Peers plus mobile app for treatment in HIV (PATH): protocol for a randomized controlled trial to test a community-based integrated peer support and mHealth intervention to improve viral suppression among Hispanic and Black people living with HIV.

BACKGROUND: Significant disparities continue to exist in the HIV care continuum, whereby Hispanic and Black people living with HIV (PLWH) are less likely to achieve viral suppression compared to their White counterparts. Studies have shown that intervention approaches that involve peer navigation may play an important role in supporting patients to stay engaged in HIV care. However, implementation may be challenging in real-world settings where there are limited resources to support peer navigators. Combining a peer navigation approach with scalable mobile health (mHealth) technology may improve impact and implementation outcomes. METHODS: We combined a peer navigation intervention with a mHealth application and are conducting a randomized controlled trial (RCT) to test the efficacy of this integrated "Peers plus mobile App for Treatment in HIV" (PATH) intervention to improve HIV care engagement, and ultimately sustained viral suppression, among Hispanic and Black PLWH. We will enroll up to 375 PLWH into a two-arm prospective RCT, conducting follow-up assessments every 3 months up to 12 months post-baseline. Participants randomized to the control arm will continue to receive usual care Ryan White Program case management services. Individuals randomized to receive the PATH intervention will receive usual care plus access to two main intervention components: (1) a peer navigation program and (2) a mHealth web application. The primary outcome is sustained HIV viral suppression (undetectable viral load observed at 6- and 12-month follow-up). Secondary outcomes are retention in HIV care, gaps in HIV medical visits, and self-reported ART adherence. Recruitment for the RCT began in November 2021 and will continue until June 2024. Follow-up assessments and medical chart abstractions will be conducted to collect measurements of outcome variables. DISCUSSION: The efficacy trial of PATH will help to fill gaps in our scientific understanding of how a combined peer navigation and mHealth approach may produce effects on HIV care outcomes while addressing potential implementation challenges of peer navigation in Ryan White-funded clinics. TRIAL REGISTRATION: The PATH trial is registered at the United States National Institutes of Health National Library of Medicine (ClinicalTrials.gov) under ID # NCT05427318 . Registered on 22 June 2022.

Scaling and sustaining COVID-19 vaccination through meaningful community engagement and care coordination for underserved communities: hybrid type 3 effectiveness-implementation sequential multiple assignment randomized trial.

BACKGROUND: COVID-19 inequities are abundant in low-income communities of color. Addressing COVID-19 vaccine hesitancy to promote equitable and sustained vaccination for underserved communities requires a multi-level, scalable, and sustainable approach. It is also essential that efforts acknowledge the broader healthcare needs of these communities including engagement in preventive services. METHODS: This is a hybrid type 3 effectiveness-implementation study that will include a multi-level, longitudinal, mixed-methods data collection approach designed to assess the sustained impact of a co-created multicomponent strategy relying on bidirectional learning, shared decision-making, and expertise by all team members. The study capitalizes on a combination of implementation strategies including mHealth outreach with culturally appropriate messaging, care coordination to increase engagement in high priority preventive services, and the co-design of these strategies using community advisory boards led by Community Weavers. Community Weavers are individuals with lived experience as members of an underserved community serving as cultural brokers between communities, public health systems, and researchers to co-create community-driven, culturally sensitive public health solutions. The study will use an adaptive implementation approach operationalized in a sequential multiple assignment randomized trial design of 300 participants from three sites in a Federally Qualified Health Center in Southern California. This design will allow examining the impact of various implementation strategy components and deliver more intensive support to those who benefit from it most. The primary effectiveness outcomes are COVID-19 vaccine completion, engagement in preventive services, and vaccine confidence. The primary implementation outcomes are reach, adoption, implementation, and maintenance of the multicomponent strategy over a 12-month follow-up period. Mixed-effects logistic regression models will be used to examine program impacts and will be triangulated with qualitative data from participants and implementers. DISCUSSION: This study capitalizes on community engagement, implementation science, health equity and communication, infectious disease, and public health perspectives to co-create a multicomponent strategy to promote the uptake of COVID-19 vaccination and preventive services for underserved communities in San Diego. The study design emphasizes broad engagement of our community and clinic partners leading to culturally sensitive and acceptable strategies to produce lasting and sustainable increases in vaccine equity and preventive services engagement. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05841810 May 3, 2023.

Proyecto Compadre: Using Implementation Science to Tailor Peer Navigation for Latino Men in the US-Mexico Border Region.

