Lessons From Mass-Testing for Coronavirus Disease 2019 in Long-Term Care Facilities for the Elderly in San Francisco.

Coronavirus disease 2019 can cause significant mortality in the elderly in long-term care facilities (LTCF). We describe 4 LTCF outbreaks where mass testing identified a high proportion of asymptomatic infections (4%-41% in healthcare workers and 20%-75% in residents), indicating that symptom-based screening alone is insufficient for monitoring for COVID-19 transmission.

On-Demand Oral Pre-exposure Prophylaxis with Tenofovir/Emtricitabine: What Every Clinician Needs to Know.

Based on the results of the IPERGAY study, on-demand HIV pre-exposure prophylaxis (PrEP; also known as "non-daily PrEP," "event-driven PrEP," or "2-1-1 PrEP") is being requested more frequently by patients who have intermittent sexual risk or are unable/unwilling to take daily PrEP; therefore, clinicians will be increasingly required to familiarize themselves with its appropriate use. In this perspective, we summarize data related to on-demand PrEP, describe advantages and disadvantages for this alternative dosing strategy, and provide clinical counseling points.

Understanding PrEP Persistence: Provider and Patient Perspectives.

PrEP persistence, or PrEP use over time, has been shown to be short, with most PrEP users stopping within 6-12 months. Furthermore, those most vulnerable to HIV often use PrEP for shorter periods. This qualitative study explores patient, provider, and contextual factors that influence PrEP persistence. In interviews with 25 PrEP users and 18 PrEP providers in San Francisco's safety net clinics, we analyze the perceived benefits and difficulties of taking PrEP, including structural barriers. We identify different steps in receipt of PrEP care (clinic visits and lab tests, pharmacy interactions, and medication adherence), and describe barriers and facilitators for providers and patients at each step. Our findings suggest that drop-in visits, streamlined testing, standing orders for labs, and 90-day PrEP prescriptions are highly desirable for many PrEP users. Also important are the proactive provision of adherence support and counseling, and referrals for housing, substance use, and mental health services.

High Interest in Doxycycline for Sexually Transmitted Infection Postexposure Prophylaxis in a Multicity Survey of Men Who Have Sex With Men Using a Social Networking Application.

Current strategies to prevent sexually transmitted infections (STIs) are not controlling the epidemic. The efficacy of doxycycline STI postexposure prophylaxis shows promise in pilot studies, but wider acceptability is unknown. A majority (84%) of diverse individuals using a gay social networking application were interested in doxycycline STI postexposure prophylaxis. Doxycycline STI postexposure prophylaxis should be examined in larger trials.

Social Network Factors as Correlates and Predictors of High Depressive Symptoms Among Black Men Who Have Sex with Men in HPTN 061.

Depression is linked to a range of poor HIV-related health outcomes. Minorities and men who have sex with men (MSM), suffer from high rates of depression. The current study examined the relationship between depressive symptoms and social network characteristics among community-recruited Black MSM in HPTN 061 from 6 US cities. A social network inventory was administer at baseline and depression was assessed with the CES-D at baseline, 6, and 12-months. At baseline, which included 1167 HIV negative and 348 HIV positive participants, size of emotional, financial, and medical support networks were significantly associated with fewer depressive symptoms. In longitudinal mixed models, size of emotional, financial, and medical support networks were significantly associated with fewer depressive symptoms as was the number of network members seen weekly. In the multivariate analyses, size of medical appointment network remained statistically significant (aOR 0.89, CI 0.81-0.98). These findings highlight the importance of network support of medical care on depression and suggest the value of support mobilization.

Sexually transmitted infections and pre-exposure prophylaxis: challenges and opportunities among men who have sex with men in the US.

Pre-Exposure Prophylaxis (PrEP) has shown high efficacy in preventing human immunodeficiency virus (HIV) infection among men who have sex with men (MSM) in several large clinical trials, and more recently in "real world" reports of clinical implementation and a PrEP demonstration project. Those studies also demonstrated high bacterial sexually transmitted infection (STI) incidence and raised the discussion of how PrEP may impact STI control efforts, especially in the setting of increasing Neisseria gonorrhoeae antimicrobial resistance and the increase in syphilis cases among MSM. Here, we discuss STIs as a driver of HIV transmission risk among MSM, and the potential opportunities and challenges for STI control afforded by expanded PrEP implementation among high-risk MSM.

