California HIV/AIDS Research Program

Sexual and gender minority youth (SGMY) are vulnerable to acquiring HIV and need HIV prevention and health services, but may have competing needs. A prior analysis found that PrEP use reports increased in a combination intervention study arm with coaching, peer support, and automated text-messages. This paper examines ancillary support and healthcare services utilization as secondary intervention objectives. SGMY (N = 895, 40% Black, 29% Latino) in Los Angeles and New Orleans were recruited from May, 2017 to August, 2019 and randomized to four intervention conditions: (a) automated text-messaging and monitoring intervention (AMMI), (b) AMMI plus peer support online (AMMI+PS), (c) AMMI plus strengths-based coaching by near-peer paraprofessionals (AMMI+C), or (d) all three (AMMI+PS+C). Intent-to-treat multivariate regression analyses evaluated the interventions efficacy on past 4-month reports of ancillary support services use, having a regular healthcare provider, receiving care from doctors office or clinic and mental health specialists, and participation in mental health support groups and HIV prevention programs. Ancillary services utilization reports declined from 40% of youth reporting an average of 4.4 services at baseline to 22.6% reporting 2.5 services by 24 months. Food, housing, transportation, and other basic services were utilized most frequently. Youth in the two coaching interventions maintained higher reports of services use over time compared to AMMI-only (both OR 1.23, 95%CI 1.12-1.35) and to AMMI+PS (both OR 1.20 95%CI 1.08-1.33). Our coaching intervention may support SGMY to stay engaged in support services. Results may be limited by self-report biases. It is unclear if these services are related to better long-term outcomes.

Sexual and gender minority youth (SGMY) are vulnerable to acquiring HIV and need HIV prevention and health services, but may have competing needs. A prior analysis found that PrEP use reports increased in a combination intervention study arm with coaching, peer support, and automated text-messages. This paper examines ancillary support and healthcare services utilization as secondary intervention objectives. SGMY (N = 895, 40% Black, 29% Latino) in Los Angeles and New Orleans were recruited from May, 2017 to August, 2019 and randomized to four intervention conditions: (a) automated text-messaging and monitoring intervention (AMMI), (b) AMMI plus peer support online (AMMI+PS), (c) AMMI plus strengths-based coaching by near-peer paraprofessionals (AMMI+C), or (d) all three (AMMI+PS+C). Intent-to-treat multivariate regression analyses evaluated the interventions' efficacy on past 4-month reports of ancillary support services use, having a regular healthcare provider, receiving care from doctor's office or clinic and mental health specialists, and participation in mental health support groups and HIV prevention programs. Ancillary services utilization reports declined from 40% of youth reporting an average of 4.4 services at baseline to 22.6% reporting 2.5 services by 24 months. Food, housing, transportation, and other basic services were utilized most frequently. Youth in the two coaching interventions maintained higher reports of services use over time compared to AMMI-only (both OR 1.23, 95%CI 1.12-1.35) and to AMMI+PS (both OR 1.20 95%CI 1.08-1.33). Our coaching intervention may support SGMY to stay engaged in support services. Results may be limited by self-report biases. It is unclear if these services are related to better long-term outcomes.

Combining a T cell-targeting mRNA vaccine encoding the conserved SARS-CoV-2 RNA-dependent RNA polymerase, RdRp, with a Spike-encoding mRNA vaccine may offer an additional pathway toward COVID-19 protection. Here, we show that a nucleoside-modified RdRp mRNA vaccine raises robust and durable CD8+ T cell responses in mice. Immunization drives a CD8+ T cell response enriched toward a specific RdRp epitope. Unexpectedly, coadministration of mRNA vaccines encoding RdRp or the Spike Receptor Binding Domain (RBD) dampens RBD-specific immune responses. Contralateral administration reduces the suppression of RBD-specific T cell responses while type I interferon signaling blockade restores RBD-specific antibodies. A staggered immunization strategy maintains both RBD vaccine-mediated antibody and T cell responses as well as protection against lethal SARS-CoV-2 challenge in human ACE2 transgenic mice. In HLA-A2.1 transgenic mice, the RdRp vaccine elicits CD8+ T cell responses against HLA-A*02:01-restricted epitopes recognized by human donor T cells. These results highlight RdRp as a candidate antigen for COVID-19 vaccines. The findings also offer insights into crafting effective multivalent mRNA vaccines to broaden CD8+ T cell responses against SARS-CoV-2 and potentially other viruses with pandemic potential.

