Social Categorisation and Social Identification: The Mediating Role of Social Isolation and Loneliness in Adolescents Living with HIV

BACKGROUND: Social isolation and loneliness are associated with living with a chronic condition particularly where stigma is a factor. Our study aimed to examine the lived experience of adolescents living with HIV in relation to isolation because of their diagnosis and consequences of disclosure. Giddens' structuration theory was used as an analytic framework to identify the potential mechanisms underlying adolescents living with HIV's experiences. METHOD: Longitudinal in-depth interviews were conducted with 20 adolescents living with HIV aged 15-24 years with each participant taking part in three interviews (total 60) between September 2020 and October 2021. Thematic analysis was performed using Braun and Clarke's steps for coding and analysing qualitative data and informed by the structuration theory framework. RESULTS: The findings indicated that adolescents living with HIV have agency and make conscious choices about sharing their status. However, these choices are influenced by their experiences in their community. The discrimination and negative judgements they often experience prevent them from disclosing their status. Stigma, discrimination, and psychological distress contribute to the isolation that adolescents and young adults living with HIV experience. The limited disclosure itself can lead to them becoming isolated and lonely. CONCLUSION: The negative experiences which adolescents living with HIV face can have an impact not only on their psychological wellbeing but also on their decision to disclose and seek support. These experiences may lead to social isolation and loneliness, an unintended consequence of their action in protecting themselves from the conditions created by the structures/environment in which they live

Social Categorisation and Social Identification: The Mediating Role of Social Isolation and Loneliness in Adolescents Living with HIV

BACKGROUND: Social isolation and loneliness are associated with living with a chronic condition particularly where stigma is a factor. Our study aimed to examine the lived experience of adolescents living with HIV in relation to isolation because of their diagnosis and consequences of disclosure. Giddens' structuration theory was used as an analytic framework to identify the potential mechanisms underlying adolescents living with HIV's experiences. METHOD: Longitudinal in-depth interviews were conducted with 20 adolescents living with HIV aged 15-24 years with each participant taking part in three interviews (total 60) between September 2020 and October 2021. Thematic analysis was performed using Braun and Clarke's steps for coding and analysing qualitative data and informed by the structuration theory framework. RESULTS: The findings indicated that adolescents living with HIV have agency and make conscious choices about sharing their status. However, these choices are influenced by their experiences in their community. The discrimination and negative judgements they often experience prevent them from disclosing their status. Stigma, discrimination, and psychological distress contribute to the isolation that adolescents and young adults living with HIV experience. The limited disclosure itself can lead to them becoming isolated and lonely. CONCLUSION: The negative experiences which adolescents living with HIV face can have an impact not only on their psychological wellbeing but also on their decision to disclose and seek support. These experiences may lead to social isolation and loneliness, an unintended consequence of their action in protecting themselves from the conditions created by the structures/environment in which they live

Magnitude and Kinetics of CD8+ T Cell Activation during Hyperacute HIV Infection Impact Viral Set Point

CD8[superscript +] T cells contribute to the control of HIV, but it is not clear whether initial immune responses modulate the viral set point. We screened high-risk uninfected women twice a week for plasma HIV RNA and identified 12 hyperacute infections. Onset of viremia elicited a massive HIV-specific CD8[superscript +] T cell response, with limited bystander activation of non-HIV memory CD8[superscript +] T cells. HIV-specific CD8[superscript +] T cells secreted little interferon-γ, underwent rapid apoptosis, and failed to upregulate the interleukin-7 receptor, known to be important for T cell survival. The rapidity to peak CD8[superscript +] T cell activation and the absolute magnitude of activation induced by the exponential rise in viremia were inversely correlated with set point viremia. These data indicate that rapid, high magnitude HIV-induced CD8[superscript +] T cell responses are crucial for subsequent immune control of acute infection, which has important implications for HIV vaccine design.Bill & Melinda Gates FoundationCollaboration for AIDS Vaccine DiscoveryWitten Family FoundationDan and Marjorie SullivanUrsula BrunnerGary and Loren CohenMark and Lisa Schwartz Foundation,International AIDS Vaccine Initiative (UKZNRSA1001)National Institute of Allergy and Infectious Diseases (U.S.) (R37AI067073)Center for AIDS Research (P30 AI060354

Unsuppressed HIV infection impairs T cell responses to SARS-CoV-2 infection and abrogates T cell cross-recognition

