Using Electronic Health Records to Improve HIV Preexposure Prophylaxis Care: A Randomized Trial.

BACKGROUND: Preexposure prophylaxis (PrEP) use remains limited and inequitable, and strategies are needed to improve PrEP provision in primary care. METHODS: We conducted a cluster randomized trial at Kaiser Permanente, San Francisco, to evaluate the effectiveness of a clinical decision support intervention guided by an electronic health record (EHR)-based HIV risk prediction model to improve PrEP provision. Primary care providers (PCPs) were randomized to usual care or intervention, with PCPs who provide care to people with HIV balanced between arms. PCPs in the intervention arm received an EHR-based staff message with prompts to discuss HIV prevention and PrEP before upcoming in-person or video visits with patients whose predicted 3-year HIV risk was above a prespecified threshold. The main study outcome was initiation of PrEP care within 90 days, defined as PrEP discussions, referrals, or prescription fills. RESULTS: One hundred twenty-one PCPs had 5051 appointments with eligible patients (2580 usual care; 2471 intervention). There was a nonsignificant increase in initiation of PrEP care in the intervention arm (6.0% vs 4.5%, HR 1.32, 95% CI: 0.84 to 2.1). There was a significant interaction by HIV provider status, with an intervention HR of 2.59 (95% CI: 1.30 to 5.16) for HIV providers and 0.89 (95% CI: 0.59 to 1.35) for non-HIV providers (P-interaction <0.001). CONCLUSION: An EHR-based intervention guided by an HIV risk prediction model substantially increased initiation of PrEP care among patients of PCPs who also care for people with HIV. Higher-intensity interventions may be needed to improve PrEP provision among PCPs less familiar with PrEP and HIV care.

Characterization of HIV Preexposure Prophylaxis Use Behaviors and HIV Incidence Among US Adults in an Integrated Health Care System.

Importance: Long-term follow-up is needed to evaluate gaps in HIV preexposure prophylaxis (PrEP) care delivery and to identify individuals at risk for falling out of care. Objective: To characterize the PrEP continuum of care, including prescription, initiation, discontinuation, and reinitiation, and evaluate incident HIV infections. Design, Setting, and Participants: This retrospective cohort study used data from the electronic health records (EHR) at Kaiser Permanente Northern California to identify individuals aged 18 years and older who received PrEP care between July 2012 and March 2019. Individuals were followed up from date of linkage (defined as a PrEP referral or PrEP-coded encounter) until March 2019, HIV diagnosis, discontinuation of health plan membership, or death. Data were analyzed from December 2019 to January 2021. Exposures: Sociodemographic factors included age, sex, race and ethnicity, and neighborhood deprivation index, and clinical characteristics were extracted from the EHR. Main Outcomes and Measures: The primary outcomes were attrition at each step of the PrEP continuum of care and incident HIV infections. Results: Among 13 906 individuals linked to PrEP care, the median (interquartile range [IQR]) age was 33 (27-43) years, 6771 individuals (48.7%) were White, and 13 227 (95.1%) were men. Total follow-up was 26 210 person-years (median [IQR], 1.6 [0.7-2.8] years). Of individuals linked to PrEP care, 88.1% (95% CI, 86.1%-89.9%) were prescribed PrEP and of these, 98.2% (95% CI, 97.2%-98.8%) initiated PrEP. After PrEP initiation, 52.2% (95% CI, 48.9%-55.7%) discontinued PrEP at least once during the study period, and 60.2% (95% CI, 52.2%-68.3%) of these individuals subsequently reinitiated. Compared with individuals aged 18 to 25 years, older individuals were more likely to receive a PrEP prescription (eg, age >45 years: hazard ratio [HR], 1.21 [95% CI, 1.14-1.29]) and initiate PrEP (eg, age >45 years: HR, 1.09 [95% CI, 1.02-1.16]) and less likely to discontinue (eg, age >45 years: HR, 0.46 [95% CI, 0.42-0.52]). Compared with White patients, African American and Latinx individuals were less likely to receive a PrEP prescription (African American: HR, 0.74 [95% CI, 0.69-0.81]; Latinx: HR, 0.88 [95% CI, 0.84-0.93]) and initiate PrEP (African American: HR, 0.87 [95% CI, 0.80-0.95]; Latinx: HR, 0.90 [95% CI, 0.86-0.95]) and more likely to discontinue (African American: HR, 1.36 [95% CI, 1.17-1.57]; Latinx: 1.33 [95% CI, 1.22-1.46]). Similarly, women, individuals with lower neighborhood-level socioeconomic status (SES), and persons with a substance use disorder (SUD) were less likely to be prescribed (women: HR, 0.56 [95% CI, 0.50-0.62]; lowest SES: HR, 0.72 [95% CI, 0.68-0.76]; SUD: HR, 0.88 [95% CI, 0.82-0.94]) and initiate PrEP (women: HR, 0.71 [95% CI, 0.64-0.80]; lower SES: HR, 0.93 [95% CI, 0.87-.0.99]; SUD: HR, 0.88 [95% CI, 0.81-0.95]) and more likely to discontinue (women: HR, 1.99 [95% CI, 1.67-2.38]); lower SES: HR, 1.40 [95% CI, 1.26-1.57]; SUD: HR, 1.23 [95% CI, 1.09-1.39]). HIV incidence was highest among individuals who discontinued PrEP and did not reinitiate PrEP (1.28 [95% CI, 0.93-1.76] infections per 100 person-years). Conclusions and Relevance: These findings suggest that gaps in the PrEP care continuum were concentrated in populations disproportionately impacted by HIV, including African American individuals, Latinx individuals, young adults (aged 18-25 years), and individuals with SUD. Comprehensive strategies to improve PrEP continuum outcomes are needed to maximize PrEP impact and equity.

