A two-day workshop reviewing Canadian provincial and national HIV care cascade indicators, reporting, challenges, and recommendations.

BACKGROUND: The HIV care cascade is an indicators-framework used to assess achievement of HIV clinical targets including HIV diagnosis, HIV care initiation and retention, initiation of antiretroviral therapy, and attainment of viral suppression for people living with HIV. METHODS: The HIV Care Cascade Research Development Team at the CIHR Canadian HIV Trials Network Clinical Care and Management Core hosted a two-day virtual workshop to present HIV care cascade data collected nationally from local and provincial clinical settings and national cohort studies. The article summarizes the workshop presentations including the indicators used and available findings and presents the discussed challenges and recommendations. RESULTS: Identified challenges included (1) inconsistent HIV care cascade indicator definitions, (2) variability between the use of nested UNAIDS's targets and HIV care cascade indicators, (3) variable analytic approaches based on differing data sources, (4) reporting difficulties in some regions due to a lack of integration across data platforms, (5) lack of robust data on the first stage of the care cascade at the sub-national level, and (6) inability to integrate key socio-demographic data to estimate population-specific care cascade shortfalls. CONCLUSION: There were four recommendations: standardization of HIV care cascade indicators and analyses, additional funding for HIV care cascade data collection, database maintenance and analyses at all levels, qualitative interviews and case studies characterizing the stories behind the care cascade findings, and employing targeted positive-action programs to increase engagement of key populations in each HIV care cascade stage.

HISTORIQUE: La cascade des soins du VIH est un cadre d'indicateurs utilisé pour évaluer l'atteinte des cibles cliniques du VIH, y compris le diagnostic, le début et le maintien des soins, le début du traitement antirétroviral et l'obtention de la suppression virale chez les personnes qui vivent avec le VIH. MÉTHODOLOGIE: L'équipe de développement de la recherche sur la cascade des soins du VIH située au noyau de perfectionnement de la gestion clinique du Réseau canadien pour les essais VIH des IRSC a organisé un atelier virtuel de deux jours pour présenter les données sur la cascade des soins du VIH amassées dans les milieux cliniques locaux et provinciaux et les études de cohorte de tout le pays. L'article résume les présentations d'ateliers, y compris les indicateurs utilisés et les observations disponibles, et présente les défis et recommandations abordés. RÉSULTATS: Les défis mis en évidence incluaient 1) les définitions hétérogènes des indicateurs de la cascade des soins sur le VIH, 2) la variabilité entre l'utilisation des cibles d'ONUSIDA imbriquées et les indicateurs de cascade des soins du VIH, 3) des approches analytiques variables d'après diverses sources de données, 4) la déclaration des difficultés dans certaines régions à cause de l'absence d'intégration entre les plateformes de données, 5) l'absence de données vigoureuses sur la première étape de la cascade des soins infranationaux et 6) l'incapacité d'intégrer les principales données sociodémographiques pour évaluer les écueils de la cascade des soins populationnels. CONCLUSION: Quatre recommandations ont été formulées : la standardisation des indicateurs et des analyses de la cascade des soins du VIH, le financement supplémentaire de la collecte de la cascade des soins du VIH, l'entretien des bases de données et les analyses à tous les échelons, les entrevues qualitatives et les études de cas qui caractérisent les histoires qui se cachent derrière les observations tirées de la cascade des soins et le recours à des programmes d'action positive ciblés pour accroître la participation de populations clés à chaque étape de la cascade des soins du VIH.

TIGIT blockade enhances NK cell activity against autologous HIV-1-infected CD4+ T cells.

OBJECTIVES: During chronic human immunodeficiency virus (HIV)-1 infection, inhibitory molecules upregulated on lymphocytes contribute to effector cell dysfunction and immune exhaustion. People living with HIV (PLWH) are at greater risk for age-related morbidities, an issue magnified by human cytomegalovirus (CMV) coinfection. As CMV infection modifies natural killer (NK) cell properties and NK cells contribute to protection against HIV-1 infection, we considered the role of T-cell immunoreceptor with immunoglobulin and intracellular tyrosine inhibitory motif domains (TIGIT) in NK cell-based HIV-1 immunotherapy and elimination strategies. METHODS: We measured TIGIT expression on immune cell subsets of 95 PLWH and assessed its impact on NK cell function, including elimination of autologous CD4+ T cells infected through reactivation of endogenous HIV-1. RESULTS: TIGIT was expressed on CD4+ T cells, CD8+ T cells and NK cells from PLWH. Although TIGIT levels on T cells correlated with HIV-1 disease progression, the extent of TIGIT expression on NK cells more closely paralleled adaptation to CMV. TIGIT interacts with its predominant ligand, poliovirus receptor (PVR), to inhibit effector cell functions. Circulating CD4+ T cells from PLWH more frequently expressed PVR than HIV-seronegative controls, and PVR expression was enriched in CD4+ T cells replicating HIV-1 ex vivo. Treatment with anti-TIGIT monoclonal antibodies increased NK cell HIV-1-specific antibody-dependent cytotoxicity in vitro and ex vivo. CONCLUSION: Blocking TIGIT may be an effective strategy to invigorate antibody-dependent NK cell activity against HIV-1 activated in cellular reservoirs for cure or treatment strategies.

