Augmentation Samplers for Multinomial Probit Bayesian Additive Regression Trees.

The multinomial probit (MNP) (Imai and van Dyk, 2005) framework is based on a multivariate Gaussian latent structure, allowing for natural extensions to multilevel modeling. Unlike multinomial logistic models, MNP does not assume independent alternatives. Kindo et al.

HIV drug resistance in children and adolescents on NNRTI-based antiretroviral therapy and subsequent virologic response to dolutegravir-based regimens in Ghana.

HIV drug resistance (HIVDR) was retrospectively characterized among 20 children and adolescents with HIV with virologic failure on non-nucleoside reverse transcriptase inhibitor (NNRTI)-based therapy, and virologic response in those switched to dolutegravir (DTG)-based therapy described. All participants had at least one NNRTI resistance mutation, most commonly K103N (N = 12) and 15 (75%) had nucleoside reverse transcriptase inhibitor (NRTI) resistance mutations, most commonly M184I/V (N = 15). Five (45%) of 11 participants who were switched to DTG-based regimens for a median of 50 months had HIV suppression.

Integrating Partner Services and Molecular Epidemiology Data to Enhance HIV Transmission Disruption in Rhode Island.

Objectives: Evaluate added value of integrating partner services and molecular epidemiology data to disrupt HIV transmission.

Design: Integration of statewide partner services and molecular databases.

Methods: We evaluated overlap of persons and their social/molecular links in contact tracing (Contact Tracing Database [CTDB], 2008-2022) and HIV-1 genomic (Genomic Database [GDB], 2004-2023) databases using Jaccard coefficient (JC); inferred molecular clustering using phylogeny; assessed care engagement gaps by developing a "partner naming" cascade; and explored associations of molecular clustering and partner naming using generalized estimating equations.

Evaluation of antiretroviral regimen switching options in adults with HIV with sustained viral load non-suppression on dolutegravir, lamivudine, and tenofovir in eastern, central, southern, and western Africa: a modelling study.

Background: In Africa, for people with HIV on a dolutegravir-based regimen with a viral load of more than 1000 copies per mL despite enhanced adherence counselling, the appropriate course of action is uncertain. We aimed to evaluate the predicted effects of alternative antiretroviral regimen switching options in this population, including consideration of cost-effectiveness.

Methods: We used an existing individual-based model to simulate risk and experience of HIV in 100 000 adults alive between 1989 and 2076.

Lenacapavir-associated drug resistance: implications for scaling up long-acting HIV pre-exposure prophylaxis.

Although drug resistance could emerge if lenacapavir is initiated during undiagnosed acute infection or if infection occurs during the drug's pharmacokinetic tail, these cases will not compromise the effectiveness of WHO-recommended therapies, as there is no cross-resistance between lenacapavir and other licensed antiretroviral drugs. Lenacapavir pre-exposure prophylaxis (PrEP) is also unlikely to drive population-level lenacapavir resistance given the rarity of breakthrough infections and the reduced replication capacity of most lenacapavir-resistant variants, which most likely reduces their transmission potential. Conversely, the risk of acquiring lenacapavir-resistant HIV-1 while receiving lenacapavir PrEP is likely to remain extremely low, as lenacapavir-associated drug-resistance mutations are rare among individuals without previous lenacapavir exposure, and widespread use of lenacapavir-based regimens remains years away.

Do we need routine integrase resistance testing before starting antiretroviral therapy?

Oral second-generation integrase strand transfer inhibitors are now anchor drugs of antiretroviral therapy (ART) globally due to their high resistance barriers. In high-income settings, guidelines recommend routine protease and reverse transcriptase resistance testing before ART initiation but suggest routine integrase resistance testing only for individuals at elevated risk of integrase resistance. Improved characterisation of transmitted integrase resistance, its detection, and its clinical impact will guide future recommendations for clinical decision making.

Initial and Subsequent Engagement of Recently Diagnosed Persons Living with HIV in Contact Tracing Interviews Conducted by Public Health Practitioners.

Contact tracing is effective in disrupting HIV transmission, but may be limited by the reluctance or inability of recently HIV-diagnosed persons (RDPs) to engage collaboratively with public health. Leveraging an ongoing study endeavoring to increase the yield of standard-of-care contact tracing by re-interviewing a subset of RDPs, we assessed RDP engagement during first and second interviews and compared the two. We used Likert scale scores to develop and employ a 35-point index tool, to assess engagement during first interviews (standard of care) and second interviews (executed in a parent study to inform RDPs of clustering in an attempt to identify additional contacts).

Newly Diagnosed Individuals in Molecular HIV-1 Clusters in Rhode Island over Three Decades.