Early Adopters of Event-driven Human Immunodeficiency Virus Pre-exposure Prophylaxis in a Large Healthcare System in San Francisco.

Among 279 patients within a large healthcare system in San Francisco, event-driven HIV pre-exposure prophylaxis using a 2-1-1 regimen was a desirable alternative to daily dosing. Problems with adherence, planning sex in advance, or side effects were infrequent (13.9%). We found no new HIV infections over 136 person-years of follow-up.

Alcohol and drug use, partner PrEP use and STI prevalence among people with HIV.

OBJECTIVES: People with HIV (PWH) have a high burden of bacterial sexually transmitted infections (STIs). We examined the relationship of alcohol and drug use and partner pre-exposure prophylaxis (PrEP) use to STI prevalence in a cohort of PWH with a history of unhealthy alcohol use. METHODS: We analysed data from a primary care-based alcohol intervention study at Kaiser Permanente Northern California (KPNC). Participants were recruited between April 2013 and May 2015 and were followed for up to 24 months. We linked participant responses to questions from the 24 month follow-up interview, including alcohol and drug use and partner PrEP use, with STI test results (ie, syphilis, chlamydia, gonorrhoea) in the KPNC electronic health record. Prevalence ratios (PR) were estimated using Poisson models fitted with robust variance estimators to evaluate the association of substance use and partner use of PrEP with STIs. RESULTS: In the analytic sample (n=465), the median age was 52 years (IQR 45-59); 67% were white; 95% were men who have sex with men. Thirty-two per cent of participants had HIV-positive partners only; 31% had HIV-negative partners with at least one on PrEP in the previous year and 37% had HIV-negative partners without any on PrEP. Twenty-three per cent reported alcohol and drug use prior to sex in the last 6 months. Eight per cent of participants had an STI. Partner PrEP use (adjusted PR (aPR) 2.99 (95% CI 1.11 to 8.08)) was independently associated with higher STI prevalence. Participants who reported use of alcohol (aPR 1.53 (0.61 to 3.83)), drugs (aPR 1.97 (0.71 to 5.51)) or both (aPR 1.93 (0.75 to 4.97)) prior to sex had a higher STI prevalence. CONCLUSIONS: The higher prevalence of STIs among PWH with unhealthy alcohol use who have partners on PrEP suggests that this subgroup may be a high-yield focus for targeted outreach, STI screening and sexual health counselling.

Use of electronic health record data and machine learning to identify candidates for HIV pre-exposure prophylaxis: a modelling study.