Expanding access to HIV testing through Canadian community pharmacies: findings from the APPROACH study.

BACKGROUND: There is a need for acceptable and feasible HIV testing options to ensure people living with HIV know their status so they can access care. Pharmacist-provided HIV point-of-care testing (POCT) may overcome testing barriers, including privacy concerns, testing wait times, and improve accessibility. In the APPROACH study, we aimed to develop and assess an HIV POCT program in community pharmacies for future scale up and evaluation. This paper describes the program uptake, participant and pharmacist experiences, and implementation factors. METHODS: A pharmacist-provided HIV POCT program was offered in 4 pharmacies in two Canadian provinces. A mixed methods design incorporated self-report questionnaire data, participant telephone interviews, pharmacist focus groups, workload analysis, and situational analysis to assess the uptake, acceptability and feasibility of the HIV POCT program. RESULTS: Over the 6-month pilot, 123 HIV tests were performed. One new case of HIV was identified; this participant was linked with confirmatory testing and HIV care. Participants were predominantly male (76%), with a mean age of 35 years. This was the first HIV test for 27% participants, and 75% were at moderate to very high risk of undiagnosed HIV infection, by Denver HIV Risk Score. Questionnaires and telephone interviews showed participants were very satisfied with the program; 99% agreed HIV POCT should be routinely offered in pharmacies and 78% were willing to pay for the service. Participants felt the pharmacy was convenient, discreet, and that the pharmacist was supportive and provided education about how to reduce their future risk. Pharmacists felt prepared, confident, and expressed professional satisfaction with offering HIV POCT. Community and public health supports, clear linkage to care plans to refer participants with positive HIV POCT results, and provision of counselling tools were important enabling factors for the program. Pharmacist remuneration, integration with existing healthcare systems, and support for ongoing promotion of HIV POCT availability in pharmacies were identified as needs for future scale-up and sustainability. CONCLUSIONS: A successful model of pharmacy-based POCT, including linkage to care, was developed. Further research is needed to determine the effectiveness and cost-effectiveness of this approach in finding new diagnoses and linking them with care. TRIAL REGISTRATION: Retrospectively registered with clinicaltrials.gov (NCT03210701) on July 6, 2017.

Timeliness of diagnosis of HIV in Newfoundland and Labrador, Canada: A mixed-methods study.

Background: Late diagnosis of HIV is associated with poor outcomes and increased cost. Novel HIV testing promotion strategies may reduce late diagnosis. The purpose of this study was to determine the timeliness of HIV testing in Newfoundland and Labrador (NL), missed opportunities for testing, and barriers to HIV testing. Methods: Demographic and clinical information from individuals diagnosed with HIV in NL from 2006-2016 was retrospectively reviewed. Patients were also invited to participate in semi-structured interviews regarding knowledge about HIV transmission, risk associated with their behaviour, testing decision making, and testing opportunities. Results: Fifty-eight new HIV diagnoses occurred during the study period: 53/58 (91.4%) were male and 33/58 (56.9%) were men who have sex with men. The mean age at diagnosis was 40.6 (SD 11.05) years. CD4 count at diagnosis ranged from 2 to 1,408 cells/mm3, with a mean of 387 cells/mm3. For 39/58 (67.2%) of individuals, the first-ever HIV test was positive. Of the 58 patients, 55 (94.8%) had had health care contact within the 5 years prior to diagnosis (mean 13.7 contacts). Heterosexual men were more likely to present with a late diagnosis (p = 0.049). Ten (17.2%) individuals agreed to an interview. Thematic analysis revealed that barriers to testing were stigma, negative health care interactions, denial, and fear of the diagnosis. Conclusions: HIV diagnosis is made later in NL than in other Canadian provinces. Late diagnosis may be prevented if HIV testing became a routine testing procedure.

