Experiences of Migrant People Living with HIV in a Multidisciplinary HIV Care Setting with Rapid B/F/TAF Initiation and Cost-Covered Treatment: The 'ASAP' Study.

This study aimed to explore the experiences of migrant people living with HIV (MLWH) enrolled in a Montreal-based multidisciplinary HIV care clinic with rapid antiretroviral treatment (ART) initiation and cost-covered ART. Between February 2020 and March 2022, 32 interviews were conducted with 16 MLWH at three time-points (16 after 1 week of ART initiation, 8 after 24 weeks, 8 after 48 weeks). Interviews were analyzed via the Framework Method. Thirty categories were identified, capturing experiences across the HIV care cascade. At diagnosis, most MLWH described "initially experiencing distress". At linkage, almost all MLWH discussed "navigating the health system with difficulty". At treatment initiation, almost all MLWH expressed "being satisfied with treatment", particularly due to a lack of side effects. Regarding care retention, all MLWH noted "facing psychosocial or health-related challenges beyond HIV". Regarding ART adherence, most MLWH expressed "being satisfied with treatment" with emphasis on their taking control of HIV. At viral suppression, MLWH mentioned "finding more peace of mind since becoming undetectable". Regarding their perceived health-related quality of life, most MLWH indicated "being helped by a supportive social network". Efficient, humanizing, and holistic approaches to care in a multidisciplinary setting, coupled with rapid and free ART initiation, seemed to help alleviate patients' concerns, address their bio-psycho-social challenges, encourage their initial and sustained engagement with HIV care and treatment, and ultimately contribute to positive experiences.

Barriers and facilitators related to HCV treatment uptake among HIV coinfected populations in Canada: Patient and treatment provider perceptions.

BACKGROUND: Direct-acting antiviral (DAA) uptake is challenging across HIV-hepatitis C (HCV) coinfected populations. This study sought to identify barriers and facilitators related to DAA uptake in priority populations in Canada. METHODS: This qualitative descriptive study included 11 people living with HIV with a history of HCV and 15 HCV care providers. Participants were part of either nominal groups (n = 4) or individual interviews (n = 6) in which they identified and ranked barriers and facilitators to DAA uptake. Consolidated lists of barriers and facilitators were identified thematically. RESULTS: Patient participants highly ranked the following barriers: competing priorities and needs (ie, social instability and mental health), delays in care, lack of adherence, and polypharmacy. Provider participant top barriers were the following: competing priorities and needs (ie, social chaos), delays in care (eg, systemic barriers, difficulties engaging patients, lack of trained HCV providers), and HCV-related stigma. Patient participants identified having a strong network of health care providers, family, and friends, possessing intrinsic motivation, and DAAs being a simple and tolerable oral treatment as important facilitators. Provider participant top-ranked facilitators were having resources to identify hard-to-reach populations (eg, patient navigation, outreach), holistic care and addiction management, provider HCV education, and a strong network of interprofessional collaboration. CONCLUSION: The barriers to DAA initiation addressed by patients and providers overlapped, with some nuances. Multidisciplinary care fostering a strong supportive network and intrinsically motivated patients along with HCV education emerged as key facilitators. This study provides insights for developing potential strategies to improve DAA uptake among HIV-HCV coinfected people in Canada.

Oral cannabinoids in people living with HIV on effective antiretroviral therapy: CTN PT028-study protocol for a pilot randomised trial to assess safety, tolerability and effect on immune activation.

INTRODUCTION: Despite antiretroviral therapy (ART), people living with HIV have higher rates of non-infectious chronic diseases. These conditions are driven by relatively high levels of inflammation persisting on ART compared with uninfected individuals. Chronic inflammation also contributes to HIV persistence during ART. Cannabis when taken orally may represent a way to reduce inflammation and strengthen immune responses. Before planning large interventional studies, it is important to ensure that cannabis taken orally is safe and well tolerated in people living with HIV. We propose to conduct a pilot randomised trial to examine the safety and tolerability of cannabis oils containing tetrahydrocannabinol (THC) and cannabidiol (CBD) consumed orally in people living with HIV. We will also measure inflammatory markers, markers of HIV persistence in peripheral blood cells and changes in the gastrointestinal microbiome. METHODS AND ANALYSIS: Twenty-six people living with HIV having undetectable viral load for at least 3 years will be randomised to receive TN-TC11LM (THC:CBD in 1:1 ratio) or TN-TC19LM (THC:CBD in 1:9 ratio) capsules daily for 12 weeks. Safety and tolerability of these capsules will be assessed through haematological, hepatic and renal blood tests, face-to-face interviews and questionnaires. Proportions of participants without any signs of significant toxicity (grades 0-2 scores on the WHO toxicity scale) and who complete the study, as well as scores on quality of life and mood will be examined using descriptive statistics. The effects on inflammatory markers, markers of peripheral blood reservoir size and effect on the composition of the gastrointestinal microbiome will be assessed before and after study completion. ETHICS AND DISSEMINATION: This study has been approved by the Research Institute of the McGill University Health Centre. A Data Safety Monitor will review safety information at regular intervals. The final manuscript will be submitted to an open-access journal within 6 months of study completion. TRIAL REGISTRATION NUMBER: NCT03550352.

A comparison of virological suppression and rebound between Indigenous and non-Indigenous persons initiating combination antiretroviral therapy in a multisite cohort of individuals living with HIV in Canada.