In some instances, unsuppressed HIV has been associated with severe COVID-19 disease, but the mechanisms underpinning this susceptibility are still unclear. Here, we assessed the impact of HIV infection on the quality and epitope specificity of SARS-CoV-2 T cell responses in the first wave and second wave of the COVID-19 epidemic in South Africa. Flow cytometry was used to measure T cell responses following peripheral blood mononuclear cell stimulation with SARS-CoV-2 peptide pools. Culture expansion was used to determine T cell immunodominance hierarchies and to assess potential SARS-CoV-2 escape from T cell recognition. HIV-seronegative individuals had significantly greater CD4+ T cell responses against the Spike protein compared to the viremic people living with HIV (PLWH). Absolute CD4 count correlated positively with SARS-CoV-2-specific CD4+ and CD8+ T cell responses (CD4 r=0.5, p=0.03; CD8 r=0.5, p=0.001), whereas T cell activation was negatively correlated with CD4+ T cell responses (CD4 r=−0.7, p=0.04). There was diminished T cell cross-recognition between the two waves, which was more pronounced in individuals with unsuppressed HIV infection. Importantly, we identify four mutations in the Beta variant that resulted in abrogation of T cell recognition. Taken together, we show that unsuppressed HIV infection markedly impairs T cell responses to SARS-Cov-2 infection and diminishes T cell cross-recognition. These findings may partly explain the increased susceptibility of PLWH to severe COVID-19 and also highlights their vulnerability to emerging SARS-CoV-2 variants of concern

Low pre-existing endemic human coronavirus (HCoV-NL63)-specific T cell frequencies are associated with impaired SARS-CoV-2-specific T cell responses in people living with HIV

Background: Understanding how HIV affects SARS-CoV-2 immunity is crucial for managing COVID-19 in sub-Saharan populations due to frequent coinfections. Our previous research showed that unsuppressed HIV is associated with weaker immune responses to SARS-CoV-2, but the underlying mechanisms are unclear. We investigated how pre-existing T cell immunity against an endemic human coronavirus HCoV-NL63 impacts SARS-CoV-2 T cell responses in people living with HIV (PLWH) compared to uninfected individuals, and how HIV-related T cell dysfunction influences responses to SARS-CoV-2 variants. Methods: We used flow cytometry to measure T cell responses following PBMC stimulation with peptide pools representing beta, delta, wild-type, and HCoV-NL63 spike proteins. Luminex bead assay was used to measure circulating plasma chemokine and cytokine levels. ELISA and MSD V-PLEX COVID-19 Serology and ACE2 Neutralization assays were used to measure humoral responses. Results: Regardless of HIV status, we found a strong positive correlation between responses to HCoV-NL63 and SARS-CoV-2. However, PLWH exhibited weaker CD4+ T cell responses to both HCoV-NL63 and SARS-CoV-2 than HIV-uninfected individuals. PLWH also had higher proportions of functionally exhausted (PD-1high) CD4+ T cells producing fewer proinflammatory cytokines (IFNγ and TNFα) and had elevated plasma IL-2 and IL-12(p70) levels compared to HIV-uninfected individuals. HIV status didn’t significantly affect IgG antibody levels against SARS-CoV-2 antigens or ACE2 binding inhibition activity. Conclusion: Our results indicate that the decrease in SARS-CoV-2 specific T cell responses in PLWH may be attributable to reduced frequencies of pre-existing cross-reactive responses. However, HIV infection minimally affected the quality and magnitude of humoral responses, and this could explain why the risk of severe COVID-19 in PLWH is highly heterogeneous

If not now, when? Time for the European Union to define a global health strategy

Speakman, E. M., McKee, M., & Coker, R. (2017). If not now, when? Time for the European Union to define a global health strategy. Lancet Global Health, 5(4), e392-e393. https://doi.org/10.1016/S2214-109X%2817%2930085-

Asymptomatic Bacterial Vaginosis in Pregnancy and Missed Opportunities for Treatment: A Cross-Sectional Observational Study

Background. High rates of bacterial vaginosis (BV) have been described in nonpregnant South African women. Studies of BV in South African pregnant women are sparse. Diagnosis and prompt treatment of BV in pregnancy are expected to have a positive impact on pregnancy outcomes and HIV prevention. This study was undertaken to determine the prevalence of BV in pregnant women in a high HIV burden periurban setting in KwaZulu-Natal and explore how to enhance BV diagnosis in this setting where syndromic management of sexually transmitted diseases is the standard of care. Methods. In this cross-sectional study, consenting HIV uninfected pregnant women were examined for abnormal vaginal discharge; nurses determined the vaginal pH and collected a vaginal swab for Gram-stain and Nugent scoring. Findings. Among 750 HIV uninfected pregnant women, 280 (37.3%; 95%CI 33.9-40.9) tested positive for BV. Using a vaginal pH > 4.4, 65% of women with BV were correctly identified, while an abnormal vaginal discharge correctly identified a significantly lower proportion (52.9%) of women with BV (p=0.005). The sensitivity, specificity, and positive and negative predictive values of vaginal pH testing were 65.9% (95%CI 60.0 – 71.5%), 61.4% (95%CI 56.8 – 65.9%), and 50.1% and 75.4%, respectively. The 20-24 year-old pregnant women were twice more likely to test positive for BV than the adolescent pregnant women (43.6% vs 21.1%) (p = 0.037) and BV was not associated with the duration of a sexual relationship, frequency of unprotected sex during pregnancy, number of lifetime sex partners, or the partner’s age. Conclusion. There is a high burden of primarily asymptomatic BV in HIV uninfected pregnant women in this periurban setting. Both the sensitivity and specificity of vaginal pH testing are superior to the symptomatic diagnosis of BV but not good enough to be used as a screening tool

