Preventing Behavioral Human Immunodeficiency Virus Infections in Adolescents and Young Adults.

HIV prevention in adolescents and young adults (AYA) requires a multi-pronged strategy encompassing behavioral, biologic, and structural approaches. This article reviews the epidemiology of HIV infection in the United States and its pathogenesis and transmission. Prevention approaches are discussed in more detail, with an emphasis on how each approach is relevant to AYA populations. Information is summarized in a resource table with links to references and in-depth discussions of the topics reviewed in this article.

"A Great Way to Start the Conversation": Evidence for the Use of an Adolescent Mental Health Chatbot Navigator for Youth at Risk of HIV and Other STIs.

Chatbot use is increasing for mobile health interventions on sensitive and stigmatized topics like mental health because of their anonymity and privacy. This anonymity provides acceptability to sexual and gendered minority youth (ages 16-24) at increased risk of HIV and other STIs with poor mental health due to higher levels of stigma, discrimination, and social isolation. This study evaluates the usability of Tabatha-YYC, a pilot chatbot navigator created to link these youth to mental health resources. Tabatha-YYC was developed using a Youth Advisory Board (n = 7). The final design underwent user testing (n = 20) through a think-aloud protocol, semi-structured interview, and a brief survey post-exposure which included the Health Information Technology Usability Evaluation Scale. The chatbot was found to be an acceptable mental health navigator by participants. This study provides important design methodology considerations and key insights into chatbot design preferences of youth at risk of STIs seeking mental health resources.

Changes in the time of COVID-19: a quality improvement initiative to maintain services at a youth sexual health clinic.

OBJECTIVES: Adolescents and young adults (AYAs) face difficulties accessing sexual and reproductive health services. These difficulties were exacerbated for a variety of reasons by the COVID-19 pandemic. We document strategies and outcomes implemented at an urban youth sexual health clinic in Florida that allowed uninterrupted provision of services while protecting against spread of COVID-19. METHODS: The plan-do-study-act (PDSA) model was used to implement COVID-19 interventions designed to allow continued service delivery while protecting the health and safety of staff and patients. This method was applied to clinic operations, community referral systems and community outreach to assess and refine interventions within a quick-paced feedback loop. RESULTS: During the COVID-19 pandemic, changes made via PDSA cycles to clinical/navigation services, health communications and youth outreach/engagement effectively responded to AYA needs. Although overall numbers of youth served decreased, all youth contacting the clinic for services were able to be accommodated. Case finding rates for chlamydia, gonorrhoea, syphilis and HIV were similar to pre-pandemic levels. CONCLUSIONS: Quality improvement PDSA initiatives at AYA sexual health clinics, particularly those for underserved youth, can be used to adapt service delivery when normal operating models are disrupted. The ability for youth sexual health clinics to adapt to a changing healthcare landscape will be crucial in ensuring that under-resourced youth are able to receive needed services and ambitious Ending the HIV Epidemic goals are achieved.

HIV self-testing and STI self-collection via mobile apps: experiences from two pilot randomized controlled trials of young men who have sex with men.

BACKGROUND: Young men who have sex with men (YMSM) are disproportionately impacted by HIV and other sexually transmitted infections (STIs) in the United States (US) and have low rates of HIV/STI testing. Provision of HIV self-testing and STI self-collection can increase testing rates, and access to these kits through mobile applications (apps) could help facilitate YMSM using HIV self-testing and STI self-collection. METHODS: Data for this study comes from two pilot randomized controlled trials (RCTs) of mobile apps within the Adolescent Trials Network-LYNX and MyChoices-aimed to increase HIV/STI testing among YMSM (age 15-24) who had not recently tested for HIV and were at high risk for HIV acquisition across five US cities. Both apps include the ability to order a HIV self-test with rapid results and a kit for STI self-collection and mailing of samples for syphilis, gonorrhea and chlamydia to a lab for testing. Using assessments of app users (n=80) at pre-randomization and at 3- and 6-months post-randomization and online interview data from a purposive sample of app users (n=37), we report on experiences and lessons learned with HIV self-testing and STI self-collection kits ordered via the apps. RESULTS: Participants were on average 20.7 years of age (SD =2.4), and 49% were non-White or multiple race/ethnicity. Sixty-three percent had a prior HIV test. Over half (58%) had a prior STI test, but only 3% had tested within the past 3 months. Nearly two-thirds ordered an HIV self-testing kit; of whom, 75% reported using at least one self-test kit over the study period. STI self-collection kit ordering rates were also high (54%); however, STI self-collection kit return rates were lower (13%), but with a high positivity rate (5.3%). Both HIV self-testing and STI self-collection kits were highly acceptable, and 87% reported that it was extremely/very helpful to be able to order these kits through the apps. The most common reason for not ordering the HIV/STI kits was preferring to test at a clinic. In interviews, participants expressed feeling empowered by being able to test at home; however, they also raised concerns around STI sample collection. CONCLUSIONS: HIV self-testing and STI self-collection kit ordering via mobile apps is feasible, acceptable and may show promise in increasing testing rates among YMSM. The LYNX and MyChoices apps are currently being tested in a full-scale efficacy trial, and if successful, these innovative mobile apps could be scaled up to efficiently increase HIV/STI testing among youth across the US.