BACKGROUND: This study compared time to virological suppression and rebound between Indigenous and non-Indigenous individuals living with HIV in Canada initiating combination antiretroviral therapy (cART). METHODS: Data were from the Canadian Observational Cohort collaboration; eight studies of treatment-naive persons with HIV initiating cART after 1/1/2000. Fine and Gray models were used to estimate the effect of ethnicity on time to virological suppression (two consecutive viral loads [VLs] <50 copies/ml at least 3 months apart) after adjusting for the competing risk of death and time until virological rebound (two consecutive VLs >200 copies/ml at least 3 months apart) following suppression. RESULTS: Among 7,080 participants were 497 Indigenous persons of whom 413 (83%) were from British Columbia. The cumulative incidence of suppression 1 year after cART initiation was 54% for Indigenous persons, 77% for Caucasian and 80% for African, Caribbean or Black (ACB) persons. The cumulative incidence of rebound 1 year after suppression was 13% for Indigenous persons, 6% for Caucasian and 7% for ACB persons. Indigenous persons were less likely to achieve suppression than Caucasian participants (aHR=0.58, 95% CI 0.50, 0.68), but not more likely to experience rebound (aHR=1.03, 95% CI 0.84, 1.27) after adjusting for age, gender, injection drug use, men having sex with men status, province of residence, baseline VL and CD4+ T-cell count, antiretroviral class and year of cART initiation. CONCLUSIONS: Lower suppression rates among Indigenous persons suggest a need for targeted interventions to improve HIV health outcomes during the first year of treatment when suppression is usually achieved.

High level antibody avidity is achieved in HIV-seropositive recipients of an inactivated split adjuvanted (AS03A) influenza vaccine.

PURPOSE: More severe influenza disease and poor vaccine immunogenicity is reported in HIV-infected patients. We measured antibody avidity after influenza vaccination in HIV patients to assess vaccine efficacy. METHODS: Two dosing strategies (Group1: single dose, n = 28. Group2: single dose plus booster, n = 36) with an AS03A-adjuvanted H1N12009 pandemic influenza vaccine (Arepanrix, GSK) were assessed in HIV patients. Serum hemagglutination inhibition (HAI) titers and antibody avidity reported as an avidity index (AI) were measured at days 21 and 42 and at 6 months. RESULTS: Baseline HIV parameters were similar among all participants. Eighteen participants had measurable baseline HAI titers. In these subjects, AI was at ~9 at baseline and was not significantly increased by one or two vaccine doses. In those without detectable baseline antibodies, immunization induced modest antibody titers [Group1 HAI, 61 (26-144); Group2 HAI, 46 (28-76)] with high AI after one dose at day 21 [Group1 AI, 8.8 (7.3-10.7); Group2 AI, 8.9 (7.8-10.1)]. A second dose of vaccine generated significantly higher HAI titers at day 42 [Group1 HAI, 41 (18-90); Group2 HAI, 92 (64-132)] and persisted to 6 months [Group1 HAI, 9 (6-13); Group2 HAI, 19 (13-30)]. All subjects who produced detectable HAI titers after vaccination generated high antibody avidity (AI, 9-10), which persisted up to 6 months. CONCLUSION: In participants initially seronegative, two doses of vaccine enabled a greater percentage of subjects to respond to the vaccine and elicited higher HAI titers. All subjects who produced detectable HAI titers also rapidly generated high AI in the short and long term. We demonstrate that high avidity antibodies can be achieved after vaccination and support a two-dose immunization strategy for HIV-positive subjects.

Didanosine, interferon-alfa and ribavirin: a highly synergistic combination with potential activity against HIV-1 and hepatitis C virus.

OBJECTIVE: To evaluate the antiviral triple combination didanosine (ddI), interferon-alfa (IFN-alpha), and ribavirin for potential synergy in inhibition of HIV-1 replication in vitro. METHODS: Phytohaemagglutinin-stimulated cord blood mononuclear cells were infected with HIV-1(IIIB) or the HXB2D molecular clone of HIV-1 then cultured with interleukin-2 with ddI, ribavirin or IFN-alpha, alone and in combination. Reverse transcriptase activity was measured after 7 days to determine the inhibitory concentration of 50% (IC(50)) for the various drugs in replicate assays. Analysis of combined effects was performed using both the median effect principle (CalcuSyn, Biosoft) and three-dimensional modelling (MacSynergy II). RESULTS: The triple combination was highly synergistic against HIV-1 in vitro with combination indices < 1. The mean IC(50) was reduced from 6.85 to 0.90 micromol/l (P < 0.001) for ddI and from 6.58 to 1.00 micromol/l (P < 0.001) for IFN-alpha. No increased cytotoxicity was observed. Results were similar with both viral strains and using both analyses. In the triple combination, increasing concentrations of IFN-alpha resulted only a slight enhancement of synergy: synergy volumes were 134 [95% confidence limit (CL), 77-191] with 5 U IFN-alpha and 214.92 (95% CL, 116-314) with 10 U. This supporting the observation that the majority of the synergistic activity was derived from the combination of ddI and ribavirin, with IFN-alpha providing additional additive suppression. CONCLUSIONS: This novel triple combination has the potential to provide simultaneous activity against both HIV and hepatitis C and deserves further study to determine if can be safely administered in the clinical setting.