Sexually Transmitted Infections Among Men and Transgender Women Using HIV Pre-exposure Prophylaxis in a Large Integrated Health System-A Cohort Study.

BACKGROUND: Sexually transmitted infections (STIs) are common in people using pre-exposure prophylaxis (PrEP). We examined risk and factors associated with STIs in a cohort of PrEP users in an integrated health system in the United States. SETTING: The Kaiser Permanente Southern California is a large integrated health system that provides comprehensive medical services to approximately 4.7 million demographically diverse members. METHODS: We identified men and transgender women initiating PrEP between January 1, 2014, and June 1, 2018, and followed through December 31, 2018. Demographic and clinical factors potentially associated with the risk of bacterial STIs during PrEP use were evaluated using Poisson regression models. RESULTS: Among 5042 individuals tested for STIs with 7198 person-years of follow-up, 1709 (33.9%) had at least one new STI. The estimated incidence of STIs was 48.3 per 100 person-years, and the most common STI was rectal chlamydia. Most repeat STIs (61.4%) occurred <180 days apart. In a multivariable analysis, an history of STIs in the prior 6 months through 7 days after the PrEP initiation was the most prominent risk factor of STIs during PrEP use (adjusted risk ratio: 1.78, 95% confidence intervals: 1.65 to 1.93). Other risk factors included younger age (<35 years), being Hispanic, and having a history of alcohol use disorder or drug use disorder. CONCLUSIONS: Quarterly STI testing and targeted intervention to mitigate STI risk are warranted for young and racial minority PrEP users, particularly for those with prior history of STIs and substance use disorders.

Referral Linkage to Preexposure Prophylaxis Care and Persistence on Preexposure Prophylaxis in an Integrated Health Care System.

BACKGROUND: Successful linkage to preexposure prophylaxis (PrEP) and retention in care are important for HIV prevention. We examined gaps in PrEP care following referral and factors associated with PrEP linkage and persistence in an integrated health care system in the United States. METHODS: We identified individuals referred for PrEP from 2014 to 2017 at the Kaiser Permanente Southern California using electronic health records and assessed linkage to care, PrEP prescription orders and fills, and PrEP persistence (medication possession ratio ≥80%) in the year after the first fill. We evaluated demographic and clinical factors potentially associated with PrEP linkage and persistence using a series of multivariable modified Poisson regression models. RESULTS: Of 2995 referred individuals, 74.9% were linked to PrEP care. Nearly all those linked to care were prescribed PrEP and filled a prescription, but only 47.4% of those who filled a prescription were persistent on PrEP. Individuals aged <25 years (vs ≥25 years), female subjects (vs males), and individuals with high-deductible insurance (vs no high deductible) were less likely to be linked to care. Individuals aged <25 years and Hispanics (vs non-Hispanic whites) were less likely to be persistent. Those with alcohol use disorder were more likely to be linked to PrEP care but less likely to be persistent. New HIV diagnoses occurred in 38 individuals, and only 1 had PrEP in possession at diagnosis. CONCLUSIONS: We observed PrEP care gaps and disparities among individuals referred for PrEP. Patient-centered interventions are needed in primary care to address barriers to successful PrEP linkage and persistence.

Characterization of drug-resistant influenza A(H7N9) variants isolated from an oseltamivir-treated patient in Taiwan.

BACKGROUND: Patients contracting influenza A(H7N9) infection often developed severe disease causing respiratory failure. Neuraminidase (NA) inhibitors (NAIs) are the primary option for treatment, but information on drug-resistance markers for influenza A(H7N9) is limited. METHODS: Four NA variants of A/Taiwan/1/2013(H7N9) virus containing a single substitution (NA-E119V, NA-I222K, NA-I222R, or NA-R292K) recovered from an oseltamivir-treated patient were tested for NAI susceptibility in vitro; their replicative fitness was evaluated in cell culture, mice, and ferrets. RESULTS: NA-R292K led to highly reduced inhibition by oseltamivir and peramivir, while NA-E119V, NA-I222K, and NA-I222R caused reduced inhibition by oseltamivir. Mice infected with any virus showed severe clinical signs with high mortality rates. NA-I222K virus was the most virulent in mice, whereas virus lacking NA change (NA-WT) and NA-R292K virus seemed the least virulent. Sequence analysis suggests that PB2-S714N increased virulence of NA-I222K virus in mice; NS1-K126R, alone or in combination with PB2-V227M, produced contrasting effects in NA-WT and NA-R292K viruses. In ferrets, all viruses replicated to high titers in the upper respiratory tract but produced only mild illness. NA-R292K virus, showed reduced replicative fitness in this animal model. CONCLUSIONS: Our data highlight challenges in assessment of the replicative fitness of H7N9 NA variants that emerged in NAI-treated patients.