BACKGROUND: The limitations of existing HIV risk prediction tools are a barrier to implementation of pre-exposure prophylaxis (PrEP). We developed and validated an HIV prediction model to identify potential PrEP candidates in a large health-care system. METHODS: Our study population was HIV-uninfected adult members of Kaiser Permanente Northern California, a large integrated health-care system, who were not yet using PrEP and had at least 2 years of previous health plan enrolment with at least one outpatient visit from Jan 1, 2007, to Dec 31, 2017. Using 81 electronic health record (EHR) variables, we applied least absolute shrinkage and selection operator (LASSO) regression to predict incident HIV diagnosis within 3 years on a subset of patients who entered the cohort in 2007-14 (development dataset), assessing ten-fold cross-validated area under the receiver operating characteristic curve (AUC) and 95% CIs. We compared the full model to simpler models including only men who have sex with men (MSM) status and sexually transmitted infection (STI) positivity, testing, and treatment. Models were validated prospectively with data from an independent set of patients who entered the cohort in 2015-17. We computed predicted probabilities of incident HIV diagnosis within 3 years (risk scores), categorised as low risk (<0·05%), moderate risk (0·05% to <0·20%), high risk (0·20% to <1·0%), and very high risk (≥1·0%), for all patients in the validation dataset. FINDINGS: Of 3 750 664 patients in 2007-17 (3 143 963 in the development dataset and 606 701 in the validation dataset), there were 784 incident HIV cases within 3 years of baseline. The LASSO procedure retained 44 predictors in the full model, with an AUC of 0·86 (95% CI 0·85-0·87) for incident HIV cases in 2007-14. Model performance remained high in the validation dataset (AUC 0·84, 0·80-0·89). The full model outperformed simpler models including only MSM status and STI positivity. For the full model, flagging 13 463 (2·2%) patients with high or very high HIV risk scores in the validation dataset identified 32 (38·6%) of the 83 incident HIV cases, including 32 (46·4%) of 69 male cases and none of the 14 female cases. The full model had equivalent sensitivity by race whereas simpler models identified fewer black than white HIV cases. INTERPRETATION: Prediction models using EHR data can identify patients at high risk of HIV acquisition who could benefit from PrEP. Future studies should optimise EHR-based HIV risk prediction tools and evaluate their effect on prescription of PrEP. FUNDING: Kaiser Permanente Community Benefit Research Program and the US National Institutes of Health.

Low-Intensity Outreach to Increase Uptake of HIV Preexposure Prophylaxis Among Patients with Sexually Transmitted Infections.

We piloted a low-intensity outreach intervention to increase linkage to PrEP care among HIV-uninfected individuals with rectal sexually transmitted infections or syphilis. We sent a secure email message or letter with information about accessing PrEP. Of those sent an email, 12.4% were linked to PrEP care; linkage differed by race/ethnicity, ranging from 0% of Black individuals to 32% of Hispanic individuals (P = 0.019). No individuals sent letters were linked to PrEP care. A one-time secure email to high-risk patients is feasible to increase linkage to PrEP care. Studies are needed to evaluate scalable interventions to increase PrEP uptake in at-risk populations.

Barriers to preexposure prophylaxis use among individuals with recently acquired HIV infection in Northern California.

Barriers to HIV preexposure prophylaxis (PrEP) use have not been well-characterized in people who became HIV-infected, all of whom could have benefited from PrEP. We invited Kaiser Permanente Northern California members diagnosed with HIV during 2014-2016, following a negative HIV test in the prior year, to complete a survey assessing barriers to PrEP use before HIV diagnosis. Of 268 patients surveyed, 122 (46%) responded. Median age was 36, most (84%) were men who have sex with men, and 64% were of minority racial/ethnic background. Thirty-six (30%) had discussed PrEP with a provider, of whom 10 were diagnosed with HIV at PrEP intake. Overall, only 5 (4.1%) had used PrEP, and all 5 discontinued before diagnosis. Among all respondents, the most common barrier to PrEP use was lack of PrEP awareness (51%). Among those aware of PrEP, the most common barriers were cost/insurance concerns (36%) and perceived low risk for HIV (24%). Lack of PrEP awareness ranged from 39% among those aged 25-34 to 88% among those aged <25 (P = 0.011), and from 33% among Hispanics to 69% among Blacks (P = 0.055). Increasing awareness and affordability of PrEP, and facilitating accurate assessment of HIV risk, are critical to reducing missed opportunities for PrEP.

HIV Infection and Drug Resistance with Unsupervised Use of HIV Pre-Exposure Prophylaxis.

Although the Centers for Disease Control and Prevention currently only recommend daily dosing of HIV pre-exposure prophylaxis (PrEP), an on-demand PrEP dosing strategy that includes doses before and after sexual activity has been shown to reduce risk for HIV acquisition in men who have sex with men. In this letter, we report a case of HIV infection and drug resistance in a patient using PrEP outside of regular clinical care, adopting a sporadic, suboptimal dosing strategy with pills he obtained from his sexual partners. This case illustrates the potential risks of PrEP use without provider monitoring to ensure safe and effective dosing and laboratory follow-up, as well as key challenges that must be addressed as nondaily PrEP use becomes more common outside of controlled research settings.

