Optimizing Screening for Anorectal, Pharyngeal, and Urogenital Chlamydia trachomatis and Neisseria gonorrhoeae Infections in At-Risk Adolescents and Young Adults in New Orleans, Louisiana and Los Angeles, California, United States.

BACKGROUND: Public health organizations have inconsistent recommendations for screening adolescents and young adults for Chlamydia trachomatis and Neisseria gonorrhoeae infections. Guidelines suggest different combinations of anorectal, pharyngeal, and urogenital testing based on age, sex, and sexual activity. Further evaluation of how identity and behaviors impact the anatomic distribution of C. trachomatis and N. gonorrhoeae infection is needed to optimize future screening practices. METHODS: We assessed the positivity of C. trachomatis and N. gonorrhoeae infections at different anatomic sites in a cohort of at-risk sexually active adolescents and young adults aged 12-24 years in New Orleans, Louisiana and Los Angeles, California. Participants were tested for C. trachomatis and N. gonorrhoeae at 3 sites (anorectum, pharynx, and urethral/cervix) every 4 months using self-collected swabs. We stratified anatomic distributions of infection into 4 gender and sexual behavior categories: (1) cisgender men who have sex with men and transgender women (MSMTW); (2) cisgender heterosexual males; (3) cisgender heterosexual females; and (4) gender minorities assigned female at birth. RESULTS: While three-site testing detected all infections, two-site (anorectum and urethra/cervix) testing identified 92%-100% of C. trachomatis or N. gonorrhoeae infections in participants assigned female at birth and cisgender heterosexual males. For MSMTW, two-site anorectal and pharyngeal testing vs single-site anorectal testing increased the proportion of individuals with either infection from 74% to 93%. CONCLUSIONS: Sexual behavior and gender identity may influence detection of C. trachomatis and N. gonorrhoeae infections at specific anatomic testing sites. Testing guidelines should incorporate sexual behavior and gender identity. CLINICAL TRIALS REGISTRATION: NCT03134833.

Safety and Effectiveness of Same-Day Chlamydia trachomatis and Neisseria gonorrhoeae Screening and Treatment Among Gay, Bisexual, Transgender, and Homeless Youth in Los Angeles, California, and New Orleans, Louisiana.

BACKGROUND: Gay, bisexual, transgender, and homeless youth are at risk of sexually transmitted infections. As part of an adolescent human immunodeficiency virus prevention study, we provided same-day Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) testing and treatment. We aimed to evaluate the feasibility and effectiveness of same-day CT and NG treatment on the proportion of participants receiving timely treatment. METHODS: We recruited adolescents with high sexual risk behaviors aged 12 to 24 years from homeless shelters, lesbian, gay, bisexual, and transgender organizations, and community health centers in Los Angeles, California, and New Orleans, Louisiana from May 2017 to June 2019. Initially, participants were offered point-of-care pharyngeal, rectal, and urethral/vaginal CT and NG testing and referral to another clinic for treatment. After March 2018 in Los Angeles and November 2018 in New Orleans, we provided same-day treatment (and partner treatment packs) for study participants. We measured the proportion of participants who received same-day treatment and the median time to treatment. We collected frequency of partner treatment and any reported adverse treatment-related events. RESULTS: The proportion of participants receiving same-day CT and NG treatment increased from 3.6% (5/140) to 21.1% (20/95; Δ17.5%; 95% confidence interval, 9.2%-26.9%) after implementation of same-day testing and treatment. The median time to treatment decreased from 18.5 to 3 days. Overall, 36 participants took a total of 48 partner treatment packs. There were no reported treatment-related adverse events. CONCLUSIONS: Providing sexually transmitted infection treatment to adolescents at the same visit as testing is feasible and safe, and can increase the proportion of individuals receiving timely treatment.

Sexually Transmitted Infection Positivity Among Adolescents With or at High-Risk for Human Immunodeficiency Virus Infection in Los Angeles and New Orleans.

