CHRP Research Results Spotlight
research results: Highlights from chrp emergency seed funding grants for sars-cov-2
- The UCSC SARS-CoV-2 Genome Browser, an interactive web-based tool for sharing molecular data
Max Haeussler and colleagues used their RGPO Emergency Seed Funding Award to create this tool, enabling researchers around the globe to rapidly post and cross-reference their molecular data about the SARS-CoV-2 genome. Their work was published in Nature Genetics.
- Geospatial distribution of COVID-19 in California shifted to African-American communities after 100 days
- Los Angeles Neighborhoods and COVID-19 Medical Vulnerability Indicators: A Local Data Model for Equity in Public Health Decision-Making
- CHRP-funded innovation uses nanoparticles for simpler, faster SARS-CoV-2 assays and at-home test kits
- Mitigating the synergistic epidemics of homelessness and COVID-19
- UC Berkeley and Berkeley National Lab create structural map of SARS-CoV-2 protein
- Rural areas of the U.S. may not have engaged with COVID-19 topics on social media until later stages of the outbreak; geospatial analysis of Twitter messages offers lessons for pandemic communication
Pseudouridylation of 7SK snRNA promotes 7SK snRNP formation to suppress HIV-1 transcription and escape from latency
CHRP Research Read: Full article available at the following link:
The Impact Of Medicaid Expansion On People Living With HIV And Seeking Behavioral Health Services
CHRP supported researchers explore how Medicaid expansion influenced people living with HIV utilization of behavioral health services in California. Learn more here: https://escholarship.org/uc/item/2st6f8c9
Exploring the preferences of a culturally congruent, peer-based HIV prevention intervention for black men who have sex with men
Want to learn more about barriers and motivators for HIV testing and treatment adherence among Black men who have sex with men in California? Read about this CHRP supported research at the following link: https://escholarship.org/uc/item/9rs438zm#main
SMAC Mimetics Induce Autophagy-Dependent Apoptosis of HIV-1-Infected Resting Memory CD4+ T Cells
CHRP supported researchers find that DIABLO/SMAC mimetics selectively kill HIV-CD4+ T cells without increasing virus production or targeting uninfected CD4+ T cells. Read the article outlining their research by clicking the following link: https://escholarship.org/uc/item/8r2087xr#main
PrEP Uptake, Adherence, and Discontinuation among California YMSM Using Geosocial Networking Applications
CHRP supported researchers explore PrEP use in young men who have sex with men. What role might geosocial networking play in uptake and adherence? Check out the research findings by clicking on the link:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5140696/
TransPrEP! Project: HIV Prevention by and for the Transgender Community in California
TransPrEP! is a short video about three research projects in California, sponsored by the California HIV/AIDS Research Program. The video premiered at the Opening Plenary of the National Transgender Health Summit in Oakland, California on 11th November 2017. Video available here.
Induction of autophagy by PI3K/MTOR and PI3K/MTOR/BRD4 inhibitors suppresses HIV-1 replication
This team works with a new class of drugs that shows potential to control HIV infection, and here they show that the treatment works by decreasing HIV replication in macrophages. Learn more here: https://escholarship.org/uc/item/1gp201vf
Using a Social Network Strategy to Distribute HIV Self-Test Kits to African American and Latino MSM
Research Highlight: HIV self-test kits distributed through social network strategies could be used to increase HIV testing uptake and reduce the number of individuals unaware of their HIV status. Learn more about the research here: https://escholarship.org/uc/item/8704d087
Flow Cytometric Analysis of HIV-1 Transcriptional Activity in Response to shRNA Knockdown in A2 and A72 J-Lat Cell Lines
Small-molecule bromodomain and extraterminal (BET) inhibitors can reverse HIV viral latency in some models. To figure out how they do this, this team utilized small hairpin RNAs (shRNAs) that target specialized proteins, and measured transcriptional activation of the HIV-1 LTR upon shRNA knockdown. Read the full article here: https://escholarship.org/uc/item/5nw465x5
Host Methyltransferases and Demethylases: Potential New Epigenetic Targets for HIV Cure Strategies and Beyond
Epigenetic regulation of DNA may be useful as part of HIV cure strategies. This team describes how methylation-modifying agents can be used in a strategy of epigenetic regulation to purge the viral reservoir or silence viral transcription. Read the full article here: https://escholarship.org/uc/item/1sm78685
