Improved Gonorrhea and Chlamydia Testing Among Men Who Have Sex With Men Living With HIV Through Implementation of Self-Collected Tests.

ABSTRACT: We implemented self-collected gonorrhea/chlamydia testing in 17 medical centers in California serving men who have sex with men living with HIV. From 2012 to 2018, gonorrhea/chlamydia testing increased from 45.2% to 63.4%. Among those tested, rectal testing increased from 42.0% to 77.3%; pharyngeal testing increased from 31.0% to 79.9% (all, Ptrend < 0.0001).

Health System-Based Unhealthy Alcohol Use Screening and Treatment Comparing Demographically Matched Participants With and Without HIV.

BACKGROUND: Unhealthy alcohol use among persons living with HIV (PLWH) is linked to significant morbidity, and use of alcohol services may differ by HIV status. Our objective was to compare unhealthy alcohol use screening and treatment by HIV status in primary care. METHODS: Cohort study of adult (≥18 years) PLWH and HIV-uninfected participants frequency matched 20:1 to PLWH by age, sex, and race/ethnicity who were enrolled in a large integrated healthcare system in the United States, with information ascertained from an electronic health record. Outcomes included unhealthy alcohol screening, prevalence, provider-delivered brief interventions, and addiction specialty care visits. Other predictors included age, sex, race/ethnicity, neighborhood deprivation index, depression, smoking, substance use disorders, Charlson comorbidity index, prior outpatient visits, insurance type, and medical facility. Cox proportional hazards models were used to compute hazard ratios (HR) for the outcomes of time to unhealthy alcohol use screening and time to first addiction specialty visit. Poisson regression with robust standard errors was used to compute prevalence ratios (PR) for other outcomes. RESULTS: 11,235 PLWH and 227,320 HIV-uninfected participants were included. By 4.5 years after baseline, most participants were screened for unhealthy alcohol use (85% of PLWH and 93% of HIV-uninfected), but with a lower rate among PLWH (adjusted HR 0.84, 95% CI 0.82 to 0.85). PLWH were less likely, compared with HIV-uninfected participants, to report unhealthy drinking among those screened (adjusted PR 0.74, 95% CI 0.69 to 0.79), and among those who screened positive, less likely to receive brief interventions (adjusted PR 0.82, 95% CI 0.75 to 0.90), but more likely (adjusted HR 1.7, 95% CI 1.2 to 2.4) to have an addiction specialty visit within 1 year. CONCLUSIONS: Unhealthy alcohol use was lower in PLWH, but the treatment approach by HIV status differed. PLWH reporting unhealthy alcohol use received less brief interventions and more addiction specialty care than HIV-uninfected participants.

Trends in the Molecular Epidemiology and Genetic Mechanisms of Transmitted Human Immunodeficiency Virus Type 1 Drug Resistance in a Large US Clinic Population.

Background: There are few large studies of transmitted drug resistance (TDR) prevalence and the drug resistance mutations (DRMs) responsible for TDR in the United States. Methods: Human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) and protease sequences were obtained from 4253 antiretroviral therapy (ART)-naive individuals in a California clinic population from 2003 to 2016. Phylogenetic analyses were performed to study linkages between TDR strains and selection pressure on TDR-associated DRMs. Results: From 2003 to 2016, there was a significant increase in overall (odds ratio [OR], 1.05 per year [95% confidence interval {CI}, 1.03-1.08]; P < .001) and nonnucleoside RT inhibitor (NNRTI)-associated TDR (OR, 1.11 per year [95% CI, 1.08-1.15]; P < .001). Between 2012 and 2016, TDR rates to any drug class ranged from 15.7% to 19.2%, and class-specific rates ranged from 10.0% to 12.8% for NNRTIs, 4.1% to 8.1% for nucleoside RT inhibitors (NRTIs), and 3.6% to 5.2% for protease inhibitors. The thymidine analogue mutations, M184V/I and the tenofovir-associated DRMs K65R and K70E/Q/G/N/T accounted for 82.9%, 7.3%, and 1.4% of NRTI-associated TDR, respectively. Thirty-seven percent of TDR strains clustered with other TDR strains sharing the same DRMs. Conclusions: Although TDR has increased significantly in this large cohort, many TDR strains are unlikely to influence the activity of currently preferred first-line ART regimens. The high proportion of DRMs associated with infrequently used regimens combined with the clustering of TDR strains suggest that some TDR strains are being transmitted between ART-naive individuals.