Risk Perception, Sexual Behaviors, and PrEP Adherence Among Substance-Using Men Who Have Sex with Men: a Qualitative Study.

The antiretroviral drug combination emtricitabine and tenofovir disoproxil fumarate (TDF/FTC) taken as pre-exposure prophylaxis (PrEP) is effective in preventing HIV infection, yet it also requires adherence and potentially decreases condom use. This study sought to examine these issues among a key population at risk of HIV infection, substance-using men who have sex with men (MSM). We conducted semi-structured interviews with an ethnically diverse sample of 30 young (aged 20-35) MSM prescribed PrEP within a large integrated healthcare system in San Francisco, who had reported recent drug use or hazardous drinking and one or more missed doses of PrEP. We explored participants' risk perception and sexual risk behavior, drug and alcohol use, and PrEP adherence in the context of substance use. Interviews were transcribed and coded using a directed content analysis approach to identify key categories and commonalities, and differences across participants. Salient subcategories included positive psychological effects of being on PrEP (e.g., decreased anxiety, feelings of empowerment), social effects (e.g., reduced HIV stigma), and reduction in overall perceptions of HIV risk. While overall reported use of condoms went down and many reported a brief period of increased condomless sex following PrEP initiation, others continued condom use with most of their sexual partners. Contextual factors influencing their decision to engage in condomless sex included how well they knew the partner and whether the partner was on PrEP or HIV antiretroviral treatment. Factors associated with poor adherence included disruptions in daily routine and use of alcohol and methamphetamine. PrEP-prescribing clinicians should support their patients in making informed decisions about condom use and identifying strategies to maximize adherence in the context of substance use.

Preexposure Prophylaxis for HIV Prevention in a Large Integrated Health Care System: Adherence, Renal Safety, and Discontinuation.

BACKGROUND: Placebo-controlled and open-label studies have demonstrated the safety and efficacy of daily oral preexposure prophylaxis (PrEP) in preventing HIV infection, but data are limited on real-world PrEP use. METHODS: We conducted a cohort study from July 2012 through June 2015 of Kaiser Permanente Northern California members initiating PrEP. We assessed pharmacy refill adherence and discontinuation, decreases in estimated glomerular filtration rate (eGFR), and sexually transmitted infection (STI)/HIV incidence. RESULTS: Overall, 972 individuals initiated PrEP, accumulating 850 person-years of PrEP use. Mean adherence was 92% overall. Black race/ethnicity [adjusted risk ratio (aRR) 3.0; 95% confidence interval: 1.7 to 5.1, P < 0.001], higher copayments (aRR 2.0; 1.2 to 3.3, P = 0.005), and smoking (aRR 1.6; 1.1 to 2.3, P = 0.025) were associated with <80% adherence. PrEP was discontinued by 219 (22.5%); female sex (aRR 2.6; 1.5 to 4.6, P < 0.001) and drug/alcohol abuse (aRR 1.8; 1.3 to 2.6, P = 0.002) were associated with discontinuation. Among 909 with follow-up creatinine testing, 141 (15.5%) had an eGFR <70 mL·min·1.73 m and 5 (0.6%) stopped PrEP because of low eGFR. Quarterly STI positivity was high and increased over time for rectal chlamydia (P < 0.001) and urethral gonorrhea (P = 0.012). No HIV seroconversions occurred during PrEP use; however, 2 occurred in individuals who discontinued PrEP after losing insurance coverage. CONCLUSIONS: PrEP adherence was high in clinical practice, consistent with the lack of HIV seroconversions during PrEP use. Discontinuation because of renal toxicity was rare. STI screening every 6 months, as recommended by current guidelines, may be inadequate. Strategies are needed to increase PrEP access during gaps in insurance coverage.

Successful Implementation of HIV Preexposure Prophylaxis: Lessons Learned From Three Clinical Settings.

The past 3 years have marked a transition from research establishing the safety and efficacy of HIV preexposure prophylaxis (PrEP) to questions about how to optimize its implementation. Until recently, PrEP was primarily offered as part of randomized controlled trials or open-label studies. These studies highlighted the key components of PrEP delivery, including regular testing for HIV and other sexually transmitted infections (STIs), adherence and risk-reduction support, and monitoring for renal toxicity. PrEP is now increasingly provided in routine clinical settings. This review summarizes models for PrEP implementation from screening through initiation and follow-up, focusing on the strengths and weaknesses of three delivery systems: a health maintenance organization, an STI clinic, and a primary care practice. These early implementation experiences demonstrate that PrEP can be successfully delivered across a variety of settings and highlight strategies to streamline PrEP delivery in clinical practice.