Flow Cytometric Analysis of Drug-induced HIV-1 Transcriptional Activity in A2 and A72 J-Lat Cell Lines
CHRP Research Read: How to use flow cytometry to quantify transcriptional activation of the HIV-1 long terminal repeat (LTR) during antiretroviral therapy, using latently HIV-1-infected Jurkat (J-Lat) cell lines that contain a GFP cassette reporter instead of Luciferase. https://escholarship.org/uc/item/5r62354b
‘I am not a man’: Trans-specific barriers and facilitators to PrEP acceptability among transgender women
A DEAD-box protein acts through RNA to promote HIV-1 Rev-RRE assembly
Using single-molecule fluorescence, this CHRP-funded scientist is working to find small molecules that could interfere with HIV replication. Here his team shows how one host protein acts like a chaperone for one of HIV’s proteins. Read the full article for free here: https://escholarship.org/uc/item/93f085c0
Dynamic conformational changes in the rhesus TRIM5αdimer dictate the potency of HIV-1 restriction
A CHRP-supported researcher and their colleagues find that elements within the Linker 2 region influence the potency of HIV restriction. Read the full article published in Virology here: https://escholarship.org/uc/item/2595k8wg
Patients' Perceptions and Experiences of Shared Decision-Making in Primary HIV Care Clinics
This qualitative paper out of one of our California HIV/AIDS Policy Research Centers explores the role of shared decision-making in HIV care. Read the full article here to explore important barriers and facilitators to shared decision-making in this context: https://escholarship.org/uc/item/8vh8j5w4
Community member perspectives from transgender women and men who have sex with men on pre-exposure prophylaxis as an HIV prevention strategy: Implications for implementation
CHRP grantee publication throwback Thursday: This 2012 qualitative study identified three main themes among MSM and transgender women regarding their perspective about PrEP uptake. Would be interesting to know how these perspectives have changed over the last 5 years. Read the full article here: https://escholarship.org/uc/item/7x81h91p
Coexistence of potent HIV-1 broadly neutralizing antibodies and antibody-sensitive viruses in a viremic controller
Three HIV-1 antibodies are isolated from a donor who has controlled HIV for years without ART, and they are shown to control HIV infection in an animal model. Broadly neutralizing antibodies (bNAbs) such as these are being tested as new HIV prevention and treatment options. CHRP supported one of the investigators, and the results are published in the journal Science Translational Medicine. Full text here: http://escholarship.org/uc/item/59f916pg
Structural basis for germline antibody recognition of HIV-1 immunogens
Results of a pilot study at UCSF show that microbial transplants for persons living with HIV are well tolerated and may be useful to treat systemic inflammation. HIV can alter the flora found in the gut. This treatment is being tested as a way to reconstitute the gut microbiome, and in turn treat systemic immune activation, which is increased during HIV disease. CHRP funded one of the investigators. The full article is available here: http://escholarship.org/uc/item/0b44p24g
A New Glycan-Dependent CD4-Binding Site Neutralizing Antibody Exerts Pressure on HIV-1 In Vivo
Using blood samples from HIV-positive donors who have potent neutralizing antibodies (bNAbs), these researchers discovered a new antibody, and went on to show that it combats HIV. CHRP supported one of the investigators, and the results are published in the open access journal PloS Pathogens. Full article available here: http://escholarship.org/uc/item/3f31r61s
Structural basis for germline antibody recognition of HIV-1 immunogens
Using x-ray crystallography, researchers have discovered how a group of broadly neutralizing antibodies (bNAbs) might be triggered by a vaccine to combat HIV infection. CHRP supported one of the investigators. Full article, published in eLife,is available here: http://escholarship.org/uc/item/0388p0x6
Potent and Targeted Activation of Latent HIV-1 Using the CRISPR/dCas9 Activator Complex
Researchers used state-of-the-art gene editing technology (CRISPR/dCas9) to target a "hotspot" in the HIV genome, and showed that this system could be used toward a functional cure of HIV. CHRP supported one of the investigators, and the results are published in Molecular Therapy. Full article available here: http://escholarship.org/uc/item/4vn8h1pd
Antibody engineering for increased potency, breadth and half-life