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.

Improvement of Sexually Transmitted Disease Screening Among HIV-Infected Men Who Have Sex With Men Through Implementation of a Standardized Sexual Risk Assessment Tool.

BACKGROUND: Screening for gonorrhea (GC) and chlamydia (CT) and syphilis among HIV-positive (HIV+) men who have sex with men (MSM) is recommended at least annually. However, significant gaps in screening coverage exist. We conducted a quality improvement intervention to determine whether informing providers of preintervention screening rates and routinizing sexual risk assessment would improve sexually transmitted disease (STD) screening in a large HIV care clinic. METHODS: In partnership with Kaiser Permanente Northern California, we developed and implemented a 10-item assessment addressing sexual and other behavioral risk factors among HIV+ MSM. We analyzed the proportion of patients screened for GC/CT and syphilis in a preintervention period (June 25-September 26, 2012) and during the intervention period (June 25-September 26, 2013). RESULTS: Of 364 HIV+ MSM seen for care during the intervention period, 47.3% completed the sexual risk assessment. Improvements in GC/CT screening and syphilis screening were observed; when comparing the preintervention period with the intervention period, the proportion of HIV+ MSM receiving GC/CT screening increased by 26.8% (31.6%-40.1%, P = 0.01) at any anatomical site and by 45% (19.5%-28.3%, P = 0.003) at the pharyngeal site. Syphilis screening significantly increased by 18.8% (48.7%-58.0%, P = 0.009). CONCLUSIONS: Overall STD screening increases were observed after this intervention that included didactic training on the urgency of STD screening needs for HIV+ MSM, a presentation of preintervention clinic STD screening data, and the implementation of self-reported sexual risk assessment. Additional efforts are needed to determine feasible ways to accurately assess the appropriateness of STD screening and success of interventions to improve STD screening.

Using a report card to increase HIV screening in a large primary care group practice.

BACKGROUND: Despite increased efforts to promote HIV screening, a large proportion of the US population have never been tested for HIV. OBJECTIVE: To determine whether provider education and personalised HIV screening report cards can increase HIV screening rates within a large integrated healthcare system. DESIGN: This quality improvement study provided a cohort of primary care physicians (PCPs) a brief educational intervention and personalised HIV screening report cards with quarterly performance data. PARTICIPANTS: Participants included a volunteer cohort of 20 PCPs in the department of adult and family medicine. MAIN MEASURES: Per cent of empaneled patients screened for HIV by cohort PCPs compared with PCPs at the Kaiser Permanente Oakland Medical Center (KPOAK) and the non-Oakland Medical Centers in Northern California region (Kaiser Permanente Northern California (KPNC)). KEY RESULTS: Of the 20 participating PCPs, 13 were female and 7 were male. Thirteen were internal medicine and seven family medicine physicians. The average age was 40 years and average practice experience was 9 years after residency. During the 12-month intervention, the estimated increase in HIV screening in the cohort PCP group was 2.6% as compared with 1.9% for KPOAK and 1.8% for KPNC. CONCLUSIONS: These findings suggest that performance-related report cards are associated with modestly increased rates of HIV screening by PCPs.

Virological Failure and Acquired Genotypic Resistance Associated With Contemporary Antiretroviral Treatment Regimens.

