Search

Background: HIV drug resistance (HIV-DR) may jeopardize the benefit of antiretroviral therapy (ART) in treatment and prevention. This study utilized viral phylogenetics to resolve the influence of transmission networks on sustaining the spread of HIV-DR in Quebec spanning 2002 to 2022. Methods: Time trends in acquired (ADR) and transmitted drug resistance (TDR) were delineated in treatment-experienced (n = 3500) and ART-naïve persons (n = 6011) with subtype B infections. Similarly, non-B-subtype HIV-DR networks were assessed pre- (n = 1577) and post-ART experience (n = 488). Risks of acquisition of resistance-associated mutations (RAMs) were related to clustering using 1, 2–5, vs. 6+ members per cluster as categorical variables. Results: Despite steady declines in treatment failure and ADR since 2007, rates of TDR among newly infected, ART-naive persons remained at 14% spanning the 2007–2011, 2012–2016, and 2017–2022 periods. Notably, half of new infections among men having sex with men and heterosexual groups were linked in large, clustered networks having a median of 35 (14–73 IQR) and 16 (9–26 IQR) members per cluster, respectively. Cluster membership and size were implicated in forward transmission of non-nucleoside reverse transcriptase inhibitor NNRTI RAMs (9%) and thymidine analogue mutations (TAMs) (5%). In contrast, transmission of M184V, K65R, and integrase inhibitors (1–2%) remained rare. Levels of TDR reflected viral replicative fitness. The median baseline viremia in ART-naïve groups having no RAMs, NNRTI RAMs, TAMs, and M184VI were 46.088, 38,447, 20,330, and 6811 copies/mL, respectively (p < 0.0001). Conclusion: Phylogenetics emphasize the need to prioritize ART and pre-exposure prophylaxis strategies to avert the expansion of transmission cascades of HIV-DR. [ABSTRACT FROM AUTHOR]

Interleukin 32 (IL-32) is a potent multi-isoform proinflammatory cytokine, which is upregulated in people with HIV (PWH) and is associated with cardiovascular disease (CVD) risk. However, the impact of IL-32 isoforms on CD4 T-cell cardiotropism, a mechanism potentially contributing to heart inflammation, remains unknown. Here we show that IL-32 isoforms β and γ induce the generation of CCR4+CXCR3+ double positive (DP) memory CD4 T-cell subpopulation expressing the tyrosine kinase receptor c-Met, a phenotype associated with heart-homing of T cells. Our ex vivo studies on PWH show that the frequency of DP CD4 T cells is significantly higher in individuals with, compared to individuals without, subclinical atherosclerosis and that DP cells from antiretroviral-naive and treated individuals are highly enriched with HIV DNA. Together, these data demonstrate that IL-32 isoforms have the potential to induce heart-homing of HIV-infected CD4 T cells, which may further aggravate heart inflammation and CVD in PWH. [ABSTRACT FROM AUTHOR]

Background: Gay, bisexual, and other men (GBM) who have sex with men living with HIV in serodifferent couples (one partner living with HIV, the other HIV-negative) may encounter unique sexual health challenges. This study aimed to explore their definition of sexual health that could improve service provision. Methods: We interviewed 10 gay-identified men living with HIV from 2017 to 2019 as part of CTNPT013, a study on the sexual health of HIV serodifferent GBM couples conducted at two HIV-specialised clinics in Montreal, Canada. Participants partook in semi-structured interviews on the meaning of sexual health. We performed a content analysis of interview transcripts, coding them according to the 10 dimensions of Robinson's Sexual Health Model. Results: Mean age of interviewees was 35.4 years (s.d.,10.2; range, 20–53). Every dimension of Robinson's model was spontaneously evoked, except for body image and spirituality. All men indicated intimacy/relationships (e.g. sexual agreements) and sexual health care/safer sex (e.g. HIV management, risk behaviours) as relevant aspects of sexual health. Other dimensions included: positive sexuality (n = 7), such as pleasure and enjoyment during sex; talking about sex (n = 5), which mainly concerned HIV disclosure; sexual functioning (n = 4); challenges to sexual health (n = 3), including substance abuse; and culture/sexual identity (n = 3). Two participants (n = 2) cited masturbation/fantasy. Conclusions: This study emphasises the multi-faceted nature of sexual health for gay men with HIV in serodifferent couples and the pivotal roles of relationships, HIV, risk management (e.g. via health care, knowledge), and positive sexual experiences. These dimensions could be considered in sexual health promotion interventions targeting this population. Sexual health is a complex, multi-dimensional concept; however, much research on the topic is focused on sexually transmitted infections and risk reduction. Given their status as a key population for sexual health promotion, we interviewed 10 gay men living with HIV about the meaning of sexual health. While all mentioned sexual health care and safer sex (e.g. HIV management), most also addressed intimacy and relationships and well as positive sexuality as key components of sexual health. [ABSTRACT FROM AUTHOR]

Interleukin 32 (IL-32) is a potent multi-isoform proinflammatory cytokine, which is upregulated in people with HIV (PWH) and is associated with cardiovascular disease (CVD) risk. However, the impact of IL-32 isoforms on CD4 T-cell cardiotropism, a mechanism potentially contributing to heart inflammation, remains unknown. Here we show that IL-32 isoforms β and γ induce the generation of CCR4+CXCR3+ double positive (DP) memory CD4 T-cell subpopulation expressing the tyrosine kinase receptor c-Met, a phenotype associated with heart-homing of T cells. Our ex vivo studies on PWH show that the frequency of DP CD4 T cells is significantly higher in individuals with, compared to individuals without, subclinical atherosclerosis and that DP cells from antiretroviral-naive and treated individuals are highly enriched with HIV DNA. Together, these data demonstrate that IL-32 isoforms have the potential to induce heart-homing of HIV-infected CD4 T cells, which may further aggravate heart inflammation and CVD in PWH., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)