BACKGROUND: Latino men who have sex with men (MSM) in San Diego have poor HIV testing and prevention outcomes compared with non-Latino White men. Peer navigation (PN) is a promising evidence-based intervention to reduce disparities but needs tailoring for Latino MSM. SETTINGS: Health centers near the US-Mexico border. METHODS: Using the Exploration, Preparation, Implementation, Sustainment Framework, we conducted mixed-methods implementation science study. In phase I, we conducted interviews with Latino men (n = 15), focus groups with staff (n = 7), and surveys with all to understand the Exploration, Preparation, Implementation, Sustainment factors associated with HIV testing and care linkage. In phase II, we conducted 31 web-based surveys with Latino men and staff to rank intervention and implementation strategies from phase I. Quantitative data were analyzed descriptively, integrated with qualitative data, and reviewed by our community-academic partnership to develop an implementation model. RESULTS: Latino men (N = 15) were 94% Spanish speaking, 67% gay identified, 27% US born, and their suggestions were to have navigators use peer referral to address barriers such as stigma; use the Latino social network to expand reach, leverage social media for peer-led intervention, and disseminate HIV information. Staff (N = 26) were 77% Spanish speaking, 35% gay-identified, 96% trained in cultural competency, and suggested including culturally appropriate HIV educational materials in Spanish, status and identity neutral programs, administrative/supervisorial/training structure for PNs, and PN compensation and team integration. Overall, results emphasized a need for a formalized PN model centered on referrals and using existing Latino community social networks. CONCLUSIONS: Findings can be packaged for future implementation of PN programs for Latino MSM.

MRI Assessment of Treatment Response in HIV-associated NAFLD: A Randomized Trial of a Stearoyl-Coenzyme-A-Desaturase-1 Inhibitor (ARRIVE Trial).

Aramchol, an oral stearoyl-coenzyme-A-desaturase-1 inhibitor, has been shown to reduce hepatic fat content in patients with primary nonalcoholic fatty liver disease (NAFLD); however, its effect in patients with human immunodeficiency virus (HIV)-associated NAFLD is unknown. The aramchol for HIV-associated NAFLD and lipodystrophy (ARRIVE) trial was a double-blind, randomized, investigator-initiated, placebo-controlled trial to test the efficacy of 12 weeks of treatment with aramchol versus placebo in HIV-associated NAFLD. Fifty patients with HIV-associated NAFLD, defined by magnetic resonance imaging (MRI)-proton density fat fraction (PDFF) ≥5%, were randomized to receive either aramchol 600 mg daily (n = 25) or placebo (n = 25) for 12 weeks. The primary endpoint was a change in hepatic fat as measured by MRI-PDFF in colocalized regions of interest. Secondary endpoints included changes in liver stiffness using magnetic resonance elastography (MRE) and vibration-controlled transient elastography (VCTE), and exploratory endpoints included changes in total-body fat and muscle depots on dual-energy X-ray absorptiometry (DXA), whole-body MRI, and cardiac MRI. The mean (± standard deviation) of age and body mass index were 48.2 ± 10.3 years and 30.7 ± 4.6 kg/m2 , respectively. There was no difference in the reduction in mean MRI-PDFF between the aramchol group at -1.3% (baseline MRI-PDFF 15.6% versus end-of-treatment MRI-PDFF 14.4%, P = 0.24) and the placebo group at -1.4% (baseline MRI-PDFF 13.3% versus end-of-treatment MRI-PDFF 11.9%, P = 0.26). There was no difference in the relative decline in mean MRI-PDFF between the aramchol and placebo groups (6.8% versus 1.1%, P = 0.68). There were no differences in MRE-derived and VCTE-derived liver stiffness and whole-body (fat and muscle) composition analysis by MRI or DXA. Compared to baseline, end-of-treatment aminotransferases were lower in the aramchol group but not in the placebo arm. There were no significant adverse events. Conclusion: Aramchol, over a 12-week period, did not reduce hepatic fat or change body fat and muscle composition by using MRI-based assessment in patients with HIV-associated NAFLD (clinicaltrials.gov ID:NCT02684591).

Randomized Trial of a Health Coaching Intervention to Enhance Retention in Care: California Collaborative Treatment Group 594.

Poor linkage, engagement and retention remain significant barriers in achieving HIV treatment goals in the US. HIV-infected persons entering or re-entering care across three Southern California academic HIV clinics, were randomized (1:1) to an Active, Linkage, Engagement, Retention and Treatment (ALERT) specialist for outreach and health coaching, or standard of care (SOC). The primary outcome of time to loss to follow up (LTFU) was compared using Cox proportional hazards regression modeling. No differences in the median time to LTFU (81.7 for ALERT versus 93.6 weeks for SOC; HR 1.27; p = 0.40), or time to ART initiation was observed (N = 116). Although, ALERT participants demonstrated worsening depressive symptomatology from baseline to week 48 compared to SOC (p = 0.02). The ALERT intervention did not improve engagement and retention in HIV care over SOC. Further studies are needed to determine how best to apply resources to improve retention and engagement.

Characterizing HIV transmission networks across the United States.