Utilization of HIV prevention services across racial/ethnic groups among men who have sex with men in San Francisco, California, 2008.

Human Immunodeficiency Virus (HIV) infection in the US is disproportionally higher among Black and Latino men who have sex with men (MSM), compared to other racial/ethnic groups. The 2008 US National HIV Behavioral Surveillance (NHBS) survey of MSM was analyzed to compare utilization of HIV testing, receiving condoms, and individual and group HIV prevention programs among racial/ethnic groups in San Francisco, CA. Using a weighted analysis of the time-location sampling method, racial/ethnic subpopulation estimates were obtained for utilization of these services in the prior 12 months. There was no significant difference in utilization of HIV prevention services among Black (N=37), Latino (N=128), and White (N=275) MSM in San Francisco, CA. Overall 60-70 % of MSM reported their last HIV test within the past 12 months and more than 75 % reported receiving condoms in the last 12 months. However, less than 15 % of MSM reported utilizing individual or group HIV prevention counseling sessions. The NHBS survey demonstrate that the majority of MSM in San Francisco, CA have utilized one or more HIV prevention service in the past 12 months and that there were no racial/ethnic disparities in utilization of these services. However, the utilization of individual or group HIV prevention programs is low and HIV testing is below current recommendations for MSM.

Peer social support is associated with recent HIV testing among young black men who have sex with men.

Resiliency factors such as social support have been associated with more frequent HIV testing among MSM. We examined the association between social support and delayed HIV testing in the context of structural discrimination and individual factors among young Black MSM. We combined two independent cross-sectional samples recruited 1 year apart from a venue-based, modified time-location sampling study of young Black MSM aged 18-29 years in the US South. Our subsample (N = 813) was men who self-reported not being HIV positive and who indicated they had one or more male sex partners in the past 2 months. Using a social epidemiology framework we estimated associations of structural (racism and homophobia), social (social support from other Black MSM friends) and individual factors with delayed HIV testing (>6 months ago) using logistic regression. Bivariate analyses demonstrated that individual level variables as well as experiences of racism (OR 1.20, 95% CI 1.02-1.41) and homophobia (OR 1.49, 95 % CI 1.02-2.17) were associated with higher risk of delayed HIV testing. Receiving social support from other Black MSM friends was associated with lower risk of delayed HIV testing (OR 0.80, 95 % CI 0.67-0.95). In multivariable models, social support remained significantly associated with lower risk of delayed HIV testing after inclusion of structural and individual level variables. Social support has a positive and robust association with HIV testing among young Black MSM. Whether community building and development of resiliency factors can overcome structural, social, and individual-level barriers to HIV prevention and care for young Black MSM warrants further study.

Point-of-care urine tenofovir test predicts future HIV pre-exposure prophylaxis discontinuation among young users.

BACKGROUND: Young men who have sex with men and transgender women (YMSM/TGW) have disproportionately high HIV incidence and lower PrEP adherence. Point-of-care (POC) urine tenofovir (TFV) rapid assay (UTRA) testing permits real-time monitoring for nonadherence within clinical settings. We performed UTRA testing among PrEP users to examine the relationship between low PrEP adherence and future PrEP discontinuation, and the accuracy of POC testing compared to gold-standard liquid chromatography tandem mass spectrometry (LC/MS/MS). METHODS: YMSM/TGW participants (n = 100) were recruited during a daily PrEP visit. Logistic regression models analyzed the relationship between the primary predictor of urine POC assay results (cutoff 1,500 ng/mL) and the primary outcome of PrEP discontinuation, defined as no PrEP follow-up or prescription within 120 days. RESULTS: Overall, 19% of participants had low urine TFV and 21% discontinued PrEP, while 11% of participants self-reported low PrEP adherence (< 4 pills per week), which was only 43% sensitive/84% specific in predicting low TFV levels and was not associated with PrEP discontinuation. Low urine TFV level predicted PrEP discontinuation (AOR 6.1; 95% CI: 1.4-11; p = 0.005) and was 71% sensitive/90% specific for discontinuation after 120 days. Compared to LC/MS/MS, UTRA testing had a 98% positive and 100% negative predictive value. CONCLUSIONS: In a sample of YMSM/TGW on daily PrEP, POC UTRA testing predicted PrEP discontinuation more accurately than self-reported adherence, with high predictive values compared to LC/MS/MS. UTRA testing may be a clinical tool for directing preventive interventions towards those likelier to discontinue PrEP despite ongoing HIV vulnerability.