Background: Characterizing clustering rates of people with HIV in high-risk populations can offer insights on the HIV epidemic, enhancing efforts to control its spread.

Methods: We investigated longitudinal dynamics of clustering rates among individuals newly diagnosed with HIV-1. Data were extracted from medical records of all people with HIV in Rhode Island with available viral sequences.

HIV drug resistance, early treatment outcomes and impact of guidelines compliance after protease inhibitor-based second-line failure in a dedicated resistance clinic in western Kenya: a retrospective cohort study.

Introduction: Data on drug resistance, viral outcomes and guidelines compliance following protease inhibitor (PI)-based second-line failure in low- and middle-income countries are limited, particularly in the era of dolutegravir-containing antiretroviral therapy (ART).

Methods: We conducted a retrospective cohort study of people living with HIV (PLWH) ≥3 years old with second-line viral failure (VF, ≥1000 copies/ml) at the Academic Model Providing Access to Healthcare from 2011 to 2021. We assessed resistance prevalence and patterns at second-line VF, stratified by PI (atazanavir/ritonavir or lopinavir/ritonavir), and examined correlations of resistance and treatment strategies with VF at 6-18 months post-genotype.

Risks and benefits of engaging youth living with HIV in research: perspectives from Kenyan Youth, caregivers, and subject matter experts.

Background: Involving children and adolescents (youth) living with HIV (YLWH) in research is critical for developing appropriate HIV care services and interventions. However, this vulnerable population may not adequately weigh risks against benefits when participating in research, forming an ethical concern, yet little is known about how YLWH perceive these risks and benefits. To inform research-related policies and procedures, we sought perspectives of Kenyan YLWH, their caregivers and subject matter experts (SMEs) on risks and benefits of participation in research in a setting with a high burden of youth HIV infection.

Treatment of Advanced HIV in the Modern Era.

Antiretroviral therapy has transformed human immunodeficiency virus (HIV) infection from a fatal illness into a manageable chronic condition. However, despite remarkable progress, the HIV epidemic remains a global health challenge, with ambitious targets such as 95-95-95 by 2030 at risk of being unmet. While antiretroviral therapy availability has expanded worldwide, gaps persist, including unawareness of HIV status, inconsistent medication uptake, and limited engagement in care across diverse settings.

Challenges Faced by Perinatally-Infected Kenyan Adolescents and Youth Living with HIV During the COVID-19 Pandemic.

Wellness challenges experienced by adolescents and youth living with HIV (AYLWH) during COVID-19 are unknown and could guide HIV care in resource-limited settings. Between February/2021 and July/2022, perinatally-infected AYLWH at the Academic Model Providing Access to Healthcare (AMPATH) in western Kenya completed surveys assessing psychological, physical, socioeconomic, and antiretroviral nonadherence challenges and underwent viral load (VL) testing evaluating for virologic (VL > 40 copies/mL) or treatment (VL > 1,000 copies/mL) failure. Patterns in challenges, nonadherence, and VL measures by enrolment were evaluated using general additive models.

Stakeholder Perspectives on Research Consent and Reconsent for Procedures Involving Biological Samples and Biobanking of Children and Adolescents Living With HIV in Kenya.

Objective: To explore the perspectives of stakeholders on consenting and reconsenting children and adolescents living with HIV (CALWH) to participate in research involving biological sampling and biobanking. Stakeholders included CALWH, their caregivers, subject matter experts (SMEs) such as Institutional Review Board (IRB) members, Community Advisory Board (CAB) members, Healthcare Providers, researchers, and community leaders.

Study Design: This qualitative study was conducted at the Academic Model Providing Access to Healthcare (AMPATH) in Kenya.

Prospective Evaluation of Routine Statewide Integration of Molecular Epidemiology and Contact Tracing to Disrupt Human Immunodeficiency Virus Transmission.

Background: Human immunodeficiency virus (HIV) remains a global challenge and novel measures for transmission disruption are needed. Contact tracing is limited by reluctance or inability of newly diagnosed individuals to name at-risk contacts. Molecular cluster analysis is mostly used for outbreak investigations, and its role in routine public health activities remains uncertain.

Limited Short-Term Evolution of SARS-CoV-2 RNA-Dependent RNA Polymerase under Remdesivir Exposure in Upper Respiratory Compartments.

Background: The extent of the SARS-CoV-2 short-term evolution under Remdesivir (RDV) exposure and whether it varies across different upper respiratory compartments are not fully understood.

Methods: Patients hospitalized for COVID-19, with or without RDV therapy, were enrolled and completed up to three visits, in which they provided specimens from four respiratory compartments. Near full-length genome SARS-CoV-2 sequences were obtained from viral RNA, standard lineage and variant assignments were performed, and viral mutations in the RNA-dependent RNA polymerase (RdRp) region-the RDV target gene-were detected and compared between participants with and without RDV, across the four compartments, within participants across visits, and versus a larger sequence dataset.

