Faculty Bibliography

BACKGROUND:Of new sexually transmitted infections (STIs) in the US, 50% occur among youth aged 15-24 years. Previous studies among youth with HIV (YHIV) do not distinguish STI trends among individuals with perinatally (YPHIV) and non-perinatally (YNPHIV) acquired HIV. METHODS:Among three Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) Studies conducted between 2009-2015, we estimated incident diagnoses of trichomonal, bacterial, viral, and overall STIs stratified by sex assigned at birth, mode of HIV acquisition (perinatal (YPHIV) and non-perinatal (YNPHIV)), age (13-17 and 18-24 years), CD4 count (<200, 200-499, and ≥ 500/μL), and HIV viral load (VL) (<, ≥400 copies/mL). RESULTS:Among 3,131 YHIV, across the three studies, mean age (SD) was 20.6 (2.6) years, 888 (28%) were female, 2,498 (80%) had non-perinatal HIV acquisition recorded, and 2,298 (73%) were African American/Black. Mean follow-up was 0.9 (0.3) years. YNPHIV, compared to YPHIV, spent less person-time with VL <400 copies/mL (47% vs. 53%), more time off antiretroviral therapy (49% vs. 15%) and had higher overall STI rates (males: 65.9 vs. 8.5/100PY; females: 54.7 vs. 17.2/100 PY). Among YPHIV, bacterial STIs were higher during person-time spent with VL ≥ vs. <400 copies/mL (male YPHIV: 10.9 vs. 0.6/100PY; female YPHIV: 11.2 vs. 2.9/100PY); no difference was observed among YNPHIV which may be due to concurrent acquisition of HIV and other STIs and limited follow-up. CONCLUSIONS:Compared to YPHIV, YNPHIV spent less time on ART and virologically suppressed; YNPHIV also had higher STI diagnosis rates. Very high STI diagnosis rates among youth with HIV, including among those without virologic suppression, highlight the importance of youth-focused efforts to support durable virologic suppression and identify and treat STIs.

Importance/UNASSIGNED:Hospital consolidations have been shown not to improve quality on average. Objective/UNASSIGNED:To assess a full-integration approach to hospital mergers based on quality metrics in a safety net hospital acquired by an urban academic health system. Design, Setting, and Participants/UNASSIGNED:This quality improvement study analyzed outcomes for all nonpsychiatric, nonrehabilitation, non-newborn patients discharged between September 1, 2010, and August 31, 2019, at a US safety net hospital that was acquired by an urban academic health system in January 2016. Interrupted time series and statistical process control analyses were used to assess the main outcomes and measures. Data sources included the hospital's electronic health record, Centers for Medicare & Medicaid Services Hospital Compare, and nursing quality reports. Exposures/UNASSIGNED:A full-integration approach to the merger that included: (1) early administrative and clinical leadership integration with the academic health system; (2) rapid transition to the academic health system electronic health record; (3) local ownership of quality metrics; (4) system-level goals with real-time actionable analytics through combined dashboards; and (5) implementation of value-based and other analytic-driven interventions. Main Outcomes and Measures/UNASSIGNED:The primary outcome was in-hospital mortality. Secondary outcomes included 30-day readmission, patient experience, and hospital-acquired conditions. Results/UNASSIGNED:The 122 348 patients in the premerger (September 2010 through August 2016) and the 58 904 patients in the postmerger (September 2016 through August 2019) periods had a mean (SD) age of 55.5 (22.0) years; the total sample of 181 252 patients included 112 191 women (61.9%), the payor mix was majority governmental (144 375 patients [79.7%]), and most admissions were emergent (121 469 patients [67.0%]). There was a 0.71% (95% CI, 0.57%-0.86%) absolute (27% relative) reduction in the crude mortality rate and 0.95% (95% CI, 0.83%-1.12%) absolute (33% relative) in the adjusted rate by the end of the 3-year intervention period. There was no significant improvement in readmission rates after accounting for baseline trends. There were fewer central line infections per 1000 catheter days, fewer catheter-associated urinary tract infections per 1000 discharges, and a higher likelihood of patients recommending the hospital or ranking it 9 or 10. Conclusions and Relevance/UNASSIGNED:In this quality improvement study, a hospital merger with a full-integration approach to consolidation was found to be associated with improvement in quality outcomes.