Dual HLA B*42 and B*81-reactive T cell receptors recognize more diverse HIV-1 Gag escape variants

Closely related HLA alleles presenting similar HIV-1 epitopes can be associated with variable clinical outcome. Here the authors report their findings on CD8+ T cell responses to the HIV-1 Gag-p24 TL9 immunodominant epitope in the context of closely related protective and less protective HLA alleles, and their differential effect on viral contro

Differential localization and limited cytotoxic potential of duodenal CD8+Tcells

The duodenum is a major site of HIV persistence during suppressive antiretroviral therapy despite harboring abundant tissue-resident memory (Trm) CD8(+) T cells. The role of duodenal Trm CD8(+) T cells in viral control is still not well defined. We examined the spatial localization, phenotype, and function of CD8(+) T cells in the human duodenal tissue from people living with HIV (PLHIV) and healthy controls. We found that Trm (CD69(+)CD103(hi)) cells were the predominant CD8(+) T cell population in the duodenum. Immunofluorescence imaging of the duodenal tissue revealed that CD103(+)CD8(+) T cells were localized in the intraepithelial region, while CD103(–)CD8(+) T cells and CD4(+) T cells were mostly localized in the lamina propria (LP). Furthermore, HIV-specific CD8(+) T cells were enriched in the CD69(+)CD103(–/lo) population. However, the duodenal HIV-specific CD8(+) Trm cells rarely expressed canonical molecules for potent cytolytic function (perforin and granzyme B) but were more polyfunctional than those from peripheral blood. Taken together, our results show that duodenal CD8(+) Trm cells possess limited perforin-mediated cytolytic potential and are spatially separated from HIV-susceptible LP CD4(+) T cells. This could contribute to HIV persistence in the duodenum and provides critical information for the design of cure therapies

Augmentation of HIV-specific T cell function by immediate treatment of hyperacute HIV-1 infection

Sustained viremia after acute HIV infection is associated with profound CD4⁺ T cell loss and exhaustion of HIV-specific CD8⁺ T cell responses. To determine the impact of combination antiretroviral therapy (cART) on these processes, we examined the evolution of immune responses in acutely infected individuals initiating treatment before peak viremia. Immediate treatment of Fiebig stages I and II infection led to a rapid decline in viral load and diminished magnitude of HIV-specific (tetramer⁺) CD8⁺ T cell responses compared to untreated donors. There was a strong positive correlation between cumulative viral antigen exposure before full cART-induced suppression and immune responses measured by MHC class I tetramers, IFN-γ ELISPOT, and CD8⁺ T cell activation. HIV-specific CD8⁺ T responses of early treated individuals were characterized by increased CD127 and BCL-2 expression, greater in vitro IFN-γ secretion, and enhanced differentiation into effector memory (Tₑₘ) cells. Transcriptional analysis of tetramer⁺ CD8⁺ T cells from treated persons revealed reduced expression of genes associated with activation and apoptosis, with concurrent up-regulation of prosurvival genes including BCL-2, AXL, and SRC. Early treatment also resulted in robust HIV-specific CD4⁺ T cell responses compared to untreated HIV-infected individuals. Our data show that limiting acute viremia results in enhanced functionality of HIV-specific CD4⁺ and CD8⁺ T cells, preserving key antiviral properties of these cells.National Institute of Health (U.S.) (5U24AI118672)National Institute of Health (U.S.) (1U54CA217377)National Institute of Health (U.S.) (1R33CA202820)National Institute of Health (U.S.) (2U19AI089992)National Institute of Health (U.S.) (1R01HL134539)National Institute of Health (U.S.) (2RM1HG006193)National Institute of Health (U.S.) (2R01HL095791)National Institute of Health (U.S.) (P01AI039671)Bill and Melinda Gates Foundation (OPP1139972