Scale up mHealth HIV interventions: site and public health perspectives and lessons learned from P3.

A number of mobile health (mHealth) interventions have been shown to be effective and highly acceptable tools for improving human immunodeficiency virus (HIV) prevention and care for youth. Scale-up of efficacious technology-based interventions is challenging and best practices for scale-up have not been clearly established. Developers of mHealth interventions should have plans in mind for wide scale implementation throughout all stages of development including planning, during trials and during analysis and dissemination. We discuss an approach of focus on researchers, funders and potential implementers including members of the community, public health practitioners and policymakers during initial planning, trials, analysis and dissemination, and planning for scale-up. Development of the P3 (Prepared, Protected, emPowered) mobile application (app), an intervention built to encourage and increase pre-exposure prophylaxis (PrEP) adherence among young men who have sex with men (YMSM) and young transgender women who have sex with men (YTWSM), is discussed in terms of designing for scale-up and lessons learned.

Developing a Mobile App (LYNX) to Support Linkage to HIV/Sexually Transmitted Infection Testing and Pre-Exposure Prophylaxis for Young Men Who Have Sex With Men: Protocol for a Randomized Controlled Trial.

BACKGROUND: Young men who have sex with men (YMSM) in the United States have among the highest incidence of HIV and sexually transmitted infection (STI) and the lowest uptake of HIV and STI testing and pre-exposure prophylaxis (PrEP). Nearly universal mobile phone ownership among youth provides an opportunity to leverage mobile health apps to increase HIV/STI testing and PrEP uptake among YMSM. OBJECTIVE: The goals of this project are to develop and refine LYNX, a novel mobile app to support linkage to HIV/STIs testing and PrEP services among YMSM in the United States, and to evaluate the acceptability and feasibility of LYNX in a pilot randomized controlled trial (RCT). METHODS: This research protocol will be conducted in 3 phases: an iterative development phase with a series of 3 focus groups among 20 YMSM to refine the LYNX app; an open technical pilot among 15 YMSM to optimize usability of the app; and then a 6-month pilot RCT among 60 HIV-uninfected YMSM at risk for HIV acquisition. Developed using the Information, Motivation, and Behavioral skills theoretical model, the LYNX app includes an electronic diary to track sexual behaviors (information), a personalized risk score to promote accurate risk perception (information/motivation), testing reminders (motivation/behavioral skills), and access to home-based HIV/STI testing options and geospatial-based HIV/STI testing care sites (behavioral skills). Feasibility and acceptability will be assessed through app analytics of usage patterns and acceptability scales administered via computer-assisted self-interview at 3 and 6 months. We will also evaluate preliminary efficacy by comparing the proportion of YMSM who test at least once during the 6-month pilot and the proportion who successfully link to a PrEP provider in the intervention versus control groups. RESULTS: Formative work is currently underway. The LYNX pilot RCT will begin enrollment in October 2018, with study results available in 2019. CONCLUSIONS: The LYNX app is one of the first mobile apps designed to increase HIV/STI testing and PrEP uptake among YMSM. As low-perceived risk is a barrier to HIV/STI testing and PrEP use among youth, the personalized risk assessment and interactive sexual diary in LYNX could assist YMSM in better understanding their HIV risk and providing motivation to test for HIV/STIs and initiate PrEP. Coupled with community-based recruitment, this novel mobile app has great potential to reach and engage YMSM not currently involved in care and increase rates of HIV/STI testing and PrEP uptake in this vulnerable population. TRIAL REGISTRATION: ClinicalTrials.gov NCT03177512; https://clinicaltrials.gov/ct2/show/NCT03177512 (Archived by WebCite at http://www.webcitation.org/73c917wAw). INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/10659.

Isoniazid for the Prevention of Tuberculosis in HIV-Infected Children: A Systematic Review and Meta-Analysis.