BACKGROUND:Men who have sex with men (MSM) are at high risk for human papillomavirus (HPV)-related anal cancer. Little is known about the prevalence of low-grade squamous intraepithelial lesions (LSILs) and the anal cancer precursor, high-grade squamous intraepithelial lesions (HSILs), among young MSM with HIV (MSMLWH). HPV vaccination is recommended in this group, but its safety, immunogenicity, and protection against vaccine-type HPV infection and associated LSILs/HSILs have not been studied. METHODS:Two hundred and sixty MSMLWH aged 18-26 years were screened at 17 US sites for a clinical trial of the quadrivalent (HPV6,11,16,18) HPV (qHPV) vaccine. Those without HSILs were vaccinated at 0, 2, and 6 months. Cytology, high-resolution anoscopy with biopsies of lesions, serology, and HPV testing of the mouth/penis/scrotum/anus/perianus were performed at screening/month 0 and months 7, 12, and 24. RESULTS:Among 260 MSMLWH screened, the most common reason for exclusion was detection of HSILs in 88/260 (34%). 144 MSMLWH were enrolled. 47% of enrollees were previously exposed to HPV16. No incident qHPV type-associated anal LSILs/HSILs were detected among men naive to that type, compared with 11.1, 2.2, 4.5, and 2.8 cases/100 person-years for HPV6,11,16,18-associated LSILs/HSILs, respectively, among those previously exposed to that type. qHPV was immunogenic and safe with no vaccine-associated serious adverse events. CONCLUSIONS:18-26-year-old MSMLWH naive to qHPV vaccine types were protected against incident qHPV type-associated LSILs/HSILs. Given their high prevalence of HSILs, there is an urgent need to vaccinate young MSMLWH before exposure to vaccine HPV types, before initiating sexual activity, and to perform catch-up vaccination.

Early reports showed high mortality from coronavirus disease 2019 (COVID-19). Mortality rates have recently been lower, raising hope that treatments have improved. However, patients are also now younger, with fewer comorbidities. We explored whether hospital mortality was associated with changing demographics at a 3-hospital academic health system in New York. We examined in-hospital mortality or discharge to hospice from March through August 2020, adjusted for demographic and clinical factors, including comorbidities, admission vital signs, and laboratory results. Among 5,121 hospitalizations, adjusted mortality dropped from 25.6% (95% CI, 23.2-28.1) in March to 7.6% (95% CI, 2.5-17.8) in August. The standardized mortality ratio dropped from 1.26 (95% CI, 1.15-1.39) in March to 0.38 (95% CI, 0.12-0.88) in August, at which time the average probability of death (average marginal effect) was 18.2 percentage points lower than in March. Data from one health system suggest that mortality from COVID-19 is decreasing even after accounting for patient characteristics.

OBJECTIVE:To define inflammatory pathways in youth living with HIV infection (YLWH), assessments of biomarkers associated with lymphocyte and macrophage activation, vascular injury, or bone metabolism were performed in YLWH in comparison with healthy controls (HC). DESIGN/METHODS: Longitudinal multicenter study comparing biomarkers in YLWH suppressed on antiretroviral therapy (ART), those with ongoing viral replication, and HC were compared using single blood samples obtained at end of study. METHODS: Twenty-three plasma proteins were measured by ELISA or multiplex assays. Principal component analysis (PCA) was used to define contributions of individual biomarkers to define outcome groups. RESULTS: The study cohort included 129 predominantly African American, male participants, 21-25 years old at entry. Nine biomarkers of lymphocyte and macrophage activation and cardiovascular injury differed between HC and YLWH. Significant positive correlations were identified between lymphocyte and macrophage activation biomarkers among HC and YLWH. Correlations distinct to YLWH were predominantly between biomarkers of macrophage and vascular inflammation. PCA of outcome groups showed HC and suppressed YLWH clustering together for lymphocyte activation biomarkers, whereas macrophage activation markers showed all YLWH clustering distinct from HC. Cardiovascular biomarkers were indistinguishable across groups. Averaged variable importance projection to assess single biomarkers that maximally contribute to discriminate among outcome groups identified soluble CD27, CD14, and CD163 as the 3 most important with TNFα and LPS also highly relevant in providing separation. CONCLUSIONS: Soluble inflammatory and lymphocyte biomarkers sufficiently distinguish YLWH from HC. Persistent macrophage activation biomarkers may provide a means to monitor consequences of HIV infection in fully suppressed YLWH.