Scientists can now create antibodies to prevent or treat multiple diseases. This team of researchers reviewed the state of the art of engineering highly potent antibodies for HIV treatment, and explains challenges in the field. CHRP supported one of the investigators, and the results are published in the journal Current Opinion in HIV and AIDS. Full article here: http://escholarship.org/uc/item/5t39h737#page-1
The Role of Bromodomain Proteins in HIV Latency
A CHRP-funded investigator, Daniela Boehm, at The Gladstone Institutes has discovered a strategy for therapeutic targeting of latent HIV. Her team shows that blocking an enzyme called SMYD2 could work as the "shock" part of a "shock and kill" approach to an HIV cure. This highly significant work bridges both HIV and cancer treatment innovation -- the same target she discovered can be used for both diseases. Read the full article here: http://escholarship.org/uc/item/9ng6s9hf#
LONGITUDINAL IMAGING OF HIV-1 SPREAD
CHRP-funded research team at CalTech captures sequential photos of acute HIV infection spreading in tissues, using new 3D microscope technique. “Thousands of virions released by individual cells” reveal peak infectivity of virus in the gut at times when virus in the blood was barely detectable. Follow the links to read the article and to view the videos that bring the story to life by showing where the cells live in the tissues, and what the virus looks like when it’s budding versus at peak infectivity: http://escholarship.org/uc/item/4r94z1vg
HIV CRIMINALIZATION IN CALIFORNIA
California has five HIV-related laws that criminalize a range of activities – from engaging in condomless sex without disclosure with the intent of transmitting HIV to donating bodily fluids or organs while aware of ones HIV-positive status – regardless of if transmission occurred. Grantees from the California HIV/AIDS Policy Center set out to gain a better understanding of the use and enforcement of these laws. They found that between 1988 and 2014, 800 individuals in California were arrested or cited under an HIV-related criminal code. Black and Latino individuals accounted for 67% of these cases and 43% were women, though these groups only account for 51% and 13% of people living with HIV in California, respectively. Almost all (95%) of these individuals were engaged or believed to be engaged in sex work. While only 31% of arrests or citations resulted in HIV-related charges being brought against the individual, all but one of those charges resulted in conviction. White men were much less likely to be charged. Future research is needed to better understand the disparities in the enforcement of these laws within California.
INSURANCE COVERAGE FOR PLWH
Food Insecurity and HIV
Understanding the structural factors that contribute to increased risk of HIV infection and poorer outcomes for those living with HIV is essential as we work to curb the epidemic here in California. One of our grantees, Dr. Sheri Weiser of UC San Francisco, did some pioneering work in this arena, with a focus on food insecurity. She found that homeless people living with HIV (PLWH) who also experienced food insecurity had poorer treatment adherence, were less likely to be virally suppressed, and had lower CD4 counts compared to homeless PLWH who did not experience food insecurity. Her work also found significant associations between food insecurity and HIV risk behaviors among PLWH – those who experienced food insecurity had more unprotected sex, more sex partners, and increased use of illicit drugs compared to PLWH who did not experience food insecurity. HIV treatment programs need to integrate ways to address food insecurity in their programming for treatment efforts to be sustainable and effective. (Weiser, ID08-SF-054)
HIV and mental illness
Individuals with bipoloar disorder who are also living with HIV are at increased risk for poor medication adherence. One of our grantees, Dr. David Moore of UC San Diego, developed a text messaging reminder system (iTAB) to improve medication adherence in this population –for both anti-psychotic and HIV meds. He found that individuals in the text message reminder arm had significantly better adherence for both types of medication (compared to the control arm). The intervention also helped decrease variability in the time of day people took their medications. Dr. Moore’s work didn’t stop there. He is now working on applying his customizable text messaging reminder system to other populations at risk, and his CHRP-funded research has led to the award of an NIH grant. For this grant, the original iTAB system was modified and transformed into one that was targeted for a new demographic: HIV+/Methamphetamine dependent individuals. The texting for adherence model is also serving as the basis for another CHRP-funded project: a text message intervention for adherence among HIV-uninfected individuals using Pre-Exposure Prophylaxis as HIV prevention. (Moore, ID09-SD-047)