Acceptability and feasibility of HIV self-testing among men who have sex with men in Peru and Brazil.

HIV self-testing has the potential to increase testing frequency and uptake. This pilot study assessed the feasibility and acceptability of HIV self-testing in a sample of sexually active men who have sex with men (MSM) in Peru and Brazil. Participants were trained to use a whole blood rapid HIV self-test and instructed to use the self-test monthly during this three-month study. Test acceptability was measured with self-reported use of the test at the one-month and three-month study visits, and test feasibility was assessed by direct observation of self-test administration at the final three-month visit. A total of 103 participants (52 in Peru and 51 in Brazil) were enrolled, and 86% completed the three-month study. Nearly all participants reported use of the self-test (97% at one-month and 98% at three-month visit), and all participants correctly interpreted the self-administered test results when observed using the test at the final study visit. HIV self-testing with a blood-based assay was highly acceptable and feasible. HIV self-testing may have the potential to increase testing frequency and to reach high-risk MSM not currently accessing HIV-testing services.

No New HIV Infections With Increasing Use of HIV Preexposure Prophylaxis in a Clinical Practice Setting.

Referrals for and initiation of preexposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection increased dramatically in a large clinical practice setting since 2012. Despite high rates of sexually transmitted infections among PrEP users and reported decreases in condom use in a subset, there were no new HIV infections in this population.

Antiretroviral drug resistance among antiretroviral-naïve and treatment experienced patients infected with HIV in Iran.

Resistance to antiretroviral therapy (ART) threatens the success of programs to reduce HIV morbidity and mortality, particularly in countries with few treatment options. In the present study, genotype and phenotype data from ART-naïve and experienced hospitalized patients infected with HIV in Tehran, Iran were used to assess the prevalence and types of transmitted (TDR) and acquired drug resistance (ADR) mutations. All 30 participants naïve to ART and 62 of 70 (88.6%) participants receiving ART had detectable viral loads. Among participants receiving ART with sequencing data available (n = 62), 36 (58.1%) had at least one drug resistance mutation; the most common mutations were K103N (21.0%), M184V (19.4%), and the thymidine analogue mutations. Seven (11.3%), 27 (43.5%), and two (3.2%) of these participants had resistance to one, two, and three drug classes, respectively. High-level resistance to efavirenz (EFV) was more common among participants on EFV-based regimens than high-level lopinavir/ritonivar (LPV/r) resistance among those on LPV/r-based regimens (55.3% vs. 6.7%, P < 0.0001). Two (6.7%) antiretroviral-naïve participants had K103N mutations. These findings document an alarmingly high frequency of multiple HIV drug class resistance in Iran, confirm the presence of TDR, and highlight the need for systematic viral load monitoring and drug resistance testing, including at diagnosis. Expanded access to new antiretroviral medications from additional drug classes is needed.

HCV, HBV, and HIV seroprevalence, coinfections, and related behaviors among male injection drug users in Arak, Iran.

This study explored the prevalence and related risk behaviors for hepatitis C (HCV), hepatitis B (HBV), and human immunodeficiency virus (HIV) among a sample of male injection drug users (IDUs) in Arak, Iran. One hundred male IDUs attending methadone maintenance clinics between April and September 2012 were enrolled and evaluated for HCV, HBV, and HIV infection. The majority of study participants (56%) had evidence of HCV exposure, 6% had evidence of HBV, and 19% were HIV-infected. Coinfections were frequent; 15% had evidence of HIV and HCV, 6% had evidence of HBV and HCV, and 5% had serologic markers for all three infections. Most (84%) were susceptible to HBV infection. A history of any syringe sharing (54%) and syringe sharing in prison (25%) were common. In bivariate analyses, a history of any syringe sharing and syringe sharing in prison were both associated with all three viral infections. The high prevalence of HCV, HBV, HIV, and coinfections among IDU in Arak is concerning and indicates rapid disease spread outside of Iran's main urban centers. Prevention efforts should expand vaccination for IDUs who are nonimmune to HBV and continue to target syringe sharing with efforts such as needle exchange programs, including inside prisons.