BACKGROUND: Isoniazid is recommended for prevention of tuberculosis (TB) in HIV-infected adults, but its efficacy in children living with HIV (CLHIV) is not known. We performed a systematic review to assess the efficacy of isoniazid for the prevention of TB in CLHIV. METHODS: We searched PubMed, Cochrane Clinical Trial Registry and Google Scholar from inception to December 2016. Any randomized controlled trial assessing the role of isoniazid for the prevention of TB in CLHIV was eligible for inclusion. The primary endpoint was TB incidence; secondary end points were mortality, overall survival and severe adverse events. Dual independent extraction of all data was performed. Data were pooled under a random effects model and summarized either as risk ratio (RR) or hazard ratio along with 95% confidence intervals (CIs). RESULTS: Of 931 references, 3 randomized controlled trials enrolling 977 patients met the inclusion criteria. Pooled results showed a statistically nonsignificant reduction in TB incidence (RR: 0.70; 95% CI: 0.47-1.04; P = 0.07) and mortality (RR: 0.94; 95% CI: 0.39-2.23; P = 0.88) with the use of isoniazid compared with placebo. One study was stopped early because of excess deaths in the placebo arm. However, results from subgroup analysis restricted to only completed trials did not change the overall findings. CONCLUSIONS: Isoniazid did not reduce the incidence of TB in CLHIV. All included studies were performed in regions with high prevalence of TB making the overall generalizability limited.

Medication Adherence in 13- to 24-Year-Old Youth Living With HIV.

Despite advances in HIV medicine, adherence presents as a barrier to effective treatment for youth. We designed this study to assess medication knowledge, adherence, and factors affecting adherence in youth with HIV. Participants were 72 youth ages 13 to 24 years with perinatally or behaviorally acquired HIV. Demographic data were collected and a self-report adherence interview was administered. Interviews were audio-recorded to allow for qualitative data analysis. Self-reported adherence varied depending on the framing of questions, with participants reporting greater adherence when asked how many doses they had missed within the past 7 days compared to results from a 7-day recall interview. At least 74% of the sample said they sometimes forgot to take their medication. A taxonomic approach to the qualitative analysis revealed internal and external facilitators and barriers to adherence. Findings suggest a need for education and provider support to include strategies to improve adherence.

Diagnostic accuracy of self-reported symptomatic assessment versus per speculum/per vaginal examination for the diagnosis of vaginal/cervical discharge and lower abdominal pain syndromes among female sex workers.

BACKGROUND: National AIDS Control Organization guidelines on enhanced syndromic case management of sexually transmitted infections (STIs) and reproductive tract infections (RTIs) require per speculum (P/S) and per vaginal (P/V) examinations for diagnosis of STIs. However, it is not known if the addition of P/S and P/V examinations to self-reported symptomatic assessment adds any value for the diagnosis of STI/RTI. OBJECTIVE: To assess the diagnostic accuracy of P/S and P/V examinations compared with self-reported symptomatic assessment in a cohort of female sex workers (FSWs). METHODS: We performed a cross-sectional study from August 2009 to June 2010, among 519 FSWs in Surat city, Gujarat, India. Symptomatic assessment for the presence or absence of vaginal/cervical discharge (VCD) or lower abdominal pain (LAP) was done using a self-administered questionnaire. After completion of the questionnaire, all participants underwent P/S and P/V examinations. Summary diagnostic accuracy measures were calculated. RESULTS: Five hundred and nineteen FSWs between the ages of 18-49 years participated in the study. The median age of participants was 31 years. The prevalence of VCD and LAP syndromes based on vaginal discharge, LAP, or both was 56%, 5,-10%, respectively. The sensitivity of P/S and P/V examinations depending on symptomatic assessment ranged from 47% to 76%. The specificity ranged from 73% to 93%. The positive predictive value ranged from 25% to 83%, and the negative predictive value ranged from 56% to 98%. CONCLUSION: Symptomatic assessment alone is not adequate for the diagnosis of VCD and LAP syndromes and can lead to a significant number of missed cases (36%). A P/S and P/V examinations is critical for assessment of VCD and LAP syndromes and subsequent treatment.

Immune Reconstitution but Persistent Activation After 48 Weeks of Antiretroviral Therapy in Youth With Pre-Therapy CD4 >350 in ATN 061.