HIV and Incarceration
Incarcerated individuals have competing priorities once released. These include substance abuse treatment, finding housing, getting financial assistance, and re-establishing personal connections in their communities. Ensuring they have access to HIV treatment may not come high on that list. Dr. Maria Luisa Zuniga of UC San Diego set out to explore what happens to access to treatment among people living with HIV (PLWH) once released from jail or prison. She found that among individuals who were able to adhere consistently upon their release cited having extra doses available at their homes, receiving assistance from a case manager, and having made adherence a personal priority. Individuals unable to maintain adherence upon release cited not possessing extra doses or inability to pay for medication as reasons for non-adherence. Future interventions are needed to ensure PLWH being released from prison or jail can maintain or re-engage in effective HIV care and treatment programs – reducing the burden of HIV treatment on their list of competing priorities. (Zuniga, ID09-SD-016)
Water in gay bars as HIV prevention tool?
Can improving access to water in bars and providing patrons with blood alcohol level information decrease alcohol consumption and impact alcohol-associated HIV risks? Edwin Charlebois and his research team set out to answer this question. They knew that gay bar patrons are at higher risk for alcohol associated HIV risks, and drinking water in bars is one commonly used way to decrease alcohol consumption. But water is not always easily accessible in bars – so this team of researchers decided to develop and test an intervention to change that. At selected gay bars the team installed a free, self-service filtered water dispenser to help bar patrons pace their alcohol use. They also provided those leaving the bar with the option of having their blood alcohol levels measured and seeing how their levels compared to others exiting the bar. What they found was that most men in their sample were at high risk for HIV and about a third reported that alcohol use affected their condom use decisions. Most men they interacted with found the breathalyzer acceptable and liked hearing how their blood alcohol levels compared to others. The researchers also looked at other bar-related factors that contributed to increased alcohol intake – they found that the strength of the drinks served (more alcohol by volume in gay bars than other bars) and discounted drink sales (more frequent in gay bars) both resulted in patrons drinking more alcohol. The research team received an NIH grant to expand this study, and early results from that work showed a significant reduction in alcohol consumption in the intervention bars compared to control bars. The researchers suggest this as a feasible intervention to reduce blood alcohol concentration alcohol-associated HIV risk among gay bar patrons. (5R21AA020467-02).
Community Viral Load
Das-Douglas’ team set out to see if they could use measures of HIV viral load at the community level (CVL) to explain changes in the number of new HIV infections in San Francisco. They knew that more people on treatment would lead to more people being virally suppressed, which in turn would lower the overall viral load at the community level. They found that decreases in annual CVL measures in San Francisco were significantly associated with decreases in the number of new HIV diagnoses over time, and accompanied by a decline in estimated HIV incidence by over one-third from 2006–2008. Declines in CVL in San Francisco coincided with an increase in ART uptake among people living with AIDS, availability of more effective, potent, and tolerable ART regimens, and a significant increase in the population rate of virologic suppression. Declines were also concurrent with changes in laws and policy initiatives facilitating HIV testing, increasing acute HIV detection, improvements in partner services, and a reduction in the rate of unknown HIV infection. The team’s findings support the notion that reductions in CVL can in turn reduce HIV incidence at the population level. Not only that, their results also support the use of CVL as a surveillance measure for treatment effectiveness and HIV transmission risk in a given jurisdiction. They also note that geographic mapping of CVL levels could help identify “hotspots” or disparities, allowing more targeted interventions. The researchers recommend using CVL as an indicator of the overall success of ART uptake and for HIV prevention efforts, an indicator that will significantly help us evaluate “getting to zero” efforts across California. See the team’s full results here.