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CD4 T follicular helper cells (Tfh) are essential for establishing serological memory and have distinct helper attributes that impact both the quantity and quality of the antibody response. Insights into Tfh subsets that promote antibody persistence and functional capacity can critically inform vaccine design. Based on the Tfh profiles evoked by the live attenuated measles virus vaccine, renowned for its ability to establish durable humoral immunity, we investigated the potential of a Tfh1/17 recall response during the boost phase to enhance persistence of HIV-1 Envelope (Env) antibodies in rhesus macaques. Using a DNA-prime encoding gp160 antigen and Tfh polarizing cytokines (interferon protein-10 (IP-10) and interleukin-6 (IL-6)), followed by a gp140 protein boost formulated in a cationic liposome-based adjuvant (CAF01), we successfully generated germinal center (GC) Tfh1/17 cells. In contrast, a similar DNA-prime (including IP-10) followed by gp140 formulated with monophosphoryl lipid A (MPLA) +QS-21 adjuvant predominantly induced GC Tfh1 cells. While the generation of GC Tfh1/17 cells with CAF01 and GC Tfh1 cells with MPLA +QS-21 induced comparable peak Env antibodies, the latter group demonstrated significantly greater antibody concentrations at week 8 after final immunization which persisted up to 30 weeks (gp140 IgG ng/ml- MPLA; 5500; CAF01, 2155; p

: Introduction: Four counties within the Atlanta, Georgia 20‐county eligible metropolitan area (EMA) are currently prioritized by the US “Ending the HIV Epidemic” (EHE) initiative which aims for a 90% reduction in HIV incidence by 2030. Disparities driving Atlanta's HIV epidemic warrant an examination of local service availability, unmet needs and organizational capacity to reach EHE targets. We conducted a mixed‐methods evaluation of the Atlanta EMA to examine geographic HIV epidemiology and distribution of services, service needs and organization infrastructure for each pillar of the EHE initiative. Methods: We collected 2021 county‐level data (during June 2022), from multiple sources including: AIDSVu (HIV prevalence and new diagnoses), the Centers for Disease Control and Prevention web‐based tools (HIV testing and pre‐exposure prophylaxis [PrEP] locations) and the Georgia Department of Public Health (HIV testing, PrEP screenings, viral suppression and partner service interviews). We additionally distributed an online survey to key local stakeholders working at major HIV care agencies across the EMA to assess the availability of services, unmet needs and organization infrastructure (June−December 2022). The Organizational Readiness for Implementing Change questionnaire assessed the organization climate for services in need of scale‐up or implementation. Results: We found racial/ethnic and geographic disparities in HIV disease burden and service availability across the EMA—particularly for HIV testing and PrEP in the EMA's southern counties. Five counties not currently prioritized by EHE (Clayton, Douglas, Henry, Newton and Rockdale) accounted for 16% of the EMA's new diagnoses, but Conclusions: Service delivery across all EHE pillars must substantially expand to reach national goals and address HIV disparities in metro Atlanta. High‐resolution geographic data on HIV epidemiology and service delivery with community input can provide targeted guidance to support local EHE efforts., INTRODUCTION The Atlanta, Georgia, Metropolitan Statistical Area (MSA) is the eighth largest in the United States and one of the country's fastest‐growing metropolitan areas [1, 2]. The Ryan White HIV/AIDS [...]

CD4 T follicular helper (Tfh) cells are important for the generation of durable and specific humoral protection against viral infections. The degree to which SARS-CoV-2 infection generates Tfh cells and stimulates the germinal center (GC) response is an important question as we investigate vaccine induced immunity against COVID-19. Here, we report that SARS-CoV-2 infection in rhesus macaques, either infused with convalescent plasma, normal plasma, or receiving no infusion, resulted in transient accumulation of pro-inflammatory monocytes and proliferating Tfh cells with a Th1 profile in peripheral blood. CD4 helper cell responses skewed predominantly toward a Th1 response in blood, lung, and lymph nodes. SARS-CoV-2 Infection induced GC Tfh cells specific for the SARS-CoV-2 spike and nucleocapsid proteins, and a corresponding early appearance of antiviral serum IgG antibodies. Collectively, the data show induction of GC responses in a rhesus model of mild COVID-19.

Background: A goal of mucosal human immunodeficiency virus type 1 (HIV-1) vaccines is to generate mucosal plasma cells producing polymeric IgA (pIgA)-neutralizing antibodies at sites of viral entry. However, vaccine immunogens capable of eliciting IgA neutralizing antibodies (nAbs) that recognize tier 2 viral isolates have not yet been identified. Methods: To determine if stabilized native-like HIV-1 envelope (Env) trimers could generate IgA nAbs, we purified total IgA and IgG from the banked sera of six rhesus macaques that had been found in a previous study to develop serum nAbs after subcutaneous immunization with BG505.664 SOSIP and 3M-052 adjuvant, which is a TLR7/8 agonist. The neutralization of autologous tier 2 BG505 T332N pseudovirus by the IgA and IgG preparations was measured using the TZM-bl assay. Anti-SOSIP binding antibodies (bAbs) were measured by ELISA. Results: The IgG samples were found to have significantly greater levels of both nAb and bAb. However, after normalizing the nAb titer relative to the concentration of bAb, SOSIP-specific IgA purified from 2/6 animals was found to neutralize just as effectively as SOSIP-specific IgG, and in 3/6 animals, neutralization by the specific IgA was significantly greater. The more potent neutralization by IgA in these three animals was associated with a higher percentage of anti-SOSIP J chain-bound (polymeric) antibody. Conclusions: The parenteral vaccination of nonhuman primates with BG505.664 SOSIP generates HIV-1 tier 2 IgA nAbs in serum, including SOSIP-specific polymeric IgA, which appears to neutralize more efficiently than monomeric IgA or IgG. Mucosal delivery of this SOSIP or other stable Env trimers could generate locally synthesized polymeric IgA nAbs in mucosal tissues and secretions. [ABSTRACT FROM AUTHOR]

