk exposures to HIV were initiated on PIP after counselling, and were followed at regular intervals. Demographic and clinical data was collected with a standardized form. RESULTS: In total, 79 patients were initiated on PIP as a primary HIV prevention modality and followed for a mean duration of 14.8 months combining for a total of 97.3 patient-years. Twenty-one (26.6%) patients used their PIP, and 32 courses of PIP were taken during the study period. Transitions between HIV prevention modalities included 13 (16.5%) patients who transitioned from PrEP to PIP, and 22 (27.8%) patients who transitioned from PIP to PrEP. No HIV seroconversions were detected during the course of this study. CONCLUSION: PIP is helpful HIV prevention modality for individuals with a low frequency of high-risk HIV exposures.

Cardiovascular risk management in rheumatoid arthritis: A large gap to close.

OBJECTIVE: Rheumatoid arthritis (RA) portends significant cardiovascular morbidity and mortality. We therefore determined how often rheumatologists screened for and managed cardiovascular risk factors in RA patients, and the barriers to doing so. METHODS: We examined 300 patient charts from 10 university-affiliated rheumatology practices, to ascertain if they had been screened, treated and/or referred over a 3-year period. We subsequently distributed a national survey to Canadian rheumatologists to elucidate challenges in performing optimal cardiovascular risk modification. RESULTS: Most patients were screened for hypertension. Forty-one per cent were found to be hypertensive; however, the majority of these patients were neither treated nor referred to another provider for management. A small minority of patients were screened for diabetes and/or hyperlipidaemia, and these were usually not addressed if abnormal. Men were referred more frequently than women. Consistent with these findings, the majority of rheumatologists from the national survey felt that they did not manage cardiovascular risk adequately; 79.4% cited a lack of time as a major barrier, and 82.5% felt that it should be managed by the primary care provider. CONCLUSION: There is marked underdiagnosis and undertreatment of cardiac risk in RA. Several major barriers exist, including lack of time. Most rheumatologists feel that this aspect of care is the responsibility of primary care physicians.

Therapy and pharmacological properties of hydroxychloroquine and chloroquine in treatment of systemic lupus erythematosus, rheumatoid arthritis and related diseases.

OBJECTIVES: This review examines the pharmacokinetics, modes of action and therapeutic properties of the anti-malarial drugs, hydroxychloroquine (HCQ) and chloroquine (CQ), in the treatment of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and related conditions, as well as osteoarthritis (OA). KEY FINDINGS: Both HCQ and CQ have historically been employed successfully for the treatment of SLE and RA for over 70 years. HCQ has been used extensively for SLE where it has a good reputation for controlling the dermatological complications in SLE. It has also been reported to effectively control the symptoms of Sjøgren's syndrome, as well as preventing thrombosis in phospholipid antibody (aPL) syndrome. In RA and SLE, HCQ is preferred because of the lower incidence of gastrointestinal adverse reactions compared with CQ and it might have a lower risk of ocular adverse reactions. There is increasing evidence that HCQ may reduce atherosclerosis and risks of cardiovascular disease in rheumatic patients. Both HCQ and CQ have been shown to improve glycaemia and reduce the risks of type II diabetes mellitus. Although both HCQ and CQ are effective in low-moderate RA, HCQ is now preferred as part of combination therapy for more severe disease. The advantages of combination therapy are that the doses of the individual drugs may be lowered so reducing adverse reactions. Both HCQ and CQ are diastereoisomers, have basic properties and are given as the sulphate and phosphate salts. While being relatively well absorbed orally and with good bioavailability, they have long and variable plasma terminal elimination half-lives (approximately 40-60 days). This reflects their high volume of distribution, V D (HCQ 44,000L; CQ 65,000L) which extends into aqueous compartments, long mean residence time (HCQ 1300 h; CQ 900 h) and with about half the drugs (metabolites) undergoing renal clearance. The strong binding to melanin reflects the ocular injury and dermatological properties of these drugs. The consensus is that the occurrence of ocular adverse reactions can be minimised by close attention to the dose (which should be set on a body weight basis) with regular (e.g. quarterly) retinal examination. Although HCQ and CQ can pass through the placenta, the use of these drugs during pregnancy does not appear to risk harm to the baby and might be beneficial to the mother with SLE and her child by controlling the SLE disease activity, which is known to be an important factor affecting pregnancy outcome. The modes of action of HCQ and CQ in these arthritides represent somewhat of an enigma. Undoubtedly, these drugs have multiple actions related, in part, their ability to accumulate in lysosomes and autophagosomes of phagocytic cells as well as affecting MHC Class II expression and antigen presentation; actions of the production of pro-inflammatory cytokines [e.g. interleukin-1 (IL-1) tumour necrosis factor-α (TNFα)]; control of toll-like receptor-9 activation; and leucocyte generation of reactive oxygen species (ROS); i.e. antioxidant activity. The actions of these drugs on T and B cells are less clear but may depend on these leucocyte-mediated actions. Anti-malarials also protect against cytokine-mediated cartilage resorption. This and other actions may underlie the potential benefits in treating OA. The exact relationships of these various actions, mostly determined in vitro, have not been specifically defined in vivo or ex vivo in relation to clinical efficacy. OUTCOMES: HCQ and CQ have a good reputation for being effective and relatively safe treatments in SLE, mild-moderate RA and Sjøgren's syndrome. There is need for (a) more information on their mode of action in relation to the control of these diseases, (b) scope for developing formulations that have improved pharmacokinetic and therapeutic properties and safety, and (c) further exploring their use in drug combinations not only with other disease modifying agents but also with biologics.