BACKGROUND: Gay, bisexual, and transgender youth and homeless youth are at high risk for sexually transmitted infections (STIs). However, little recent data exist describing STI positivity by anatomical site among those groups. We determined the positivity of Chlamydia trachomatis (CT) infection, Neisseria gonorrhoeae (NG) infection, and syphilis antibody reactivity among lesbian, gay, bisexual, transgender, and homeless youth. METHODS: We recruited 1,264 adolescents with high risk behavior aged 12 to 24 years from homeless shelters, lesbian, gay, bisexual, and transgender organizations, community health centers, and using social media and online dating apps in Los Angeles, California and New Orleans, Louisiana from May 2017 to February 2019. Participants received point-of-care pharyngeal, rectal, and urethral/vaginal CT and NG testing and syphilis antibody testing. We calculated STI positivity by anatomical site and compared positivity by participant subgroups based on human immunodeficiency virus (HIV) status, sex assigned at birth, and gender identity. RESULTS: CT and NG positivity and syphilis antibody reactivity was higher among HIV-infected adolescent men who have sex with men (MSM) than HIV-uninfected adolescent MSM (40.2% vs. 19%, P < 0.05), particularly CT or NG rectal infection (28% vs. 12.3%, P < 0.05). Of participants with positive CT or NG infections, 65% had extragenital-only infections, 20% had both extragenital and urogenital infections, and 15% had urogenital-only infections. CONCLUSIONS: Sexually transmitted infection positivity was high, particularly among transgender women and MSM. The high proportion of rectal and pharyngeal infections highlights the importance of both urogenital and extragenital STI screening. More accessible STI testing is necessary for high-risk adolescent populations.

Demographics of Youth With Newly Diagnosed Acute/Recent HIV Infection in Adolescent Trials Network 147: Early Treatment of Acute HIV Infection.

PURPOSE: Gay, bisexual, and other cisgender men who have sex with men, and racial minority youth are at elevated risk of acquiring HIV infection. The Adolescent Trials Network 147 recruited youth with acute/recent HIV-infection for early antiretroviral treatment. The cohort make-up is described here. METHODS: Treatment-naïve, recently identified HIV + youth, aged 12-24 years, from Los Angeles and New Orleans were recruited from community centers, clinics, social media, and a high-risk seronegative cohort (n = 1,727, the Adolescent Trials Network 149) using point-of-care assays. Acute HIV infection was determined by Fiebig staging. HIV RNA viral load (VL) and CD4 cell counts, along with demographic and behavioral data were assessed at enrollment. RESULTS: Between July 2017 and July 2021, 103 newly diagnosed youth were enrolled, initiating antiretroviral treatment within a week. Mean age was 20.8 years (standard deviation: 2.4); 90.3% identified as cis male, 83.5% were single or in casual relationships, 71.8% were gay, bisexual, and other cisgender men who have sex with men; 60.2% were Black. One-fourth (24.3%) reported homelessness ever; 10.7% within last 4 months. At enrollment, median plasma VL was 37,313 HIV RNA copies/ml (interquartile range: 5,849-126,162) and median CD4 count 445.5 cells/mm3 (interquartile range: 357-613). 40% of youth reported acute retroviral symptoms before or at enrollment. Acutely infected, seroconverting youth had the highest VL. Sexually transmitted coinfections were present at enrollment in 56% of the cohort, with syphilis being most frequent (39%). DISCUSSION: Early identification and treatment of HIV can increase positive HIV outcomes. A high sexually transmitted infection burden was present in recently HIV-infected youth. Acute retroviral symptoms were not reported by most participants, demonstrating that broad universal HIV screening is needed for identification of recent infection in youth.

Adolescents may accurately self-collect pharyngeal and rectal clinical specimens for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae infection.

BACKGROUND: The COVID-19 pandemic illuminated the benefits of telemedicine. Self-collected specimens are a promising alternative to clinician-collected specimens when in-person testing is not feasible. In this study, we assessed the adequacy of self-collected pharyngeal and rectal specimens for the detection of Chlamydia trachomatis and Neisseria gonorrhoeae among individuals undergoing chlamydia and gonorrhea screening. METHODS: We used data from a large cohort study that included male and female adolescents between the ages of 12-24 years. We considered self-collected specimens adequate for clinical use if the human synthase gene (a control target of the assay) was detected in the specimen. RESULTS: In total, 2,458 specimens were included in the analysis. The human synthase gene was detected in 99.2% (2,439/2,458) of all self-collected specimens, 99.5% (1,108/1,114) of the pharyngeal specimens, and 99.0% (1,331/1,344) of the rectal specimens. CONCLUSION: Self-collected pharyngeal and rectal specimens demonstrated a very high proportion of human gene presence, suggesting that self-collection was accurate. A limitation of this study is that the sample adequacy control detects the presence or absence of the human hydroxymethylbilane synthase gene, but it does not indicate the specific anatomic origin of the human hydroxymethylbilane synthase gene. Self-collected specimens may be an appropriate alternative to clinician-collected specimens.

Community-Based, Point-of-Care Sexually Transmitted Infection Screening Among High-Risk Adolescents in Los Angeles and New Orleans: Protocol for a Mixed-Methods Study.

