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Rates of sexually transmitted infection diagnoses among US youth with perinatally- and non-perinatally acquired HIV

Neilan, Anne M; DeMonte, Justin B; Foote, Julia H A; Karalius, Brad; Patel, Kunjal; Kapogiannis, Bill G; Rudy, Bret J; Huszti, Heather; Fernandez, M Isabel; Hudgens, Michael G; Ciaranello, Andrea L
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.
PMID: 34711773
ISSN: 1537-4521
CID: 5042752

High Prevalence of Anal High-Grade Squamous Intraepithelial Lesions, and Prevention Through Human Papillomavirus Vaccination, in Young Men Who Have Sex With Men Living With Human Immunodeficiency Virus

Palefsky, Joel M; Lensing, Shelly Y; Belzer, Marvin; Lee, Jeannette; Gaur, Aditya H; Mayer, Kenneth; Futterman, Donna; Stier, Elizabeth A; Paul, Mary E; Chiao, Elizabeth Y; Reirden, Daniel; Goldstone, Stephen E; Tirado, Maribel; Cachay, Edward R; Barroso, Luis F; Da Costa, Maria; Darragh, Teresa M; Rudy, Bret J; Wilson, Craig M; Kahn, Jessic A
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.
PMID: 33991185
ISSN: 1537-6591
CID: 5038802

Trends in COVID-19 Risk-Adjusted Mortality Rates

Horwitz, Leora I; Jones, Simon A; Cerfolio, Robert J; Francois, Fritz; Greco, Joseph; Rudy, Bret; Petrilli, Christopher M
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.
PMID: 33147129
ISSN: 1553-5606
CID: 4664172

Soluble CD14, CD163, and CD27 biomarkers distinguish ART-suppressed youth living with HIV from healthy controls

Williams, Julie C; Zhang, Xinrui; Karki, Manju; Chi, Yueh-Yun; Wallet, Shannon M; Rudy, Bret J; Nichols, Sharon L; Goodenow, Maureen M; Sleasman, John W
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.
PMID: 29377283
ISSN: 1938-3673
CID: 2933682

HIV Continuum of Care for Youth in the United States

Lally, Michelle A; van den Berg, Jacob J; Westfall, Andrew O; Rudy, Bret J; Hosek, Sybil G; Fortenberry, J Dennis; Monte, Dina; Tanney, Mary R; McFarland, Elizabeth J; Xu, Jiahong; Kapogiannis, Bill G; Wilson, Craig M
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.
PMID: 28991884
ISSN: 1944-7884
CID: 2732392

Partner Notification for Youth Living With HIV in 14 Cities in the United States

van den Berg, Jacob J; Javanbakht, Marjan; Gorbach, Pamina M; Rudy, Bret J; Westfall, Andrew O; Wilson, Craig M; Lally, Michelle A
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.
PMID: 29023252
ISSN: 1944-7884
CID: 2922202

Using Syndemics Theory to Investigate Risk and Protective Factors Associated with Condomless Sex Among Youth Living with HIV in 17 U.S. Cities

van den Berg, Jacob J; Isabel Fernandez, M; Fava, Joseph L; Operario, Don; Rudy, Bret J; Wilson, Patrick A
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.
PMID: 27624727
ISSN: 1573-3254
CID: 2246962

An HIV Preexposure Prophylaxis Demonstration Project and Safety Study for Young MSM

Hosek, Sybil G; Rudy, Bret; Landovitz, Raphael; Kapogiannis, Bill; Siberry, George; Rutledge, Brandy; Liu, Nancy; Brothers, Jennifer; Mulligan, Kathleen; Zimet, Gregory; Lally, Michelle; Mayer, Kenneth H; Anderson, Peter; Kiser, Jennifer; Rooney, James F; Wilson, Craig M
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.
PMID: 27632233
ISSN: 1944-7884
CID: 2352962

Prevalence and risk factors for oral DNA tumor viruses in HIV-infected youth

Kahn, Jessica A; Rudy, Bret J; Xu, Jiahong; Kapogiannis, Bill; Secord, Elizabeth; Gillison, Maura
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
PMID: 27096166
ISSN: 1096-9071
CID: 2080042

Persistently activated CD27+CD80+ B cells following art correlate with macrophage activation [Meeting Abstract]

Hudey, S N; Rudy, B J; Zhang, X; Lukas, S; Goodenow, M; Sleasman, J
Background: Antiretroviral therapy (ART) and control of HIV replication does not fully restore perturbations within resting (CD19+CD27+CD21+) and activated (CD19+CD27+CD80+) memory B cell compartments. This study was based on the hypothesis that ongoing macrophage activation and HIVassociated inflammation contributes to B cell abnormalities. Methodology: Longitudinal cellular and soluble plasma markers for inflammation were evaluated in 43 healthy controls (HC) and 17 behaviorally-infected HIV-1+ subjects ages 18-25 years. Multicolor flow cytometry analysis of B cell subsets and assessment of markers of macrophage (sCD163 and sCD14) and lymphocyte (sCD27) were measured by ELISA. Assays were performed prior to and at 24 and 48 weeks following ART. All HIV-1 subjects suppressed HIV to < 50 copies/ml. Healthy controls and HIV+ treated subjects were also compared pair-wise and longitudinally at study entry (prior to ART), 24 weeks and 48 weeks on therapy by non-parametric rank sum. Results: Compared to HC, resting memory B cells were lower and activated B cells were higher among HIV+ subjects at all time points before and after ART {22.6 +/- 8.1% (HC) versus 16.4 +/- 6.7% (HIV+ at 48 weeks) for resting memory, p=0.0081, and 11.5 +/- 5.3% (HC) versus 15.2 +/- 5.1% (HIV+ at 48 weeks), for activated B cells, p=0.0415, Mann-Whitney}, Control of viral replication failed to decrease the proportions of activated B cells or increase memory B cells after 48 weeks on therapy. Compared to HC, sCD14, sCD27 and sCD163 all remained significantly elevated in HIV+ subjects at 48 weeks following therapy (p=0.0027, p<0.0001, and p=0.0142, respectively, Mann-Whitney). Regression analysis revealed a positive correlation between the decrease in resting memory B cells and levels of sCD14 at 48 weeks on therapy (r=0.51, p=0.038, Spearman test) but sCD163 and sCD27 did not correlate with the extent of B cell activation. Results also showed a positive correlation between the increase in activated B cells and the elevation of sCD14 24 weeks following therapy (r=0.54, p=0.028 Spearman). Conclusions: Elevated levels of sCD14, a biomarker of macrophage activation, is the result of LPS binding to TLR4. Our results show that chronic B cell activation also reflects ongoing inflammation due to microbial translocation that may contributes to ongoing B cell dysfunction, even in HIV-infected subjects who control viral replication with ART
ISSN: 2161-5861
CID: 1806602