This study quantitatively and qualitatively examined the prevalence, frequency, and content of discrimination exposure among gay, bisexual, and other sexually minoritized men (SMM) within sexual minority contexts. Participants were an online, U.S. national sample of 14,133 SMM who reported discrimination exposure within sexual minority contexts targeting: body type, race, sexual behavior, HIV status, gender expression, age, and income/employment. Quantitative analyses included prevalence percentages and frequencies and ANOVAs, t-tests, and correlations to examine the frequency of discrimination exposure type across participant race/ethnicity, sexual identity, gender identity, HIV status, age, and income. Qualitative analyses included conventional content analysis of responses to an open-ended discrimination exposure item. Results showed that discrimination exposure was nearly universal (99%). Discrimination exposure frequency was lowest among White men and, other than for income/employment discrimination exposure, highest among Asian/Pacific Islander men. For several discrimination types, exposure frequency was highest among groups targeted by group-specific negative stereotypes (e.g., Black men were exposed to the most income/employment discrimination). Qualitative analyses highlighted specific exposures to discrimination targeting body type, race/ethnicity, gender identity, attractiveness, education, and intersections between forms of discrimination. Over 69% of write-in responses were relevant to online/app-based discrimination. Findings underscore the importance of examining individual and intersectional discrimination exposure targeting marginalized social positions within sexual minority communities, particularly in online/app contexts. [ABSTRACT FROM AUTHOR]

While human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) researchers have made remarkable strides in the treatment, management, and prevention of HIV/AIDS, one area of research related to HIV/AIDS remains woefully underrepresented in the scientific literature: suicide prevention. The risk of death by suicide among people living with HIV/AIDS (PLWHA) is 100 times higher compared with that among the general population, and the lifetime prevalence of suicide attempts is similarly elevated. Though there have been many suicide prevention studies worldwide and effective interventions have been identified, few prevention strategies have been tested and implemented among PLWHA. A preliminary review of articles published since 2018 revealed only two behavioral interventions designed to address suicide risk in PLWHA, neither of which were based in the United States. No systematic reviews of behavioral interventions for suicide prevention among PLWHA have been published. In this commentary, we call for research to evaluate the effectiveness of suicide prevention interventions and policies that could decrease suicide rates among PLWHA. [ABSTRACT FROM AUTHOR]

: Introduction: Youth under the age of 25 are at high risk for HIV infection. While pre‐exposure prophylaxis (PrEP) has the potential to curb new infections within this population, it is unclear how country‐specific laws and policies that govern youth access to sexual and reproductive health (SRH) services impact access to PrEP. The purpose of this review was to analyse laws and policies concerning PrEP implementation and SRH services available to youth in countries with a high HIV incidence. To the best of our knowledge this is the first systematic assessment of country‐level policies that impact the availability of PrEP to adolescent populations. Methods: We conducted a review of national policies published on or before 12 June 2018 that could impact adolescents’ access to PrEP, SRH services and ability to consent to medical intervention. Countries were included if: (1) there was a high incidence of HIV; (2) they had active PrEP trials or PrEP was available for distribution; (3) information regarding PrEP guidelines were publicly available. We also included a selected number of countries with lower adolescent HIV incidence. Internet and legal database searches were used to identify policies relevant to adolescent PrEP (e.g. age of consent to HIV testing). Results and Discussion: Fifteen countries were selected for inclusion in this review. Countries varied considerably in their respective laws and policies governing adolescents’ access to PrEP, HIV testing and SRH services. Six countries had specific polices around the provision of PrEP to youth under the age of 18. Five countries required people to be 18 years or older to access HIV testing, and six countries had specific laws addressing adolescent consent for‐ and access to‐ contraceptives. Conclusions: Adolescents’ access to PrEP without parental consent remains limited or uncertain in many countries where this biomedical intervention is needed. Observational and qualitative studies are needed to determine if and how adolescent consent laws are followed in relation to adolescent PrEP provisions. Intensified efforts to amend laws that limit adolescent access to PrEP and restrict the establishment of national guidelines supporting adolescent PrEP are also needed to address the epidemic in this group., Introduction Globally, young people (defined by the World Health Organization (WHO) as people aged 10 to 24 years) and adolescents (defined as people aged 10 to 19 years) continue to [...]

New modalities of Pre-exposure Prophylaxis (PrEP) such as long-acting injectable PrEP (LAI-PrEP) promise increased prevention of HIV transmission; however, similar biomedical interventions have not been met with universal adoption by healthcare providers or populations most affected by HIV. This qualitative study explores healthcare provider considerations for the rollout of LAI-PrEP. Eleven key-informant in-depth interviews were conducted with clinicians who prescribe daily oral PrEP. Participants reviewed a currently proposed LAI regimen and were asked to reflect on its implications for their clinical practice. Interviews were transcribed verbatim and thematically coded, with results organized using the Consolidated Framework for Implementation Research (CFIR). All participants expressed interest in prescribing LAI-PrEP and anticipated that at least some patients would be interested. Participants identified characteristics of the intervention, inner intervention setting, and outer intervention setting that will be influential in bringing LAI-PrEP to scale. Clinicians in the South have unique insights into the challenges of and opportunities for successful rollout of future PrEP regimens. Bringing these insights into a CFIR framework highlights the nuances surrounding LAI-PrEP, including structural concerns such as cost barriers and access to in-person healthcare services. It is critical to address these challenges to ensure successful implementation of new PrEP formulations. [ABSTRACT FROM AUTHOR]