BACKGROUND: Measures of immune outcomes in youth who initiate combination antiretroviral therapy (cART) early in HIV infection are limited. DESIGN: Adolescent Trials Network 061 examined changes over 48 weeks of cART in T-cell subsets and markers of T-cell and macrophage activation in subjects with pre-therapy CD4 > 350 cells/mm. All subjects had optimal viral suppression from weeks 24 through 48. METHODS: Subjects (n = 48) initiated cART with tenofovir/emtricitabine plus ritonavir-boosted atazanavir. Data were collected at baseline and weeks 12, 24, and 48. Trends were compared to uninfected controls. RESULTS: Significant increases over 48 weeks were noted in all CD4 populations, including total, naive, central memory (CM), and effector memory RO (EM RO) and effector memory RA (EM RA), whereas numbers of CM and EM RO CD8 cells declined significantly. By week 48, CD4 naive cells were similar to controls, whereas CM CD4 cells remained significantly lower and EM RO and EM RA subsets were significantly higher. CD38 and HLA DR expression, both individually and when co-expressed, decreased over 48 weeks of cART on CD8 cells but remained significantly higher than controls at week 48. In contrast, markers of macrophage activation measured by sCD14 and sCD163 in plasma did not change with cART and were significantly higher than controls. CONCLUSIONS: In youth initiating early cART, CD4 cell reconstitution is robust with decreases in CD8 cells. However, CD8 T-cell and macrophage activation persists at higher levels than uninfected controls.

Growth Patterns of HIV Infected Indian Children in Response to ART: A Clinic Based Cohort Study.

OBJECTIVE: To describe catch-up growth after antiretroviral therapy (ART) initiation among children living with human immunodeficiency virus (CLHIV), attending a private clinic in India. METHODS: This is a retrospective analysis of data of CLHIV attending Prayas clinic, Pune, India. Height and weight z scores (HAZ, WAZ) were calculated using WHO growth charts. Catch-up growth post-ART was assessed using a mixed method model in cases where baseline and at least one subsequent follow-up HAZ/WAZ were available. STATA 12 was used for statistical analysis. RESULTS: During 1998 to 2011, 466 children were enrolled (201 girls and 265 boys; median age = 7 y). A total of 302 children were ever started on ART; of which 73 and 76 children were included for analysis for catch up growth in WAZ and HAZ respectively. Median WAZ and HAZ increased from -2.14 to -1.34 (p = 0.007) and -2.42 to -1.94 (p = 0.34), respectively, 3 y post ART. Multivariable analysis using mixed model (adjusted for gender, guardianship, baseline age, baseline WAZ/HAZ, baseline and time varying WHO clinical stage) showed gains in WAZ (coef = 0.2, 95 % CI: -0.06 to 0.46) and HAZ (coef = 0.49, 95 % CI: 0.21 to 0.77) with time on ART. Lower baseline WAZ/HAZ and older age were associated with impaired catch-up growth. Children staying in institutions and with baseline advanced clinical stage showed higher gain in WAZ. CONCLUSIONS: The prevalence of stunting and underweight was high at ART initiation. Sustained catch-up growth was seen with ART. The study highlights the benefit of early ART in achieving normal growth in CLHIV.

Decisional capacity and medication adherence among youth with HIV.

This exploratory study examined the degree to which decisional capacity (DC) is associated with measures of self-reported medication adherence. We hypothesized that youth with higher levels of DC would report greater levels of antiretroviral medication adherence. Seventy-two (72) youth with HIV aged 13-24 participated in this study. Data collection included administration of the MacArthur Competence Tool for Treatment and measures of adherence (i.e., seven-day self-report interview, visual analog scale, and biological indicators). Data were analyzed using descriptive statistics, intercorrelations, and multiple and Poisson regression analyses. Youth with HIV who exhibited greater understanding of their disease were more likely to report fewer missed doses in the last seven days. Findings build upon literature in the areas of DC and health literacy and highlight the potential utility of enhancing HIV disease understanding among youth with HIV.

Decisional capacity among youth with HIV: results from the MacArthur Competence Tool for Treatment.

We assessed the decisional capacity (DC) of 72 youth with HIV, ages 13-24, using the MacArthur Competence Tool for Treatment, a structured interview that assesses DC along the following dimensions: understanding, appreciation, reasoning, and the ability to express a choice. Using previously established cutoff scores, results suggested 100% of youth were competent in the area of appreciation, but only 62% and 60% were competent in the areas of understanding and reasoning, respectively. Additional descriptive analyses reveal more detailed information regarding specific strengths and weaknesses within each of the dimensions of decisional capacity. These findings have important implications for health literacy initiatives, medical education, and treatment for youth with HIV, and support the need for adherence and secondary prevention interventions that include a decisional capacity component.