BACKGROUND: Beneficial HIV treatment outcomes require success at multiple steps along the HIV Continuum of Care. Youth living with HIV are a key population, and sites in the Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) are known for modeling optimum HIV adolescent care. METHODS: A longitudinal cohort study conducted at 14 network sites across the United States assessed how the later steps of the Continuum of Care were achieved among youth: engagement, treatment and viral load suppression. Youth aged 13-24 who were behaviorally-infected with HIV and linked to care at an ATN-affiliated site were eligible to participate. RESULTS: A total of 467 youth were enrolled and had one year of available data. Most were ages 22-24 (57%), male (79%), and black/non-Hispanic (71%). Most used alcohol (81%) and marijuana (61%) in the three months prior to enrollment, and 40% had a history of incarceration. Among this cohort of youth, 86% met criteria for care engagement; among these, 98% were prescribed antiretroviral therapy and 89% achieved viral load suppression. Sustained viral load suppression at all measured time points was found among 59% with initial suppression. Site characteristics were notable for prevalence of adherence counseling (100%), case management (100%), clinicbased mental health (93%) and substance use (64%) treatment. CONCLUSIONS: Youth living with HIV in the United States can be successfully treated at health care sites with experience, excellence, and important resources and services. Sustained viral load suppression may be an important step to add to the Continuum of Care for youth.

BACKGROUND:Identifying factors associated with partner notification among youth living with HIV is critical for effective HIV prevention and treatment strategies. METHODS:A total of 924 male and female behaviorally infected youth aged 13-24 across 14 U.S. cities completed an audio computer-assisted self-interview including questions about demographics and experiences with patient- and provider-referral partner notification. RESULTS:The majority of participants self-identified as male (82.5%), Black/non-Hispanic (70.1%), and Hispanic/Latino (18.2%). Most males (93.4%) reported engaging in male-to-male sexual contact. Over three-quarters (77.6%) reported that all or some of their partners were contacted, while 22.4% indicated that none were contacted regarding potential HIV exposure. Most (52.4%) reported that only one person talked to them about notifying partners including the HIV tester (36.5%) followed by their health care provider/doctor (27.6%). Less than a fifth (18.3%) were themselves notified of their own exposure to HIV. Using multivariable logistic regression, 3 factors were associated with successful partner notification: (1) when more than one person talked to participants about partner notification (AOR = 1.87, 1.33-2.62); (2) if they themselves had been notified of their own HIV exposure (AOR = 1.83, 1.13-2.95); and (3) if their education included some college or technical school versus less than high school (AOR = 1.72, 1.04-2.85). CONCLUSIONS:Partner notification among youth living with HIV is unsuccessful at least 22.4% of the time, although minimal criteria for partner services are being met almost universally. Partner notification might benefit from enhanced guidelines that call for both HIV testers and HIV care providers to discuss this important strategy with HIV-positive youth.