Historique: Un diagnostic tardif de VIH s'associe à un mauvais pronostic et à des coûts élevés. De nouvelles stratégies de promotion du test de dépistage du VIH limiteraient les diagnostics tardifs. La présente étude visait à déterminer la rapidité d'exécution du test de VIH à Terre-Neuve-et-Labrador (TNL), les occasions ratées d'effectuer le test et les obstacles à l'effectuer. Méthodologie: Les auteurs ont procédé à une analyse rétrospective de l'information démographique et clinique des personnes ayant reçu un diagnostic de VIH à TNL entre 2006 et 2016. Les patients ont également été invités à participer à des entrevues semi-structurées au sujet de leurs connaissances sur la transmission du VIH, du risque associé à leurs comportements, de la décision de subir le test et des possibilités de le subir. Résultats: Cinquante-huit nouveaux diagnostics de VIH ont été posés pendant la période de l'étude : 53 sur 58 (91,4 %) étaient des hommes et 33 sur 58 (56,9 %), des hommes ayant des relations sexuelles avec d'autres hommes. Les patients avaient un âge moyen de 40,6 ans (± 11,05) au diagnostic. Leur numération de lymphocytes T CD4 au diagnostic se situait entre 2 et 1 408 cellules/mm3, pour une moyenne de 387 cellules/mm3. Pour 39 des 58 patients (67,2 %), le tout premier test de dépistage du VIH avait été positif. Des 58 patients, 55 (94,8 %) avaient eu des contacts avec le milieu de la santé dans les cinq années précédant le diagnostic (moyenne de 13,7 contacts). Les hommes hétérosexuels étaient plus susceptibles d'obtenir un diagnostic tardif (p = 0,049). Dix patients (17,2 %) ont accepté une entrevue. Une analyse thématique a révélé que les préjugés, des interactions négatives avec le milieu de la santé, le déni et la crainte du diagnostic étaient les obstacles aux tests. Conclusions: Le diagnostic de VIH est plus tardif à TNL que dans les autres provinces canadiennes. Il serait possible de prévenir les diagnostics tardifs si le test du VIH devenait systématique.

Responses to pandemic ASO3-adjuvanted A/California/07/09 H1N1 influenza vaccine in human immunodeficiency virus-infected individuals.

BACKGROUND: Influenza infection may be more serious in human immunodeficiency virus (HIV)-infected individuals, therefore, vaccination against seasonal and pandemic strains is highly advised. Seasonal influenza vaccines have had no significant negative effects in well controlled HIV infection, but the impact of adjuvanted pandemic A/California/07/2009 H1N1 influenza hemaglutinin (HA) vaccine, which was used for the first time in the Canadian population as an authorized vaccine in autumn 2009, has not been extensively studied. OBJECTIVE: Assess vaccine-related effects on CD4(+) T cell counts and humoral responses to the vaccine in individuals attending the Newfoundland and Labrador Provincial HIV clinic. METHODS: A single dose of Arepanrix™ split vaccine including 3.75 µg A/California/07/2009 H1N1 HA antigen and ASO3 adjuvant was administered to 81 HIV-infected individuals by intramuscular injection. Plasma samples from shortly before, and 1-5 months after vaccination were collected from 80/81 individuals to assess humoral anti-H1N1 HA responses using a sensitive microbead-based array assay. Data on CD4(+) T cell counts, plasma viral load, antiretroviral therapy and patient age were collected from clinical records of 81 individuals. RESULTS: Overall, 36/80 responded to vaccination either by seroconversion to H1N1 HA or with a clear increase in anti-H1N1 HA antibody levels. Approximately 1/3 (28/80) had pre-existing anti-H1N1 HA antibodies and were more likely to respond to vaccination (22/28). Responders had higher baseline CD4(+) T cell counts and responders without pre-existing antibodies against H1N1 HA were younger than either non-responders or responders with pre-existing antibodies. Compared to changes in their CD4(+) T cell counts observed over a similar time period one year later, vaccine recipients displayed a minor, transient fall in CD4(+) T cell numbers, which was greater amongst responders. CONCLUSIONS: We observed low response rates to the 2009 pandemic influenza vaccine among HIV-infected individuals without pre-existing antibodies against H1N1 HA and a minor transient fall in CD4(+) T cell numbers, which was accentuated in responders. A single injection of the Arepanrix™ pandemic A/California/07/2009 H1N1 HA split vaccine may be insufficient to induce protective immunity in HIV-infected individuals without pre-existing anti-H1N1 HA responses.