Polytopic fractional delivery of an HIV vaccine alters cellular responses and results in increased epitope breadth in a phase 1 randomized trial.

BACKGROUND: Elicitation of broad immune responses is understood to be required for an efficacious preventative HIV vaccine. This Phase 1 randomized controlled trial evaluated whether administration of vaccine antigens separated at multiple injection sites vs combined, fractional delivery at multiple sites affected T-cell breadth compared to standard, single site vaccination. METHODS: We randomized 90 participants to receive recombinant adenovirus 5 (rAd5) vector with HIV inserts gag, pol and env via three different strategies. The Standard group received vaccine at a single anatomic site (n = 30) compared to two polytopic (multisite) vaccination groups: Separated (n = 30), where antigens were separately administered to four anatomical sites, and Fractioned (n = 30), where fractions of each vaccine component were combined and administered at four sites. All groups received the same total dose of vaccine. FINDINGS: CD8 T-cell response rates and magnitudes were significantly higher in the Fractioned group than Standard for several antigen pools tested. CD4 T-cell response magnitudes to Pol were higher in the Separated than Standard group. T-cell epitope mapping demonstrated greatest breadth in the Fractioned group (median 8.0 vs 2.5 for Standard, Wilcoxon p = 0.03; not significant after multiplicity adjustment for co-primary endpoints). IgG binding antibody response rates to Env were higher in the Standard and Fractioned groups vs Separated group. INTERPRETATION: This study shows that the number of anatomic sites for which a vaccine is delivered and distribution of its antigenic components influences immune responses in humans. FUNDING: National Institute of Allergy and Infectious Diseases, NIH.

The effect of an HIV preexposure prophylaxis panel management strategy to increase preexposure prophylaxis prescriptions.

OBJECTIVE: The HIV preexposure prophylaxis optimization intervention (PrEP-OI) study evaluated the efficacy of a panel management intervention using PrEP coordinators and a web-based panel management tool to support healthcare providers in optimizing PrEP prescription and ongoing PrEP care. DESIGN: The PrEP-OI study was a stepped-wedge randomized clinical trial conducted across 10 San Francisco Department of Public Health primary care sites between November 2018 and September 2019. Each month, clinics one-by-one initiated PrEP-OI in random order until all sites received the intervention by the study team. METHODS: The primary outcome was the number of PrEP prescriptions per month. Secondary outcomes compared pre- and postintervention periods on whether PrEP was discussed and whether PrEP-related counseling (e.g., HIV risk assessment, risk reduction counseling, PrEP initiation/continuation assessment) was conducted. Prescription and clinical data were abstracted from the electronic health records. We calculated incidence rate ratios (IRR) and risk ratios (RR) to estimate the intervention effect on primary and secondary outcomes. RESULTS: The number of PrEP prescriptions across clinics increased from 1.85/month (standard deviation [SD] = 2.55) preintervention to 2.44/month (SD = 3.44) postintervention (IRR = 1.34; 95% confidence interval [CI] = 1.05-1.73; P  = 0.021). PrEP-related discussions during clinic visits (RR = 1.13; 95% CI = 1.04-1.22; P  = 0.004), HIV risk assessment (RR = 1.40; 95% CI = 1.14-1.72; P  = 0.001), and risk reduction counseling (RR = 1.16; 95% CI = 1.03-1.30; P  = 0.011) increased from the pre- to the postintervention period. Assessment of PrEP initiation/continuation increased over time during the postintervention period (RR = 1.05; 95% CI = 0.99-1.11; P  = 0.100). CONCLUSIONS: A panel management intervention using PrEP coordinators and a web-based panel management tool increased PrEP prescribing and improved PrEP-related counseling in safety-net primary care clinics.

