California HIV/AIDS Research Program Funded Publications

Since its founding in 1983 by California State Legislature, the California HIV/AIDS Research Program (CHRP) has supported excellent, timely, and innovative research that is attentive to the needs of California, accelerating progress towards prevention, care and treatment for HIV/AIDS. During this time over $250M has been awarded for over 2,000 research projects.

CHRP provides start-up funds for the development of cutting edge research in California, providing critical leverage to bring in federal and private dollars to the state. A 2006 survey of California investigators found that more than five dollars in federal and other grant support was generated for every dollar invested by CHRP in California-based research.

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Cover page of Type 1 Human Immunodeficiency Virus (HIV-1) Incidence, Adherence, and Drug Resistance in Individuals Taking Daily Emtricitabine/Tenofovir Disoproxil Fumarate for HIV-1 Pre-exposure Prophylaxis: Pooled Analysis From 72 Global Studies

Type 1 Human Immunodeficiency Virus (HIV-1) Incidence, Adherence, and Drug Resistance in Individuals Taking Daily Emtricitabine/Tenofovir Disoproxil Fumarate for HIV-1 Pre-exposure Prophylaxis: Pooled Analysis From 72 Global Studies

(2024)

Background

Oral pre-exposure prophylaxis (PrEP) with emtricitabine/tenofovir disoproxil fumarate (F/TDF) has high efficacy against HIV-1 acquisition. Seventy-two prospective studies of daily oral F/TDF PrEP were conducted to evaluate HIV-1 incidence, drug resistance, adherence, and bone and renal safety in diverse settings.

Methods

HIV-1 incidence was calculated from incident HIV-1 diagnoses after PrEP initiation and within 60 days of discontinuation. Tenofovir concentrations in dried blood spots (DBS), drug resistance, and bone/renal safety indicators were evaluated in a subset of studies.

Results

Among 17 274 participants, there were 101 cases with new HIV-1 diagnosis (.77 per 100 person-years; 95% confidence interval [CI]: .63-.94). In 78 cases with resistance data, 18 (23%) had M184I or V, 1 (1.3%) had K65R, and 3 (3.8%) had both mutations. In 54 cases with tenofovir concentration data from DBS, 45 (83.3%), 2 (3.7%), 6 (11.1%), and 1 (1.9%) had average adherence of <2, 2-3, 4-6, and ≥7 doses/wk, respectively, and the corresponding incidence was 3.9 (95% CI: 2.9-5.3), .24 (.060-.95), .27 (.12-.60), and .054 (.008-.38) per 100 person-years. Adherence was low in younger participants, Hispanic/Latinx and Black participants, cisgender women, and transgender women. Bone and renal adverse event incidence rates were 0.69 and 11.8 per 100 person-years, respectively, consistent with previous reports.

Conclusions

Leveraging the largest pooled analysis of global PrEP studies to date, we demonstrate that F/TDF is safe and highly effective, even with less than daily dosing, in diverse clinical settings, geographies, populations, and routes of HIV-1 exposure.

Cover page of A Mixed Methods Evaluation of Pharmacists' Readiness to Provide Long-Acting Injectable HIV Pre-exposure Prophylaxis in California

A Mixed Methods Evaluation of Pharmacists' Readiness to Provide Long-Acting Injectable HIV Pre-exposure Prophylaxis in California

(2024)

Background

Pre-exposure prophylaxis (PrEP) uptake remains low among people who could benefit, some of whom may prefer alternatives to oral PrEP, such as long-acting injectable pre-exposure prophylaxis (LAI-PrEP). We evaluated the potential for LAI-PrEP provision in pharmacies through a mixed methods study of pharmacists in California, where Senate Bill 159 enables pharmacists to independently provide oral PrEP.

Methods

In 2022-2023, we conducted an online cross-sectional survey of California pharmacists and pharmacy students (n = 919) and in-depth interviews with pharmacists (n = 30), both of which included modules assessing attitudes about PrEP provision. Using log-binomial regression, we estimated prevalence ratios (PRs) comparing survey participants' willingness to provide LAI-PrEP by pharmacy- and individual-level characteristics. Qualitative interview data were analyzed using Rapid Qualitative Analysis to identify factors that may affect pharmacists' provision of LAI-PrEP.

