ABSTRACT
Social determinants are increasingly understood as key contributors to patterns of heightened risk for HIV acquisition and suboptimal care and treatment outcomes. Yet, the ability to rigorously model, map and measure these nuanced social dynamics has been a challenge, resulting in limited examples of effective interventions and resource allocation. In 2016, the United States National Institute of Mental Health (NIMH) and the National Institute of Allergy and Infectious Diseases (NIAID) issued a Request for Applications calling for methodological innovations around the social determinants of HIV. In May of 2019, NIMH, in collaboration with American University's Center on Health, Risk and Society and the DC Center for AIDS Research, sponsored a symposium to bring together the funded teams to share accomplishments, distill lessons learned and reflect on the state of the science with other key stakeholders. Presentations focused on causal inference, multi-level analysis and mathematical modeling (Models); geospatial analytics and ecological momentary assessments (Maps); and measurement of social and structural determinants including inequalities and stigmas (Measures). Cross-cutting and higher-level themes were discussed and largely focused on the importance of critical and careful integration of social theory, community engagement and mixed methodologies into research on the social determinants of HIV.
Subject(s)
HIV Infections , Social Determinants of Health , HIV Infections/epidemiology , HIV Infections/prevention & control , Humans , Social Stigma , United StatesABSTRACT
Older age is a strong predictor of accelerated human immunodeficiency virus (HIV) disease progression. We investigated the possible immunologic basis of this interaction by comparing older (>/=45 years) and younger (=30 years) HIV-infected adults with simultaneously enrolled, aged-matched, healthy volunteers. Cross-sectional comparisons suggested age-associated reductions in naive CD8(+) cells and in the expression of CD28(+) on CD8(+) cells among both HIV-infected subjects and control subjects. Opposite patterns of CD4(+) and CD8(+) cell differences were apparent between these subject groups. HIV infection, but not age, was associated with impairments in delayed-type hypersensitivity responses, lymphoproliferation, and spontaneous apoptosis and with alterations in expression of chemokine receptors CCR5 and CXCR4. Reduced thymic volumes were associated with age and with HIV infection among younger, but not older, subjects. Because of their common association with age and HIV disease, naive CD8(+) cell depletion, diminished CD28 expression on CD8(+) cells, and reduced thymic volumes are possible correlates of the interaction of age with HIV disease.
Subject(s)
Aging/immunology , CD28 Antigens/metabolism , CD8-Positive T-Lymphocytes/immunology , HIV Infections/immunology , Thymus Gland/pathology , Adolescent , Adult , Aged , CD8-Positive T-Lymphocytes/cytology , CD8-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/pathology , Cross-Sectional Studies , Disease Progression , Female , Gene Expression Regulation , HIV Infections/pathology , HIV-1 , Humans , Male , Middle Aged , Phenotype , Thymus Gland/cytology , Thymus Gland/immunologyABSTRACT
To ascertain whether CD4(+) lymphocyte increases induced by interleukin (IL)-2 enhanced in vivo immune responses, 38 human immunodeficiency virus (HIV)-infected patients who had received highly active antiretroviral therapy (HAART) or HAART and IL-2 for at least 60 weeks were immunized with tetanus toxoid, inactivated glycoprotein 120-depleted HIV-1, and hepatitis A and B vaccines. Despite dramatic increases in CD4(+) lymphocyte counts, IL-2 did not enhance immunization responses.
Subject(s)
CD4-Positive T-Lymphocytes/cytology , CD4-Positive T-Lymphocytes/drug effects , HIV Infections/immunology , Interleukin-2/pharmacology , Lymphocyte Activation/drug effects , AIDS Vaccines/immunology , Adjuvants, Immunologic/pharmacology , Adult , Anti-HIV Agents/therapeutic use , Antiretroviral Therapy, Highly Active , CD4 Lymphocyte Count , CD4-Positive T-Lymphocytes/immunology , Drug Therapy, Combination , HIV Infections/drug therapy , Hepatitis A Vaccines/immunology , Hepatitis B Vaccines/immunology , Humans , Male , Tetanus Toxoid/immunologyABSTRACT
The effect of etanercept, a soluble p75 tumor necrosis factor (TNF) receptor:Fc fusion protein (Enbrel; Immunex, Seattle, WA) on plasma cytokines was evaluated in 11 HIV-infected subjects receiving highly active antiretroviral therapy (HAART) for 28 weeks with or without subcutaneous or intravenous recombinant human interleukin 2 (rhIL-2). Plasma IL-6 and C-reactive protein (CRP) levels increased after rhIL-2 treatment. Etanercept pretreatment attenuated these increases. Median plasma IL-6 levels were 20.29 pg/ml 4 days after rhIL-2 and 7.87 pg/ml 4 days after etanercept and rhIL-2 (p = 0.22); median CRP levels were 78.73 and 46.16 microg/ml, respectively (p = 0.03). An effect on TNF bioactivity could not be assessed as all measurements were below limits of detection. No significant changes were seen in temperature or plasma levels of IL-4, IL-10, IL-12, interferon gamma, or HIV-1 RNA levels. All subjects had undetectable or low-level HIV-1 RNA levels before etanercept dosing. One subject died; however, her death was thought to be unrelated to etanercept. Pretreatment with etanercept may blunt activation of IL-6 and CRP expression induced by rhIL-2. The safety and utility of etanercept in HIV-infected persons should be explored further.