Clinical-epidemiological features of HIV-infected patients diagnosed at age of 50 years or older

HIV/AIDS prevention and care efforts are directed to individuals of reproductive age (15–49 yrs). With the extension of sexual life of older people, they became a growing population at risk of HIV infection, usually not included in prevention strategies. In order to evaluate clinical profile of HIV/AIDS pts diagnosed at 50 yrs or older assisted in an HIV outpatient center in Buenos Aires, we retrospectively assessed clinical records of pts initiating care between Jan 1986 and Dec 2011. Age, CD4 cells and viral load (pVL) at HIV diagnosis and most recent value, opportunistic infections (OIs), co-morbidities and antiretroviral therapy (ARV) were recorded. Of 10,998 pts assisted in the 26-yr period, 495 (4.5%) were≥50 yrs old at HIV diagnosis; median annual diagnoses: 18.5 (IQR 3.3–30.3) without significant changes in the last 20 yrs. Demographics: median age 54.7 yrs (IQR 51.8–59.2, rank 50–80), 76.6% male. Risk behavior: HTX 61.4%, MSM 34.1%, others 4.4%. 55.4% of HIV diagnoses occurred during hospitalization or simultaneously with acute OIs. One third (n=176) had AIDS at diagnosis, 24% had history of STDs. HCV co-infection 5.7%, past HBV infection 28.1% and chronic HBV infection 5.1%. Median CD4 cells at HIV diagnosis: 223.5 (13.7%) (IQR 98.8–420.3), initial pVL 60,000 cp/mL (IQR 9,995.5–208,391). 69.3% of pts started ARV therapy during follow-up (FU), and the median time between diagnosis and treatment initiation was 3.4 mo (IQR 0.7–14); 56.9% of them started a non-nucleoside-based regimen (ZDV/3TC/EFV), 28.3% a PI-based regimen (ZDV/3TC/IDV) and 14.6% a nucleoside-based regimen (ZDV/ddI pre-HAART era). After a year (±6 mo), 63.8% pts achieved undetectable pVL and gained 136 CD4 cells from BSL (IQR 83–204). After 40.6 mo of FU (IQR 6.7-89.8), 66.3% are alive, 7.1% died (68.6% of HIV-related diseases) and 26.7% are lost to FU. Co-morbidities were present in 125 (25.3%), mainly hypertension, increased lipids, CVD and DBT. Among treated pts, 70.6% achieved pVL<50 cp/mL, with a median increase of CD4 cells up to 410 (22%) (IQR 281.5–563.9) from BSL. 51% (176) changed ARV therapy due to toxicity/AE: 54.5%, ARV failure: 29.5% and simplification: 14.8%. Stable HIV epidemic in older people reinforce the need of specific prevention approaches, while growing age of HIV individuals in care highlights to consider risks associated to older age. Late presentation to care needs to be specifically addressed. Response to treatment is remarkable high in this population

Early skewed differentiation and PD-1 expression in CD4+ cells relate to immune dysfunction and viral persistence in individuals living with HIV 1 year post-cART initiation

Achieving HIV functional cure is a priority. Strategies such as adoptive cell transfer have been assayed, without success yet mainly due to immune dysfunctions observed among individuals. Samples from 25 HIV+ subjects were collected at diagnosis (baseline sample, BSL) and one year post-cART initiation (post- cART ). At BSL, bulk and HIV-specific CD4 phenotype (CD45RO , CCR 7, CD95 and PD1 expression) was assessed by flow cytometry after a short stimulation with HIV peptides. Also, proportion of CD4+/HLA-DR+/ CD38+ cells was measured. At post-cART , HIV-specific CD8TC s were obtained after 2-week expansion with peptides. Phenotype and antiviral activity (VIA and VITA L assays) were evaluated post-expansion. Plasma CXCL10 (IP-10) was assessed by ELISA. Cell-associated HIV DNA (total and integrated) and unspliced (US) and multiply-spliced (MS) RNA were quantified by real-time PCR. Non-parametric statistics were applied. Early CD4TC exhaustion, elevated activation and inadequate differentiation seem to be associated with viral persistence, inflammation, as well as with the phenotype and antiviral capacity of HIV-specific CD8TC s that persist one year after cART is initiated. These parameters could serve as predictors of CD8TC function on treated subjects.Fil: Salido, Jimena Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Czernikier, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Trifone, César Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Figueroa, M. I.. Fundación Huésped; ArgentinaFil: Salomon, Horacio Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Cahn, P.. Fundación Huésped; ArgentinaFil: Sued, O.. Fundación Huésped; ArgentinaFil: Laufer, Natalia Lorna. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Ghiglione, Yanina Alexandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Turk, Gabriela Julia Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentin