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Although numerous editorials claim the COVID-19 pandemic has disproportionately impacted vulnerable populations, particularly those affected by HIV, these claims have received limited empirical evaluation. We analyzed posts to Reddit's r/HIVAIDS from January 3, 2012 through April 30, 2022 to (a) assess changes in the volume of posts during the pandemic and (b) determine the needs of HIV affected communities. There were cumulatively 100% (95%CI: 75-126) more posts than expected since the US declared a pandemic emergency. The most prevalent themes in these posts were for obtaining an HIV + diagnosis (representing 34% (95%CI:29-40) of all posts), seeking HIV treatment (20%; 95%CI:16-25), finding psychosocial support (16%; 95%CI:12-20), and tracking disease progression (8%; 95%CI:5-11). Discussions about PrEP and PEP were the least common, representing less than 6% of all posts each. Social media has increasingly become an important health resource for vulnerable populations seeking information, advice, and support. Public health organizations should recognize how the lay public uses social media and collaborate with social media companies to ensure that the needs of help-seekers on these platforms are met.

Black and Latinx transgender women in the United States (U.S.) are at disproportionately high risk for HIV. Although HIV pre-exposure prophylaxis (PrEP) reduces the risk of HIV infection, uptake and persistence (i.e., ability to continue taking PrEP over time) can be a challenge for Black and Latinx transgender women due to myriad social and structural forces. In this qualitative study, we present unique data on the facilitators of PrEP persistence from Black and Latinx transgender women who initiated PrEP and exhibited varying levels of persistence during a demonstration project in Southern California. PrEP persistence was assessed by collecting quantitative intracellular tenofovir-diphosphate (TFV-DP) levels on dried blood spot (DBS) samples collected at weeks 12 and 48. Informed by the socioecological framework, we conducted and analyzed interviews using qualitative content analysis to determine themes on the facilitators of PrEP persistence. Individual-level facilitators included the use of reminders, having high individual-level HIV risk perception, feeling empowered to take PrEP, and reporting having improved peace of mind and mental health because of taking PrEP. Interpersonal/Community-level facilitators included feeling motivation to prevent HIV in the community, motivation to prevent HIV in the context of sex work, and having high community-level risk perception. Structural-level facilitators included having positive experiences in affirming healthcare settings and having PrEP visits combined with other gender-related healthcare visits. Interventions aiming to increase PrEP uptake and persistence among Black and Latinx transgender women in the U.S. should harness the multiple levels of support exhibited by those who were able to start and persist on PrEP in the face of the myriad social and structural barriers.

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Transgender women (TW) face inequities in HIV and unique barriers to PrEP, an effective biomedical intervention to prevent HIV acquisition. To improve PrEP retention among TW, we examined factors related to retention using a two-phase, sequential explanatory mixed methods approach. In Phase I, we used data from a trial of 170 TW who were provided oral PrEP to examine predictors of 24-week retention. In Phase II, we conducted 15 in-depth interviews with PrEP-experienced TW and used thematic analysis to explain Phase I findings. In Phase I, more participants who were not retained at 24 weeks reported sex work engagement (18% versus 7%) and substantial/severe drug use (18% versus 8%). In Phase II, participants reported drug use as a barrier to PrEP, often in the context of sex work, and we identified two subcategories of sex work. TW engaged in "non-survival sex work" had little difficulty staying on PrEP, while those engaged in "survival sex work" struggled to stay on PrEP. In Phase I, fewer participants not retained at 24 weeks reported gender-affirming hormone therapy (GAHT) use (56% versus 71%). In Phase II, participants prioritized medical gender affirmation services over PrEP but also described the bidirectional benefits of accessing GAHT and PrEP. TW who engaged in "survival sex work" experience barriers to PrEP retention (e.g., unstable housing, drug use) and may require additional support to stay in PrEP care.

Host-directed therapy (HDT) is an emerging approach to overcome antimicrobial resistance in pathogenic microorganisms. Specifically, HDT targets host-encoded factors required for pathogen replication and survival without interfering with microbial growth or metabolism, thereby eliminating the risk of resistance development. By applying HDT and a drug repurposing approach, we demonstrate that (R)-DI-87, a clinical-stage anti-cancer drug and potent inhibitor of mammalian deoxycytidine kinase (dCK), mitigates Staphylococcus aureus abscess formation in organ tissues upon invasive bloodstream infection. Mechanistically, (R)-DI-87 shields phagocytes from staphylococcal death-effector deoxyribonucleosides that target dCK and the mammalian purine salvage pathway-apoptosis axis. In this manner, (R)-DI-87-mediated protection of immune cells amplifies macrophage infiltration into deep-seated abscesses, a phenomenon coupled with enhanced pathogen control, ameliorated immunopathology, and reduced disease severity. Thus, pharmaceutical blockade of dCK represents an advanced anti-infective intervention strategy against which staphylococci cannot develop resistance and may help to fight fatal infectious diseases in hospitalized patients.