Identifying risk and protective factors associated with condomless sex among youth living with HIV is imperative for developing effective HIV prevention strategies. A cross-sectional sample of 1728 participants, 12-26 years of age, recruited from adolescent medicine clinics in 17 U.S. cities completed an audio-computer assisted self-interview with questions about their substance use, psychosocial factors, and attitudinal and behavioral factors. Guided by syndemics theory, a path analysis was used to assess the interrelations of these factors. Analyses of model fit statistics indicated statistically significant direct pathways between substance use, psychosocial factors, self-efficacy for risk-reduction, alternative risk-reduction attitudes and behaviors and condomless sex. The total indirect effect of self-efficacy for risk-reduction on condomless sex through alternative risk-reduction attitudes and behaviors was also significant. Multi-faceted, tailored interventions that address individual risk and protective factors and their combined synergistic effects are urgently needed to prevent condomless sex among this population.

BACKGROUND: Young men who have sex with men (YMSM) are a key population for implementation of preexposure prophylaxis (PrEP) interventions. This open-label study examined adherence to PrEP and assessed sexual behavior among a diverse sample of YMSM in 12 US cities. METHODS: Eligible participants were 18- to 22-year-old HIV-uninfected MSM who reported HIV transmission risk behavior in the previous 6 months. Participants were provided daily tenofovir disoproxil fumarate/emtricitabine (Truvada). Study visits occurred at baseline, monthly through week 12, and then quarterly through week 48. Dried blood spots were serially collected for the quantification of tenofovir diphosphate (TFV-DP). RESULTS: Between March and September 2013, 2186 individuals were approached and 400 were found to be preliminarily eligible. Of those 400, 277 were scheduled for an in-person screening visit and 200 were enrolled (mean age = 20.2; 54.5% black, 26.5% Latino). Diagnosis of sexually transmitted infections, including urethral and rectal chlamydial/gonococcal infection and syphilis, at baseline was 22% and remained high across visits. At week 4, 56% of participants had TFV-DP levels consistent with >/=4 pills per week. By week 48, 34% of participants had TFV-DP levels consistent with >/=4 pills per week, with a noticeable drop-off occurring at week 24. Four HIV seroconversions occurred on study (3.29/100 person-years). Condomless sex was reported by >80% of participants, and condomless anal sex with last partner was associated with higher TFV-DP levels. CONCLUSIONS: Acceptability of PrEP was high, and most participants achieved protective drug levels during monthly visits. As visit frequency decreased, so did adherence. YMSM in the United States may need PrEP access in youth-friendly settings with tailored adherence support and potentially augmented visit schedules.

Human papillomavirus (HPV), Epstein-Barr virus (EBV), and Kaposi sarcoma-associated herpes virus (KSHV) may promote oral cancers, especially among immunosuppressed individuals. The aims of this study were to examine whether demographic characteristics, medical history, sexual behaviors, substance use, CD4+ T-cell count, HIV viral load, and HPV vaccination were associated with HPV, EBV and KSHV infection and viral load. Multivariable modeling using logistic or linear regression examined associations between independent variables and infection or viral load, respectively. Among 272 HIV-infected 12-24 year-old youth, 19.5% were positive for oral HPV, 88.2% for EBV, and 11.8% for KSHV. In multivariable models, recent marijuana use (OR 1.97, 95% CI 1.02-3.82) and lower CD4+ T-cell count (< 350 vs. > 350 cells/mm3 : OR 1.92, 95% CI 1.003-3.69) were associated with HPV infection; lifetime tobacco use (estimated coefficient [EC] 1.55, standard error [SE] 0.53, p =.0052) with HPV viral load; recent tobacco use (OR 2.90, 95% CI 1.06-7.97) and higher HIV viral load (> 400 vs. < 400 copies/mL: OR 3.98, 95% CI 1.84-8.74) with EBV infection; Black vs. White race (EC 1.18, SE 0.37, p =.0023) and lower CD4+ T-cell count (EC 0.70, SE 0.28, p =.017) with EBV viral load, male vs. female gender (OR 10, 95% CI 1.32-100) with KSHV infection, and younger age at HIV diagnosis (1-14 vs. 18-20 years: EC 0.33, SE 0.16, p =.049; 15-17 vs. 18-20 years: EC 0.35, SE 0.13, p =.0099) with KSHV viral load. In conclusion, substance use and immunosuppression are associated with oral DNA tumor viruses in HIV-infected youth