A global call for action to include gender in research impact assessment

Global investment in biomedical research has grown significantly over the last decades, reaching approximately a quarter of a trillion US dollars in 2010. However, not all of this investment is distributed evenly by gender. It follows, arguably, that scarce research resources may not be optimally invested (by either not supporting the best science or by failing to investigate topics that benefit women and men equitably). Women across the world tend to be significantly underrepresented in research both as researchers and research participants, receive less research funding, and appear less frequently than men as authors on research publications. There is also some evidence that women are relatively disadvantaged as the beneficiaries of research, in terms of its health, societal, and economic impacts. Historical gender biases may have created a path dependency that means that the research system and the impacts of research are biased towards male researchers and male beneficiaries, making it inherently difficult (though not impossible) to eliminate gender bias. In this commentary, we – a group of scholars and practitioners from Africa, America, Asia, and Europe– argue that gender-sensitive research impact assessment could become a force for good in moving science policy and practice towards gender equity. Research impact assessment is the multidisciplinary field of scientific inquiry that examines the research process to maximise scientific, societal, and economic returns on investment in research. It encompasses many theoretical and methodological approaches that can be used to investigate gender bias and recommend actions for change to maximise research impact. We offer a set of recommendations to research funders, research institutions, and research evaluators who conduct impact assessment on how to include and strengthen analysis of gender equity in research impact assessment and issue a global call for action

Dynamics of Adrenal Steroids Are Related to Variations in Th1 and Treg Populations during Mycobacterium tuberculosis Infection in HIV Positive Persons

Tuberculosis (TB) remains the most frequent cause of illness and death from an infectious agent, and its interaction with HIV has devastating effects. We determined plasma levels of dehydroepiandrosterone (DHEA), its circulating form DHEA-suphate (DHEA-s) and cortisol in different stages of M. tuberculosis infection, and explored their role on the Th1 and Treg populations during different scenarios of HIV-TB coinfection, including the immune reconstitution inflammatory syndrome (IRIS), a condition related to antiretroviral treatment. DHEA levels were diminished in HIV-TB and HIV-TB IRIS patients compared to healthy donors (HD), HIV+ individuals and HIV+ individuals with latent TB (HIV-LTB), whereas dehydroepiandrosterone sulfate (DHEA-s) levels were markedly diminished in HIV-TB IRIS individuals. HIV-TB and IRIS patients presented a cortisol/DHEA ratio significantly higher than HIV+, HIV-LTB and HD individuals. A positive correlation was observed between DHEA-s and CD4 count among HIV-TB individuals. Conversely, cortisol plasma level inversely correlated with CD4 count within HIV-TB individuals. M. tuberculosis-specific Th1 lymphocyte count was increased after culturing PBMC from HIV-TB individuals in presence of DHEA. We observed an inverse correlation between DHEA-s plasma level and Treg frequency in co-infected individuals, and CD4+FoxP3+ Treg frequency was increased in HIV-TB and IRIS patients compared to other groups. Strikingly, we observed a prominent CD4+CD25-FoxP3+ population across HIV-TB and HIV-TB IRIS patients, which frequency correlated with DHEA plasma level. Finally, DHEA treatment negatively regulated FoxP3 expression without altering Treg frequency in co-infected patients. These data suggest an enhancing role for DHEA in the immune response against M. tuberculosis during HIV-TB coinfection and IRIS

Metabolic Rift or Metabolic Shift? Dialectics, Nature, and the World-Historical Method