BACKGROUND: There are few descriptions of virologic failure (VF) and acquired drug resistance (HIVDR) in large cohorts initiating contemporary antiretroviral therapy (ART). METHODS: We studied all persons with HIV (PWH) in a California clinic population initiating ART between 2010 and 2017. VF was defined as not attaining virologic suppression, discontinuing ART, or virologic rebound prompting change in ART. RESULTS: During the study, 2315 PWH began ART. Six companion drugs were used in 93.3% of regimens: efavirenz, elvitegravir/c, dolutegravir, b-darunavir, rilpivirine, and raltegravir. During a median follow-up of 36 months, 214 (9.2%) PWH experienced VF (2.8 per 100 person-years) and 62 (2.7%) experienced HIVDR (0.8 per 100 person-years). In multivariable analyses, younger age, lower CD4 count, higher virus load, and b-atazanavir were associated with increased VF risk; lower CD4 count, higher virus load, and nevirapine were associated with increased HIVDR risk. Compared with efavirenz, dolutegravir, raltegravir, and b-darunavir were associated with reduced HIVDR risk. Risks of VF and HIVDR were not significantly associated with ART initiation year. Of the 62 PWH with HIVDR, 42 received an non-nucleoside RT inhibitor (NNRTI), 15 an integrase-strand transfer inhibitor (INSTI), and 5 a protease inhibitor (PI). Among those with HIVDR on an NNRTI or first-generation INSTI, 59% acquired dual class resistance and 29% developed tenofovir resistance; those receiving a PI or dolutegravir developed just M184V. CONCLUSIONS: Despite the frequent use of contemporary ART regimens, VF and HIVDR continue to occur. Further efforts are required to improve long-term ART virological responses to prevent the consequences of ongoing HIV-1 replication including virus transmission and HIVDR.

Eosinophilic meningitis due to Angiostrongylus and Gnathostoma species.

Eosinophilic meningitis can be the result of noninfectious causes and infectious agents. Among the infectious agents, Angiostrongylus cantonensis and Gnathostoma spinigerum are the most common. Although angiostrongyliasis and gnathostomiasis are not common in the United States, international travel and immigration make these diseases clinically relevant. Both A. cantonensis and G. spinigerum infection can present as severe CNS compromise. Diagnoses of both infections can be challenging and are often clinical because of a paucity of serological assays readily available in the United States. Furthermore, there are conflicting recommendations about treatment for angiostrongyliasis and gnathostomiasis. To further explore the emerging nature of these helminthic infections, a case description and review of A. cantonensis and G. spinigerum infections are presented. The clinical severity of eosinophilic meningitis and diagnosis of these infections are highlighted.

National and International Dimensions of Human Immunodeficiency Virus-1 Sequence Clusters in a Northern California Clinical Cohort.

BACKGROUND: Recent advances in high-throughput molecular epidemiology are transforming the analysis of viral infections. METHODS: Human immunodeficiency virus (HIV)-1 pol sequences from a Northern Californian cohort (NCC) of 4553 antiretroviral-naive individuals sampled between 1998 and 2016 were analyzed together with 140 000 previously published global pol sequences. The HIV-TRAnsmission Cluster Engine (HIV-TRACE) was used to infer a transmission network comprising links between NCC and previously published sequences having a genetic distance ≤1.5%. RESULTS: Twenty-five percent of NCC sequences were included in 264 clusters linked to a published sequence, and approximately one third of these (8.0% of the total) were linked to 1 or more non-US sequences. The largest cluster, containing 512 NCC sequences (11.2% of the total), comprised the subtype B lineage that traced its origin to the earliest North American sequences. Approximately 5 percent of NCC sequences belonged to a non-B subtype, and these were more likely to cluster with a non-US sequence. Twenty-two NCC sequences belonged to 1 of 4 large clusters containing sequences from rapidly growing regional epidemics: CRF07_BC (East Asia), subtype A6 (former Soviet Union), a Japanese subtype B lineage, and an East/Southeast Asian CRF01_AE lineage. Bayesian phylogenetics suggested that most non-B sequences resulted from separate introductions but that local spread within the largest CRF01_AE cluster occurred twice. CONCLUSIONS: The NCC contains national and international links to previously published sequences including many to the subtype B strain that originated in North America and several to rapidly growing Asian epidemics. Despite their rapid regional growth, the Asian epidemic strains demonstrated limited NCC spread.