Challenges and Opportunities with at-Home Blood Collection for HIV-1 Viral Load Monitoring among Sexual Minoritized Men who use Stimulants.

Sexually minoritized men (SMM) with HIV who use stimulants experience difficulties achieving and maintaining an undetectable viral load (VL). Home-based VL monitoring could augment HIV care by supporting interim, early identification of detectable VL. We describe implementation challenges associated with a home-collection device for laboratory-based VL testing among SMM with HIV who use stimulants.

Integrating HIV Cluster Analysis in Everyday Public Health Practice: Lessons Learned From a Public Health--Academic Partnership.

Background: The use of molecular HIV cluster analysis to supplement public health contact tracing has shown promise in addressing HIV outbreaks. However, the potential of HIV cluster analysis as an adjunct to daily, person-by-person HIV prevention efforts remains unknown. We documented lessons learned within a unique public health-academic partnership while guiding workaday HIV prevention efforts with near-real-time molecular cluster analysis.

Acquired Human Immunodeficiency Virus Type 1 Drug Resistance in Rhode Island, USA, 2004-2021.

Background: Human immunodeficiency virus type 1 (HIV-1) acquired drug resistance (ADR) compromises antiretroviral therapy (ART).

Methods: We aggregated all HIV-1 protease-reverse transcriptase-integrase sequences over 2004-2021 at the largest HIV center in Rhode Island and evaluated ADR extent, trends, and impact using Stanford Database tools. Trends were measured with Mann-Kendall statistic, and multivariable regressions evaluated resistance predictors.

Ethical Considerations for Engaging Children and Adolescents Living with HIV in Research in African Countries: A Systematic Review.

Research engaging children and adolescents living with HIV (CALWH) is critical for youth-friendly services and HIV care, and researchers need to ensure that such engagement is ethical. We conducted a systematic review to identify key ethical considerations for the engagement of CALWH in research. The review focused on primary research articles conducted in African countries that examined ethical issues in CALWH engaged in research.

Recommendations on data sharing in HIV drug resistance research.

 • Human immunodeficiency virus (HIV) drug resistance has implications for antiretroviral treatment strategies and for containing the HIV pandemic because the development of HIV drug resistance leads to the requirement for antiretroviral drugs that may be less effective, less well-tolerated, and more expensive than those used in first-line regimens.  • HIV drug resistance studies are designed to determine which HIV mutations are selected by antiretroviral drugs and, in turn, how these mutations affect antiretroviral drug susceptibility and response to future antiretroviral treatment regimens.  • Such studies collectively form a vital knowledge base essential for monitoring global HIV drug resistance trends, interpreting HIV genotypic tests, and updating HIV treatment guidelines.

Ethical Considerations for Engaging Youth Living with HIV in Research: Perspectives from Youth, Their Caregivers and Subject Matter Experts in Kenya.

Engaging youth living with HIV (YLWH) in research is critical to improving HIV-related outcomes, but their involvement raises unaddressed bioethical questions. This study used qualitative inquiry with Kenyan YLWH, caregivers, and subject matter experts (SMEs) to evaluate ethical considerations and strategies for research involving YLWH. Interviews were conducted with 99 participants: 40 YLWH (median age 17.

Added Value of Next Generation Sequencing in Characterizing the Evolution of HIV-1 Drug Resistance in Kenyan Youth.

Drug resistance remains a global challenge in children and adolescents living with HIV (CALWH). Characterizing resistance evolution, specifically using next generation sequencing (NGS) can potentially inform care, but remains understudied, particularly in antiretroviral therapy (ART)-experienced CALWH in resource-limited settings. We conducted reverse-transcriptase NGS and investigated short-and long-term resistance evolution and its predicted impact in a well-characterized cohort of Kenyan CALWH failing 1st-line ART and followed for up to ~8 years.

Tree-based subgroup discovery using electronic health record data: heterogeneity of treatment effects for DTG-containing therapies.

The rich longitudinal individual level data available from electronic health records (EHRs) can be used to examine treatment effect heterogeneity. However, estimating treatment effects using EHR data poses several challenges, including time-varying confounding, repeated and temporally non-aligned measurements of covariates, treatment assignments and outcomes, and loss-to-follow-up due to dropout. Here, we develop the subgroup discovery for longitudinal data algorithm, a tree-based algorithm for discovering subgroups with heterogeneous treatment effects using longitudinal data by combining the generalized interaction tree algorithm, a general data-driven method for subgroup discovery, with longitudinal targeted maximum likelihood estimation.