BACKGROUND: Sexually transmitted infection (STI) rates are increasing in the United States, with approximately half of new infections occurring among adolescents aged 15-24 years. Gay, bisexual, and transgender youth (GBTY), homeless youth, and youth with histories of drug use, mental health disorders, and incarceration are all at uniquely high risk for STIs. However, these adolescents often lack access to sexual health services. OBJECTIVE: This study aims to use point-of-care STI tests in community-based settings to screen for and treat STIs in adolescents. METHODS: We are recruiting 1500 HIV-uninfected youth and 220 HIV-infected youth from homeless shelters, GBTY organizations, and community health centers in Los Angeles, California and New Orleans, Louisiana. Study participants will receive STI screening every 4 months for 24 months. STI screening includes rapid HIV, syphilis, Chlamydia trachomatis, Neisseria gonorrhoeae, and Hepatitis C virus testing. Trained paraprofessionals will conduct all STI testing. When a participant screens positive for an STI, they are either linked to a partner medical clinic or provided with same-day antibiotic therapy and expedited partner therapy. We will monitor STI prevalence among study participants as well as point-of-care test performance, linkage to care, and treatment outcomes. RESULTS: The project was funded in 2016, and enrollment will be completed in 2019. Preliminary data analysis is currently underway. CONCLUSIONS: As STI rates continue to rise, it is important to improve access to screening and treatment services, particularly for high-risk adolescents. In this study, we aim to evaluate the use of point-of-care STI diagnostic tests in community-based organizations. We hope to determine the prevalence of STIs among these adolescents and evaluate the acceptability and feasibility of community-based STI screening and treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT03134833; https://clinicaltrials.gov/ct2/show/NCT03134833. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/10795.

The Stepped Care Intervention to Suppress Viral Load in Youth Living With HIV: Protocol for a Randomized Controlled Trial.

BACKGROUND: Among youth living with HIV (YLH) aged 12-24 years who have health care in the United States, only 30% to 40% are virally suppressed. YLH must achieve viral suppression in order to reduce the probability of infecting others as well as increasing the length and quality of their own life. OBJECTIVE: This randomized controlled trial aimed to evaluate the efficacy of an Enhanced Standard Care condition (n=110) compared to an Enhanced Stepped Care intervention condition (n=110) to increase viral suppression among YLH aged 12-24 years with established infection (not acutely infected). METHODS: YLH (N=220) who are not virally suppressed will be identified at homeless shelters, health clinics, and gay-identified community-based organizations in Los Angeles, CA, and New Orleans, LA. Informed consent will be obtained from all participants. YLH will be randomly assigned to one of two study conditions: Enhanced Standard Care, which includes standard clinical care plus an automated messaging and monitoring intervention (AMMI), or an Enhanced Stepped Care, which includes three levels of intervention (AMMI, Peer Support via social media plus AMMI, or Coaching plus Peer Support and AMMI). The primary outcome is viral suppression of HIV, and YLH will be assessed at 4-month intervals for 24 months. For the Enhanced Stepped Care intervention group, those who do not achieve viral suppression (via blood draw, viral load<200 copies/mL) at any 4-month assessment will "step up" to the next level of intervention. Secondary outcomes will be retention in care, antiretroviral therapy adherence, alcohol use, substance use, sexual behavior, and mental health symptoms. RESULTS: Recruitment for this study began in June 2017 and is ongoing. We estimate data collection to be completed by the end of 2020. CONCLUSIONS: This is the first known application of an Enhanced Stepped Care intervention model for YLH. By providing the lowest level of intervention needed to achieve viral suppression, this model has the potential to be a cost-effective method of helping YLH achieve viral suppression and improve their quality of life. TRIAL REGISTRATION: ClinicalTrials.gov NCT03109431; https://clinicaltrials.gov/ct2/show/NCT03109431. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/10791.

Text-Messaging, Online Peer Support Group, and Coaching Strategies to Optimize the HIV Prevention Continuum for Youth: Protocol for a Randomized Controlled Trial.