Results

Half of the survey participants (53%) indicated that they would be willing to administer LAI-PrEP using gluteal injection in their pharmacy. Willingness was higher among participants who worked in pharmacies that provided vaccinations or other injections (56% vs. 46%; PR: 1.2; 95% confidence interval: 1.0-1.4) and/or oral PrEP under Senate Bill 159 (65% vs. 51%; PR: 1.3; 95% confidence interval: 1.1-1.5) than among participants whose pharmacies did not. Interviewed participants reported barriers to LAI-PrEP provision, including the need for increased training and staffing, a private room for gluteal injections, better medication access, and payment for services.

Conclusion

Pharmacies offer a promising setting for increased LAI-PrEP access. However, pharmacists may require additional training, resources, and policy changes to make implementation feasible.

Managing HIV During the COVID-19 Pandemic: A Study of Help-Seeking Behaviors on a Social Media Forum

(2024)

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.

Cover page of Facilitators of PrEP Persistence among Black and Latinx Transgender Women in a PrEP Demonstration Project in Southern California

Facilitators of PrEP Persistence among Black and Latinx Transgender Women in a PrEP Demonstration Project in Southern California

(2024)

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.

The impact of intimate partner violence on PrEP adherence among U.S. Cisgender women at risk for HIV

(2024)

Background

Cisgender women account for 1 in 5 new HIV infections in the United States, yet remain under-engaged in HIV prevention. Women experiencing violence face risk for HIV due to biological and behavioral mechanisms, and barriers to prevention, such as challenges to Pre-Exposure Prophylaxis for HIV Prevention (PrEP) adherence. In this analysis, we aim to characterize intimate partner violence (IPV) among cisgender heterosexual women enrolled in a PrEP demonstration project and assess the associations with PrEP adherence.

Methods

Adherence Enhancement Guided by Individualized Texting and Drug Levels (AEGiS) was a 48-week single-arm open-label study of PrEP adherence in HIV-negative cisgender women in Southern California (N = 130) offered daily tenofovir disoproxil fumarate/emtricitabine (TDF/FTC). From 6/2016 to 10/2018, women completed a survey reporting HIV risk behavior and experiences of any IPV (past 90-days) and IPV sub-types (past-year, lifetime) and biological testing for HIV/STIs at baseline, and concentrations of tenofovir-diphosphate (TFV-DP) in dried blood spots at weeks 4, 12, 24, 36, and 48. Outcomes were TFV-DP concentrations consistent with ≥ 4 or ≥ 6 doses/week at one or multiple visits. Multivariable logistic regression models were conducted to examine associations.

Results

Past-90-day IPV was reported by 34.4% of participants, and past-year and lifetime subtypes reported by 11.5-41.5%, and 21.5-52.3%, respectively. Women who engaged in sex work and Black women were significantly more likely to report IPV than others. Lifetime physical IPV was negatively associated with adherence at ≥ 4 doses/week at ≥ 3 of 5 visits, while other relationships with any IPV and IPV sub-types were variable.

Conclusion

IPV is an indication for PrEP and important indicator of HIV risk; our findings suggest that physical IPV may also negatively impact long-term PrEP adherence.

Clinical trials registration

NCT02584140 (ClinicalTrials.gov), registered 15/10/2015.

Cover page of Determinants of HIV Pre-Exposure Prophylaxis (PrEP) Retention among Transgender Women: A Sequential, Explanatory Mixed Methods Study

Determinants of HIV Pre-Exposure Prophylaxis (PrEP) Retention among Transgender Women: A Sequential, Explanatory Mixed Methods Study

(2024)

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.

Targeting host deoxycytidine kinase mitigates Staphylococcus aureus abscess formation

(2023)

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.

Drug Use, Family Support, and Depressive Symptoms Among Latinx Sexual Minority Men: A Longitudinal Analysis

(2023)

Family rejection has negative health consequences for Latinx sexual minority men (LSMM). However, LSMM often reconcile with their families, a phenomenon cross-sectional studies miss. We analyzed longitudinal data from the Healthy Young Men's Study in Los Angeles. We used individual fixed-effects Poisson regression to model changes over time in the associations among family support, drug use, and depressive symptoms. We found that (1) the initiation of drug use was associated with a 7.2% (Ratio=1.072, 95% CI 1.006 - 1.142, p = 0.03) increase in family support among LSMM who reported high depressive symptoms (depression subscale T-score ≥ 63) in at least one data wave; (2) a 1-unit increase in family support was associated with a 4.7% (RR = ;0.953, 95% CI 0.931 - 0.976, p < 0.001) decrease in the probability of high depressive symptoms; and (3) no significant association between a change in drug use and a change in high depressive symptoms. Over time, LSMM appear to benefit from the health effects of family support associated with Latinx family structures.