Abstract In the flowering of Red-Green Thought over the past two decades, metabolic rift thinking is surely one of its most colorful varieties. The metabolic rift has captured the imagination of critical environmental scholars, becoming a shorthand for capitalism’s troubled relations in the web of life. This article pursues an entwined critique and reconstruction: of metabolic rift thinking and the possibilities for a post-Cartesian perspective on historical change, the world-ecology conversation. Far from dismissing metabolic rift thinking, my intention is to affirm its dialectical core. At stake is not merely the mode of explanation within environmental sociology. The impasse of metabolic rift thinking is suggestive of wider problems across the environmental social sciences, now confronted by a double challenge. One of course is the widespread—and reasonable—sense of urgency to evolve modes of thought appropriate to an era of deepening biospheric instability. The second is the widely recognized—but inadequately internalized—understanding that humans are part of nature

Cabotegravir for HIV Prevention in Cisgender Men and Transgender Women

Background: Safe and effective long-acting injectable agents for preexposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection are needed to increase the options for preventing HIV infection. Methods: We conducted a randomized, double-blind, double-dummy, noninferiority trial to compare long-acting injectable cabotegravir (CAB-LA, an integrase strand-transfer inhibitor [INSTI]) at a dose of 600 mg, given intramuscularly every 8 weeks, with daily oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) for the prevention of HIV infection in at-risk cisgender men who have sex with men (MSM) and in at-risk transgender women who have sex with men. Participants were randomly assigned (1:1) to receive one of the two regimens and were followed for 153 weeks. HIV testing and safety evaluations were performed. The primary end point was incident HIV infection. Results: The intention-to-treat population included 4566 participants who underwent randomization; 570 (12.5%) identified as transgender women, and the median age was 26 years (interquartile range, 22 to 32). The trial was stopped early for efficacy on review of the results of the first preplanned interim end-point analysis. Among 1698 participants from the United States, 845 (49.8%) identified as Black. Incident HIV infection occurred in 52 participants: 13 in the cabotegravir group (incidence, 0.41 per 100 person-years) and 39 in the TDF-FTC group (incidence, 1.22 per 100 person-years) (hazard ratio, 0.34; 95% confidence interval, 0.18 to 0.62). The effect was consistent across prespecified subgroups. Injection-site reactions were reported in 81.4% of the participants in the cabotegravir group and in 31.3% of those in the TDF-FTC group. In the participants in whom HIV infection was diagnosed after exposure to CAB-LA, INSTI resistance and delays in the detection of HIV infection were noted. No safety concerns were identified. Conclusions: CAB-LA was superior to daily oral TDF-FTC in preventing HIV infection among MSM and transgender women. Strategies are needed to prevent INSTI resistance in cases of CAB-LA PrEP failure

Sex in the shadow of HIV:A systematic review of prevalence, risk factors, and interventions to reduce sexual risk-taking among HIVpositive adolescents and youth in sub-Saharan Africa

Background Evidence on sexual risk-taking among HIV-positive adolescents and youth in sub-Saharan Africa is urgently needed. This systematic review synthesizes the extant research on prevalence, factors associated with, and interventions to reduce sexual risk-taking among HIV-positive adolescents and youth in sub-Saharan Africa. Methods Studies were located through electronic databases, grey literature, reference harvesting, and contact with researchers. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Quantitative studies that reported on HIV-positive participants (10-24 year olds), included data on at least one of eight outcomes (early sexual debut, inconsistent condom use, older partner, transactional sex, multiple sexual partners, sex while intoxicated, sexually transmitted infections, and pregnancy), and were conducted in sub-Saharan Africa were included. Two authors piloted all processes, screened studies, extracted data independently, and resolved any discrepancies. Due to variance in reported rates and factors associated with sexual risk-taking, meta-analyses were not conducted. Results 610 potentially relevant titles/abstracts resulted in the full text review of 251 records. Forty-two records (n=35 studies) reported one or multiple sexual practices for 13,536 HIV-positive adolescents/youth from 13 sub-Saharan African countries. Seventeen cross-sectional studies reported on individual, relationship, family, structural, and HIV-related factors associated with sexual risk-taking. However, the majority of the findings were inconsistent across studies, and most studies scored Conclusions Sexual risk-taking among HIV-positive adolescents and youth is high, with inconclusive evidence on potential determinants. Few known studies test secondary HIV-prevention interventions for HIV-positive youth. Effective and feasible low-cost interventions to reduce risk are urgently needed for this group.</p