BACKGROUND: America's increasing HIV epidemic among youth suggests the need to identify novel strategies to leverage services and settings where youth at high risk (YAHR) for HIV can be engaged in prevention. Scalable, efficacious, and cost-effective strategies are needed, which support youth during developmental transitions when risks arise. Evidence-based behavioral interventions (EBIs) have typically relied on time-limited, scripted, and manualized protocols that were often delivered with low fidelity and lacked evidence for effectiveness. OBJECTIVE: This study aims to examine efficacy, implementation, and cost-effectiveness of easily mountable and adaptable, technology-based behavioral interventions in the context of an enhanced standard of care and study assessments that implement the guidelines of Centers for Disease Control and Prevention (CDC) for routine, repeat HIV, and sexually transmitted infection (STI) testing for high-risk youth. METHODS: Youth aged between 12 and 24 years (n=1500) are being recruited from community-based organizations and clinics serving gay, bisexual, and transgender youth, homeless youth, and postincarcerated youth, with eligibility algorithms weighting African American and Latino youth to reflect disparities in HIV incidence. At baseline and 4-month intervals over 24 months (12 months for lower-risk youth), interviewers monitor uptake of HIV prevention continuum steps (linkage to health care, use of pre- or postexposure prophylaxis, condoms, and prevention services) and secondary outcomes of substance use, mental health, and housing security. Assessments include rapid diagnostic tests for HIV, STIs, drugs, and alcohol. The study is powered to detect modest intervention effects among gay or bisexual male and transgender youth with 70% retention. Youth are randomized to 4 conditions: (1) enhanced standard of care of automated text-messaging and monitoring (AMM) and repeat HIV/STI testing assessment procedures (n=690); (2) online group peer support via private social media plus AMM (n=270); (3) coaching that is strengths-based, youth-centered, unscripted, based on common practice elements of EBI, available over 24 months, and delivered by near-peer paraprofessionals via text, phone, and in-person, plus AMM (n=270); and (4) online group peer support plus coaching and AMM (n=270). RESULTS: The project was funded in September 2016 and enrollment began in May 2017. Enrollment will be completed between June and August 2019. Data analysis is currently underway, and the first results are expected to be submitted for publication in 2019. CONCLUSIONS: This hybrid implementation-effectiveness study examines alternative models for implementing the CDC guidelines for routine HIV/STI testing for YAHR of acquiring HIV and for delivering evidence-based behavioral intervention content in modular elements instead of scripted manuals and available over 24 months of follow-up, while also monitoring implementation, costs, and effectiveness. The greatest impacts are expected for coaching, whereas online group peer support is expected to have lower impact but may be more cost-effective. TRIAL REGISTRATION: ClinicalTrials.gov NCT03134833; https://clinicaltrials.gov/ct2/show/NCT03134833 (Archived by WebCite at http://www.webcitation.org/76el0Viw9). INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/11165.

Acute HIV Infection in Youth: Protocol for the Adolescent Trials Network 147 (ATN147) Comprehensive Adolescent Research and Engagement Studies (CARES) Study.

BACKGROUND: Early treatment studies have shown that prompt treatment of HIV with combination antiretroviral therapy (cART) can limit the size of latent viral reservoirs, thereby providing clinical and public health benefits. Studies have demonstrated that adolescents have a greater capacity for immune reconstitution than adults. Nevertheless, adolescents who acquired HIV through sexual transmission have not been included in early treatment studies because of challenges in identification and adherence to cART. OBJECTIVE: This study aimed to identify and promptly treat with cART youth aged 12 to 24 years in Los Angeles and New Orleans who have acute, recent, or established HIV infection, as determined by Fiebig stages 1 to 6 determined by viral RNA polymerase chain reaction, p24 antigen presence, and HIV-1 antigen Western blot. The protocol recommends treatment on the day of diagnosis when feasible. Surveillance and dedicated behavioral strategies are used to retain them in care and optimize adherence. Through serial follow-up, HIV biomarkers and response to antiretroviral therapy (ART) are assessed. The study aims to assess viral dynamics, decay and persistence of viral reservoirs over time, and correlate these data with the duration of viral suppression. METHODS: A total of 72 youth (36 acutely infected and 36 treatment naïve controls) are enrolled across clinical sites using a current community-based strategy and direct referrals. Youth are prescribed ART according to the standard of care HIV-1 management guidelines and followed for a period of 2 years. Assessments are conducted at specific time points throughout these 2 years of follow-up for monitoring of adherence to ART, viral load, magnitude of HIV reservoirs, and presence of coinfections. RESULTS: The study began enrolling youth in July 2017 across study sites in Los Angeles and New Orleans. As of September 30, 2018, a total of 37 youth were enrolled, 12 with recently acquired, 16 with established HIV infection as determined by Fiebig staging, and 9 pending determination of Fiebig status. Recruitment and enrollment are ongoing. CONCLUSIONS: We hypothesize that the size of the HIV reservoir and immune activation markers will be different across groups treated with cART, that is, those with acute or recent HIV infection and those with established infection. Adolescents treated early who are virally suppressed will have diminished HIV reservoirs than those with established infection. These youth may be potential candidates for a possible HIV vaccine and additional HIV remission intervention trials. Our study will inform future studies of viral remission strategies. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/10807.