Cover page of Impact of post-incarceration care engagement interventions on HIV transmission among young Black men who have sex with men and their sexual partners: an agent-based network modeling study

Impact of post-incarceration care engagement interventions on HIV transmission among young Black men who have sex with men and their sexual partners: an agent-based network modeling study

(2023)

Background

Understanding the impact of incarceration on HIV transmission among Black men who have sex with men is important given their disproportionate representation among people experiencing incarceration and the potential impact of incarceration on social and sexual networks, employment, housing, and medical care. We developed an agent-based network model (ABNM) of 10,000 agents representing young Black men who have sex with men in the city of Chicago to examine the impact of varying degrees of post-incarceration care disruption and care engagement interventions following release from jail on HIV incidence.

Methods

Exponential random graph models were used to model network formation and dissolution dynamics, and network dynamics and HIV care continuum engagement were varied according to incarceration status. Hypothetical interventions to improve post-release engagement in HIV care for individuals with incarceration (e.g., enhanced case management, linkage to housing and employment services) were compared to a control scenario with no change in HIV care engagement after release.

Finding

HIV incidence at 10 years was 4.98 [95% simulation interval (SI): 4.87, 5.09 per 100 person-years (py)] in the model population overall; 5.58 (95% SI 5.38, 5.76 per 100 py) among those with history of incarceration, and 12.86 (95% SI 11.89, 13.73 per 100 py) among partners of agents recently released from incarceration. Sustained post-release HIV care for agents with HIV and experiencing recent incarceration resulted in a 46% reduction in HIV incidence among post-incarceration partners [incidence rate (IR) per 100 py = 5.72 (95% SI 5.19, 6.27) vs. 10.61 (95% SI 10.09, 11.24); incidence rate ratio (IRR) = 0.54; (95% SI 0.48, 0.60)] and a 19% reduction in HIV incidence in the population overall [(IR per 100 py = 3.89 (95% SI 3.81-3.99) vs. 4.83 (95% SI 4.73, 4.92); IRR = 0.81 (95% SI 0.78, 0.83)] compared to a scenario with no change in HIV care engagement from pre-to post-release.

Interpretation

Developing effective and scalable interventions to increase HIV care engagement among individuals experiencing recent incarceration and their sexual partners is needed to reduce HIV transmission among Black men who have sex with men.

Funding

This work was supported by the following grants from the National Institutes of Health: R01DA039934; P20 GM 130414; P30 AI 042853; P30MH058107; T32 DA 043469; U2C DA050098 and the California HIV/AIDS Research Program: OS17-LA-003; H21PC3466.

Cover page of Relating ‘to her Human Side’: a Grounded Theory analysis of cosmetologists’ and aestheticians’ relationships with clients in Black American beauty salons to inform sexual health interventions

Relating ‘to her Human Side’: a Grounded Theory analysis of cosmetologists’ and aestheticians’ relationships with clients in Black American beauty salons to inform sexual health interventions

(2023)

Due to the elevated incidence of HIV among Black American women, effective sexual health interventions are needed. To explore beauty salons as settings for such interventions, we examined Black American women stylists' experiences discussing sex-related topics with Black American women clients. Constructivist Grounded Theory methodology guided data collection and analysis. Individual intensive interviews were conducted in 2019 with 16 Black women cosmetologists and/or aestheticians who served Black women in Southern California. Analyses generated grounded theory which we refer to as Relating 'to her Human Side': Black American cosmetologist-client relationship building model. The model highlights the importance of three sets of practices: 1) playing different roles to appeal to clients' varying wants and needs, 2) creating a comfortable atmosphere, and 3) establishing a judgement-free zone. Stylists put clients at ease and consequently, clients shared stories regarding sex and relationships freely. Stylists' actions built trusting relationships with clients, thus crafting beauty salons as atmospheres favourable for sex-related conversations and potential sexual health interventions.

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