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.

CLINICALTRIAL

ClinicalTrials.gov NCT03109431; https://clinicaltrials.gov/ct2/show/NCT03109431

INTERNATIONAL REGISTERED REPOR

DERR1-10.2196/10791

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.

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.

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.

CLINICALTRIAL

ClinicalTrials.gov NCT03134833; https://clinicaltrials.gov/ct2/show/NCT03134833 (Archived by WebCite at http://www.webcitation.org/76el0Viw9)

INTERNATIONAL REGISTERED REPOR

DERR1-10.2196/11165

Background

Over 20% of HIV diagnoses in the United States are among youth aged 12-24 years. Furthermore, youth have the lowest rates of uptake and adherence to antiretroviral (ARV) medications and are least aware of their HIV status.

Objective

Our objective was to design a set of interrelated studies to promote completion of each step of the HIV Prevention Continuum by uninfected youth at high risk (YHR), as well as completion of steps in the Treatment Continuum by youth living with HIV (YLH).

Methods

Gay, bisexual, and transgender youth; homeless youth; substance-abusing youth; youth with criminal justice contact; and youth with significant mental health challenges, particularly black and Latino individuals, are being recruited from 13 community-based organizations, clinics, drop-in centers, and shelters in Los Angeles and New Orleans. Youth are screened on the basis of self-reports and rapid diagnostic tests for HIV, drug use, and sexually transmitted infections and, then, triaged into one of 3 studies: (1) an observational cohort of YLH who have never received ARV medications and are then treated-half initially are in the acute infection period (n=36) and half with established HIV infection (n=36); (2) a randomized controlled trial (RCT) for YLH (N=220); and (3) an RCT for YHR (N=1340). Each study contrasts efficacy and costs of 3 interventions: an automated messaging and weekly monitoring program delivered via text messages (short message service, SMS); a peer support intervention delivered via social media forums; and coaching, delivered via text message (SMS), phone, and in-person or telehealth contacts. The primary outcomes are assessing youths' uptake and retention of and adherence to the HIV Prevention or Treatment Continua. Repeat assessments are conducted every 4 months over 24 months to engage and retain youth and to monitor their status.

Results

The project is funded from September 2016 through May 2021. Recruitment began in May 2017 and is expected to be completed by June 2019. We expect to submit the first results for publication by fall 2019.

Conclusions

Using similar, flexible, and adaptable intervention approaches for YLH and YHR, this set of studies may provide a roadmap for communities to broadly address HIV risk among youth. We will evaluate whether the interventions are cost-efficient strategies that can be leveraged to help youth adhere to the actions in the HIV Prevention and Treatment Continua.

International registered report identifier (irrid)

DERR1-10.2196/10759.

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.

BACKGROUND

Over 20% of HIV diagnoses in the United States are among youth aged 12-24 years. Furthermore, youth have the lowest rates of uptake and adherence to antiretroviral (ARV) medications and are least aware of their HIV status.

OBJECTIVE

Our objective was to design a set of interrelated studies to promote completion of each step of the HIV Prevention Continuum by uninfected youth at high risk (YHR), as well as completion of steps in the Treatment Continuum by youth living with HIV (YLH).

METHODS

Gay, bisexual, and transgender youth; homeless youth; substance-abusing youth; youth with criminal justice contact; and youth with significant mental health challenges, particularly black and Latino individuals, are being recruited from 13 community-based organizations, clinics, drop-in centers, and shelters in Los Angeles and New Orleans. Youth are screened on the basis of self-reports and rapid diagnostic tests for HIV, drug use, and sexually transmitted infections and, then, triaged into one of 3 studies: (1) an observational cohort of YLH who have never received ARV medications and are then treated—half initially are in the acute infection period (n=36) and half with established HIV infection (n=36); (2) a randomized controlled trial (RCT) for YLH (N=220); and (3) an RCT for YHR (N=1340). Each study contrasts efficacy and costs of 3 interventions: an automated messaging and weekly monitoring program delivered via text messages (short message service, SMS); a peer support intervention delivered via social media forums; and coaching, delivered via text message (SMS), phone, and in-person or telehealth contacts. The primary outcomes are assessing youths’ uptake and retention of and adherence to the HIV Prevention or Treatment Continua. Repeat assessments are conducted every 4 months over 24 months to engage and retain youth and to monitor their status.

RESULTS

The project is funded from September 2016 through May 2021. Recruitment began in May 2017 and is expected to be completed by June 2019. We expect to submit the first results for publication by fall 2019.

CONCLUSIONS

Using similar, flexible, and adaptable intervention approaches for YLH and YHR, this set of studies may provide a roadmap for communities to broadly address HIV risk among youth. We will evaluate whether the interventions are cost-efficient strategies that can be leveraged to help youth adhere to the actions in the HIV Prevention and Treatment Continua.

INTERNATIONAL REGISTERED REPOR

DERR1-10.2196/10759

Background

Tenofovir disoproxil fumarate (TDF) decreases bone mineral density (BMD). We hypothesized that vitamin D3 (VITD3) would increase BMD in youth receiving TDF.

Methods

This was a randomized, double-blind, placebo-controlled trial of directly observed VITD3 vs placebo every 4 weeks for 48 weeks in youth aged 16-24 years with HIV, RNA load <200 copies/mL, taking TDF-containing combination antiretroviral therapy (TDF-cART) for ≥180 days. Participants (N = 214) received a daily multivitamin containing VITD3 400 IU and calcium 162 mg, plus monthly randomized VITD3 50000 IU (n = 109) or placebo (n = 105). Outcome was change from baseline to week 48 in lumbar spine BMD (LSBMD). Data presented are median (Q1, Q3).

Results

Participants were aged 22.0 (21.0, 23.0) years, 84% were male, and 74% were black/African American. At baseline, 62% had 25-hydroxy vitamin D (25-OHD) <20 ng/mL. Multivitamin adherence was 49% (29%, 69%), and VITD3/placebo adherence 100% (100%, 100%). Vitamin D intake was 2020 (1914, 2168) and 284 (179, 394) IU/day, and serum 25-OHD concentration was 36.9 (30.5, 42.4) and 20.6 (14.4, 25.8) ng/mL at 48 weeks in VITD3 and placebo groups, respectively (P < .001). From baseline to week 48, LSBMD increased by 1.15% (-0.75% to 2.74%) in the VITD3 group (n = 99; P < .001) and 0.09% (-1.49% to 2.61%) in the placebo group (n = 89; P = .25), without between-group difference (P = .12). VITD3 group changes occurred with baseline 25-OHD <20 ng/mL (1.17% [-.82% to 2.90%]; P = .004) and ≥20 ng/mL (0.93% [-.26% to 2.15%]; P = .033).

Conclusions

For youth taking TDF-cART, LSBMD increased through 48 weeks with VITD3 plus multivitamin, but not with placebo plus multivitamin, independent of baseline vitamin D status.

Clinical trials registration

NCT01751646.