Racial/ethnic and sexual behavior disparities in rates of sexually transmitted infections, San Francisco, 1999-2008.

BACKGROUND: Racial/ethnic minorities and men who have sex with men (MSM) represent populations with disparate sexually transmitted infection (STI) rates. While race-specific STI rates have been widely reported, STI rates among MSM is often challenging given the absence of MSM population estimates. We evaluated the race-specific rates of chlamydia and gonorrhea among MSM and non-MSM in San Francisco between 1999-2008. METHODS: 2000 US Census data for San Francisco was used to estimate the number of African-American, Asian/Pacific Islander, Hispanic, and white males. Data from National HIV Behavioral Surveillance (NHBS) MSM 1, conducted in 2004, was used to estimate the total number of MSM in San Francisco and the size of race/ethnic sub-populations of MSM. Non-MSM estimates were calculated by subtracting the number of estimated MSM from the total number of males residing in San Francisco. Rates of MSM and non-MSM gonorrhea and chlamydia reported between 1999 and 2008 were stratified by race/ethnicity. Ratios of MSM and non-MSM rates of morbidity were calculated by race/ethnicity. RESULTS: Between 1999-2008, MSM accounted for 72% of gonorrhea cases and 51% of chlamydia cases. Throughout the study period, African-American MSM had the highest chlamydia rate with 606 cases per 100,000 in 1999 increasing to 2067 cases per 100,000 in 2008. Asian/Pacific Islander MSM consistently had the lowest rate among MSM with 1003 cases per 100,000 in 2008. The ratio of MSM/non-MSM for chlamydia was highest among whites 11.6 (95% CI: 8.8-14.4) and Asian/Pacific Islanders 8.6 (95% CI: 6.2-11), and lowest among African-Americans 1.53 (95% CI: 1.2-1.9) and Hispanics 4.43 (95% CI: 2.8-6.0). Gonorrhea rates were similar for African-American, white, and Hispanic MSM between 2137-2441 cases per 100,000 in 2008. Asian/Pacific Islander MSM had the lowest gonorrhea rate with 865 cases per 100,000 in 2008. The ratio of MSM/non-MSM for gonorrhea was highest among whites 11.6 (95% CI: 8.8-14.4) and Asian/Pacific Islanders 8.6 (95% CI: 6.2-11), and lowest among African-Americans 1.53 (95% CI: 1.2-1.9) and Hispanics 4.43 (95% CI: 2.8-6.0). CONCLUSIONS: For all racial/ethnic groups in San Francisco, MSM carried a substantially higher burden of STIs compared to non-MSM except among African-American men. These racial and sexual behavior disparities warrant further public health attention and resources.

Missed opportunities to prevent HIV infections among pre-exposure prophylaxis users: a population-based mixed methods study, San Francisco, United States.

INTRODUCTION: Pre-exposure prophylaxis (PrEP) is highly effective, although PrEP adherence and persistence has been variable during real world implementation. Little is known about missed opportunities to enhance PrEP adherence among individuals who later HIV seroconverted after using PrEP. The goal of this analysis was to identify all HIV infections among individuals who had accessed PrEP in an integrated health system in San Francisco, and to identify potentially intervenable factors that could have prevented HIV infection through in-depth interviews with people who HIV seroconverted after using PrEP. METHODS: We identified individuals who initiated PrEP in an integrated safety-net public health system and performed in-depth chart review to determine person-time on and after stopping PrEP over six years. We identified all PrEP seroconversions using the Centers for Disease Control and Prevention's Enhanced HIV/AIDS Reporting System and then calculated HIV incidence while using PrEP and during gaps in use. We then performed in-depth interviews with those who seroconverted. RESULTS: Overall, 986 initiated PrEP across the San Francisco Department of Public Health from July 2012 to November 2018. Data were gathered from 895 person-years on PrEP and 953 after stopping PrEP. The HIV incidence was 7.5-fold higher after stopping PrEP compared to while on PrEP (95% CI 1 to 336). Of the eight individuals who HIV seroconverted; only one was taking PrEP at the time of seroconversion but was using on-demand PrEP inconsistently. All eight agreed to qualitative interviews. Major barriers to PrEP persistence included substance use, mental health and housing loss; difficulty accessing PrEP due to cost, insurance, and the cost and time of medical visits; difficulty weighing PrEP's benefit versus self-perceived risk; and entering a primary partnership. The individual who developed HIV using on-demand PrEP reported confusion about the dosing regimen and which sexual encounters required accompanying PrEP dosing. CONCLUSIONS: HIV incidence during gaps in PrEP use was nearly eight-fold higher than while on PrEP in this large cohort in San Francisco. Many individuals who stop PrEP remain at risk of HIV, and participants reported that proactive outreach could potentially have prevented HIV infections. Individuals using non-daily PrEP may require additional education and support in the United States.