BACKGROUND: Clinically, human immunodeficiency virus type 1 (HIV-1) pol sequences are used to evaluate for drug resistance. These data can also be used to evaluate transmission networks and help describe factors associated with transmission risk. METHODS: HIV-1 pol sequences from participants at 5 sites in the CFAR Network of Integrated Clinical Systems (CNICS) cohort from 2000-2009 were analyzed for genetic relatedness. Only the first available sequence per participant was included. Inferred transmission networks ("clusters") were defined as ≥2 sequences with ≤1.5% genetic distance. Clusters including ≥3 patients ("networks") were evaluated for clinical and demographic associations. RESULTS: Of 3697 sequences, 24% fell into inferred clusters: 155 clusters of 2 individuals ("dyads"), 54 clusters that included 3-14 individuals ("networks"), and 1 large cluster that included 336 individuals across all study sites. In multivariable analyses, factors associated with being in a cluster included not using antiretroviral (ARV) drugs at time of sampling (P < .001), sequence collected after 2004 (P < .001), CD4 cell count >350 cells/mL (P < .01), and viral load 10,000-100,000 copies/mL (P < .001) or >100,000 copies/mL (P < .001). In networks, women were more likely to cluster with other women (P < .001), and African Americans with other African Americans (P < .001). CONCLUSIONS: Molecular epidemiology can be applied to study HIV transmission networks in geographically and demographically diverse cohorts. Clustering was associated with lack of ARV use and higher viral load, implying transmission may be interrupted by earlier diagnosis and treatment. Observed female and African American networks reinforce the importance of diagnosis and prevention efforts targeted by sex and race.

Transmitted drug resistance in the CFAR network of integrated clinical systems cohort: prevalence and effects on pre-therapy CD4 and viral load.

Human immunodeficiency virus type 1 (HIV-1) genomes often carry one or more mutations associated with drug resistance upon transmission into a therapy-naïve individual. We assessed the prevalence and clinical significance of transmitted drug resistance (TDR) in chronically-infected therapy-naïve patients enrolled in a multi-center cohort in North America. Pre-therapy clinical significance was quantified by plasma viral load (pVL) and CD4+ cell count (CD4) at baseline. Naïve bulk sequences of HIV-1 protease and reverse transcriptase (RT) were screened for resistance mutations as defined by the World Health Organization surveillance list. The overall prevalence of TDR was 14.2%. We used a Bayesian network to identify co-transmission of TDR mutations in clusters associated with specific drugs or drug classes. Aggregate effects of mutations by drug class were estimated by fitting linear models of pVL and CD4 on weighted sums over TDR mutations according to the Stanford HIV Database algorithm. Transmitted resistance to both classes of reverse transcriptase inhibitors was significantly associated with lower CD4, but had opposing effects on pVL. In contrast, position-specific analyses of TDR mutations revealed substantial effects on CD4 and pVL at several residue positions that were being masked in the aggregate analyses, and significant interaction effects as well. Residue positions in RT with predominant effects on CD4 or pVL (D67 and M184) were re-evaluated in causal models using an inverse probability-weighting scheme to address the problem of confounding by other mutations and demographic or risk factors. We found that causal effect estimates of mutations M184V/I (-1.7 log10pVL) and D67N/G (-2.1[³âˆšCD4] and 0.4 log10pVL) were compensated by K103N/S and K219Q/E/N/R. As TDR becomes an increasing dilemma in this modern era of highly-active antiretroviral therapy, these results have immediate significance for the clinical management of HIV-1 infections and our understanding of the ongoing adaptation of HIV-1 to human populations.

Defining treatment failure in resource-rich settings.

PURPOSE OF REVIEW: To define treatment failure in resource-rich settings; summarizing current guidelines, assays, the significance of detectable viremia, and definitions of treatment failure in clinical and research settings. RECENT FINDINGS: The goal of treatment should be full viral suppression, even in highly treatment-experienced patients. SUMMARY: Treatment failure is defined as repeated HIV RNA values above the lower limit of detection of a sensitive assay (usually 50 copies/ml). This criterion is based on evidence that the maximum clinical benefit of antiretroviral therapy is derived by keeping the viral load as low as possible. Full viral suppression should be achievable in all patients, both treatment-naïve and experienced. Transient, low-detectable viremia ('blips') may not predict virologic breakthrough. However, consecutive or higher-level transient viremia is associated with risk of treatment failure. Defining failure by a confirmed HIV RNA more than 50 copies/ml is the most conservative approach, but the use of such low limits of detection in clinical trials may lead to a high false-positive 'failure' rate, thus a definition of 200 copies/ml may be preferable. Variation in clinical trial endpoint definitions creates a challenge for comparing results between studies. For example, using a composite endpoint to define treatment failure may result in a high proportion of 'failures' that are not related to poor virologic response.