Primary care guidelines for the management of persons infected with HIV: 2013 update by the HIV medicine association of the Infectious Diseases Society of America.

Evidence-based guidelines for the management of persons infected with human immunodeficiency virus (HIV) were prepared by an expert panel of the HIV Medicine Association of the Infectious Diseases Society of America. These updated guidelines replace those published in 2009. The guidelines are intended for use by healthcare providers who care for HIV-infected patients. Since 2009, new antiretroviral drugs and classes have become available, and the prognosis of persons with HIV infection continues to improve. However, with fewer complications and increased survival, HIV-infected persons are increasingly developing common health problems that also affect the general population. Some of these conditions may be related to HIV infection itself or its treatment. HIV-infected persons should be managed and monitored for all relevant age- and sex-specific health problems. New information based on publications from the period 2009-2013 has been incorporated into this document.

Primary care guidelines for the management of persons infected with HIV: 2013 update by the HIV Medicine Association of the Infectious Diseases Society of America.

Evidence-based guidelines for the management of persons infected with human immunodeficiency virus (HIV) were prepared by an expert panel of the HIV Medicine Association of the Infectious Diseases Society of America. These updated guidelines replace those published in 2009. The guidelines are intended for use by healthcare providers who care for HIV-infected patients. Since 2009, new antiretroviral drugs and classes have become available, and the prognosis of persons with HIV infection continues to improve. However, with fewer complications and increased survival, HIV-infected persons are increasingly developing common health problems that also affect the general population. Some of these conditions may be related to HIV infection itself or its treatment. HIV-infected persons should be managed and monitored for all relevant age- and sex-specific health problems. New information based on publications from the period 2009-2013 has been incorporated into this document.

Murine typhus as a cause of cognitive impairment: case report and a review of the literature.

BACKGROUND: Murine typhus is a systemic febrile illness caused by Rickettsia typhi, a gram-negative, obligate intracellular bacterium. It is found worldwide, including in the United States, where cases are concentrated in suburban areas of Texas and California. The disease manifests with fever, headache, and rash. Central nervous system involvement is rare in both adults and children. Aseptic meningitis and meningoencephalitis are the most common neurological presentations, occurring in 2% to 5% of cases. Neurological dysfunction, including memory impairment and behavioral alterations, can occur and usually are reversible. Long-term deficits are considered rare even in untreated cases and have not been described in the pediatric population. METHODS: Single case report. RESULTS: We describe a previously healthy 17-year-old girl infected with R. typhi who developed meningoencephalitis that resulted in chronic cognitive impairment despite treatment. CONCLUSION: Murine typhus should be considered in the differential diagnosis of aseptic meningitis and meningoencephalitis. Early diagnosis and treatment can prevent death and long-term morbidity.

Incidence of opportunistic illness before and after initiation of highly active antiretroviral therapy in children.

BACKGROUND: Little is known about immune reconstitution inflammatory syndrome in children in the United States. METHODS: LEGACY is a longitudinal cohort study of HIV-infected participants 0-24 years at enrollment during 2005 to 2007 from 22 US clinics. For this analysis, we included participants with complete medical record abstraction from birth or time of HIV diagnosis through 2006. Opportunistic illness (OI) included AIDS-defining conditions and selected HIV-related diagnoses. We calculated the incidence (#/100 patient-years) of OI diagnosed in the months pre- and postinitiation of the first highly active antiretroviral therapy (HAART) regimen which was followed by ≥1 log reduction in HIV viral load. We defined OI as immune reconstitution inflammatory syndrome if an OI incidence increased after HAART initiation. "Responders" were defined as experiencing ≥1 log decline in viral load within 6 months after HAART initiation. RESULTS: Among 575 patients with complete chart abstraction, 524 received HAART. Of these 524 patients, 343 were responders, 181 were nonresponders and 86 experienced OI. Responders accounted for 98 of 124 (79%) of OI. Pre-HAART and post-HAART OI incidences were 43.7 and 24.4 (P = 0.003), respectively, among responders and 15.9 and 9.1 (P = 0.2), respectively, among nonresponders. Overall, OI incidences among responders and nonresponders were 33.8 and 12.3, respectively (P = 0.002). Responders were more likely than nonresponders to experience herpes simplex and herpes zoster before HAART initiation (all, P < 0.002). CONCLUSIONS: The lack of immune reconstitution inflammatory syndrome in participants initiating HAART may be due to low overall OI rates. The unexpectedly higher OI prevalence comprised mainly of herpes simplex and zoster, before HAART initiation among responders, may have motivated them to better adhere to HAART.