Racial/ethnic and HIV risk category disparities in preexposure prophylaxis discontinuation among patients in publicly funded primary care clinics.

OBJECTIVE: Dissemination of preexposure prophylaxis (PrEP) is a priority for reducing new HIV infections, especially among vulnerable populations. However, there are limited data available on PrEP discontinuation following initiation, an important component of the PrEP cascade. DESIGN: Patients receiving PrEP within the San Francisco Department of Public Health Primary Care Clinics (SFPCC) are included in a PrEP registry if they received a PrEP prescription, were not receiving postexposure prophylaxis, and not known to be HIV-positive. METHODS: We calculated PrEP discontinuation for patients initiating PrEP at any time from January 2012 to July 2017 and evaluated their association with demographic and risk variables using Cox regression analysis. RESULTS: Overall, 348 patients received PrEP over the evaluation period. The majority (84%) were men, and the cohort was racially/ethnically diverse. The median duration of PrEP use was 8.3 months. In adjusted analysis, PrEP discontinuation was lower among older patients (aHR 0.89; 95% CI 0.80-0.99; P = 0.03); but higher among black patients (compared with white patients; aHR 1.87; 95% CI 1.27-2.74; P = 0.001), patients who inject drugs (aHR 4.80; 95% CI 2.66-8.67; P < 0.001), and transgender women who have sex with men (compared with MSM; aHR 1.94; 95% CI 1.36-2.77; P < 0.001). CONCLUSION: Age, racial/ethnic, and risk category disparities in PrEP discontinuation were identified among patients in a public health-funded primary care setting. Further efforts are needed to understand and address PrEP discontinuation among priority populations to maximize the preventive impact of PrEP, and reverse HIV-related disparities at a population level.

Missed Visits Associated With Future Preexposure Prophylaxis (PrEP) Discontinuation Among PrEP Users in a Municipal Primary Care Health Network.

BACKGROUND: Maintaining retention in preexposure prophylaxis (PrEP) care among diverse patient populations will be needed to support PrEP's efficacy. We characterized patterns of PrEP care retention in a US municipal primary care health network and examined whether missed visits, a metric of care retention that is easy to evaluate in clinic, are associated with subsequent discontinuation. METHODS: We included individuals on PrEP from July 2012 until August 2017 in the San Francisco Primary Care Clinics, a 15-clinic municipal health network. We categorized PrEP usage patterns as follows: early discontinuation (<90 days), later discontinuation (after ≥90 days), and continuing use at the end of follow-up. We first examined early discontinuation using adjusted Poisson regression. In patients who continued PrEP for ≥90 days, we examined factors associated with late discontinuation. RESULTS: Of the 364 individuals who started PrEP, 16% discontinued PrEP before 90 days, 46% discontinued later, and 38% were retained in care over a median 12 months of observation. Transgender women were more likely to discontinue PrEP early (adjusted risk ratio; 2.16; 95% confidence interval, 1.36-3.49), and younger users were more likely to discontinue late (0.82 per 10-year increase in age; .70-.96), as were persons who use illicit drugs (1.59; 1.02-2.47). Missed visits during use of PrEP were associated with future discontinuation (adjusted risk ratio, 1.52; 95% confidence interval, 1.14-2.03). Later year of current PrEP use was associated with both early and late discontinuation. CONCLUSION: Diverse populations may require differentiated care to continue PrEP. Missed visits should trigger tailored interventions to maximize the impact of PrEP.