Implementing electronic substance use disorder and depression and anxiety screening and behavioral interventions in primary care clinics serving people with HIV: Protocol for the Promoting Access to Care Engagement (PACE) trial.

BACKGROUND: Substance use disorders (SUDs) and psychiatric disorders are common among people with HIV (PWH) and lead to poor outcomes. Yet these conditions often go unrecognized and untreated in primary care. METHODS: The Promoting Access to Care Engagement (PACE) trial currently in process examines the impact of self-administered electronic screening for SUD risk, depression and anxiety in three large Kaiser Permanente Northern California primary care clinics serving over 5000 PWH. Screening uses validated measures (Tobacco, Alcohol, Prescription medication, and other Substance use [TAPS]; and the Adult Outcomes Questionnaire [AOQ], which includes the Patient Health Questionnaire [PHQ-9] and Generalized Anxiety Disorder [GAD-2]) delivered via three modalities (secure messaging, tablets in waiting rooms, and desktop computers in exam rooms). Results are integrated automatically into the electronic health record. Based on screening results and physician referrals, behavioral health specialists embedded in primary care initiate motivational interviewing- and cognitive behavioral therapy-based brief treatment and link patients to addiction and psychiatry clinics as needed. Analyses examine implementation (screening and treatment rates) and effectiveness (SUD, depression and anxiety symptoms; HIV viral control) outcomes using a stepped-wedge design, with a 12-month intervention phase implemented sequentially in the clinics, and a 24-month usual care period prior to implementation in each clinic functioning as sequential observational phases for comparison. We also evaluate screening and treatment costs and implementation barriers and facilitators. DISCUSSION: The study examines innovative, technology-facilitated strategies for improving assessment and treatment in primary care. Results may help to inform substance use, mental health, and HIV services. TRIAL REGISTRATION: NCT03217058.

HIV-1 drug resistance genotype results in patients with plasma samples with HIV-1 RNA levels less than 75 copies/mL.

HIV-1 genotypic resistance test results were obtained on clinical samples from 116 patients with plasma HIV-1 RNA levels of less than 75 copies/mL. Genotype validity was confirmed in 49 of 50 patients with a previous or follow-up genotype. The belief that genotypic resistance testing is unreliable in samples with low-level viremia should be reassessed.

HIV-1 Protease and reverse-transcriptase mutations: correlations with antiretroviral therapy in subtype B isolates and implications for drug-resistance surveillance.

Background. It is important, for drug-resistance surveillance, to identify human immunodeficiency virus type 1 (HIV-1) strains that have undergone antiretroviral drug selection.Methods. We compared the prevalence of protease and reverse-transcriptase (RT) mutations in HIV-1 sequences from persons with and without previous treatment with protease inhibitors (PIs), nucleoside RT inhibitors (NRTIs), and nonnucleoside RT inhibitors (NNRTIs). Treatment-associated mutations in protease isolates from 5867 persons and RT isolates from 6247 persons were categorized by whether they were polymorphic (prevalence, >0.5%) in untreated individuals and whether they were established drug-resistance mutations. New methods were introduced to minimize misclassification from transmitted resistance, population stratification, sequencing artifacts, and multiple hypothesis testing.Results. Some 36 established and 24 additional nonpolymorphic protease mutations at 34 positions were related to PI treatment, 21 established and 22 additional nonpolymorphic RT mutations at 24 positions with NRTI treatment, and 15 established and 11 additional nonpolymorphic RT mutations at 15 positions with NNRTI treatment. In addition, 11 PI-associated and 1 NRTI-associated established mutations were polymorphic in viruses from untreated persons.Conclusions. Established drug-resistance mutations encompass only a subset of treatment-associated mutations; some of these are polymorphic in untreated persons. In contrast, nonpolymorphic treatment-associated mutations may be more sensitive and specific markers of transmitted HIV-1 drug resistance.