Provider Adherence to Pre-exposure Prophylaxis Monitoring Guidelines in a Large Primary Care Network.

Insufficient pre-exposure prophylaxis (PrEP) laboratory monitoring could increase HIV resistance and sexually transmitted infections. We examined test-ordering in a primary care network. Providers did not order HIV testing before almost one-quarter of PrEP initiations; panel management was associated with higher testing. Effective monitoring is needed to maximize PrEP's preventive impact.

Brief Report: A Panel Management and Patient Navigation Intervention Is Associated With Earlier PrEP Initiation in a Safety-Net Primary Care Health System.

BACKGROUND: Timely pre-exposure prophylaxis (PrEP) initiation is critical in at-risk populations, given that HIV acquisition risk persists during delays. Time to treatment initiation, a key metric in HIV care, has not been explored among PrEP users. Interventions that reduce time to PrEP initiation could prevent HIV infections. SETTING: Individuals initiating PrEP in a large primary care health network of 15 clinics, the San Francisco Primary Care Clinics (SFPCC), from July 2012 to July 2017 (N = 411). METHODS: We examined factors associated with time from first PrEP discussion with a provider to PrEP initiation date using an adjusted Cox proportional-hazards model, with hazard ratios (HRs) >1 indicating earlier initiation. We also examined the relationship between delayed PrEP initiation and PrEP persistence (staying on PrEP) in an adjusted Cox proportional-hazards model. RESULTS: PrEP users initiated PrEP after a median of only 7 days. However, there were notable outliers, with 29% waiting >30 days and 12% waiting >90 days. In an adjusted proportional-hazards model, a panel management and patient navigation intervention was associated with earlier PrEP initiation [HR: 1.5; 95% confidence interval (CI): 1.1 to 2.0], whereas only other race/ethnicity compared with white race was associated with delayed PrEP initiation (HR: 0.7; 95% CI: 0.5 to 1.0). Delayed PrEP initiation >30 days was associated with shorter PrEP persistence in an adjusted proportional-hazards model (HR: 1.3; 95% CI: 1.0 to 1.7). CONCLUSIONS: PrEP initiation within a week is feasible in a primary care safety-net health system. Setting a goal of rapid PrEP initiation, with the support of panel management and patient navigation, could address delays in at-risk groups.

Distribution of Behavioral Patterns Before Infection Among San Francisco Men Who Have Sex With Men Newly Infected With HIV in 2014.

BACKGROUND: Despite continued reductions in the number of HIV cases reported among San Francisco men who have sex with men (MSM) and the HIV-prevention potential offered by pharmaceutical tools such as pre-exposure prophylaxis (PrEP), there are uncertainties, particularly given reported decreases in consistent condom use. A key uncertainty is what groups of MSM should be targeted. This study estimates the distribution of behavioral patterns before infection among San Francisco MSM newly infected with HIV in 2014. METHODS: We used a novel modeling approach. The approach uses estimates from the National HIV Behavioral Surveillance System for MSM, the Medical Monitoring Project, 2 trials of PrEP, and a meta-analysis of per-act risks of HIV infection. RESULTS: The modeling study suggests that 76% of newly HIV-infected MSM in 2014 were individuals with no discernible strategy in the 6 months before infection: that is, they had condomless receptive anal intercourse with one or more partners not perceived to be HIV uninfected. An estimated 7% of newly infected MSM were serosorters before infection. CONCLUSIONS: Prevention efforts in San Francisco must reach HIV-uninfected MSM with no discernible behavioral strategy, a group that constitutes 8% of HIV-uninfected MSM in the city. Our study suggests that if all HIV-uninfected, San Francisco MSM with no discernible strategy had been on PrEP in 2014, there would have been 70% fewer HIV infections among San Francisco MSM. Uncertainty analysis suggests that PrEP's impact may be maximized by encouraging PrEP persistence and concomitant reductions in sexual risk behaviors.