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.

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.

SARS-CoV-2 Variants in Rhode Island; May 2022 Update.

Background: Genomic surveillance allows identification of circulating SARS-CoV-2 variants. We provide an update on the evolution of SARS-CoV-2 in Rhode Island (RI).

Methods: All publicly available SARS-CoV-2 RI sequences were retrieved from https://www.

The role of CYP2B6 516G>T polymorphism on efavirenz/nevirapine toxicity. Implications on treatment outcomes: Lessons from Botswana.

The two non-nucleoside reverse transcriptase inhibitors (NNRTIs), efavirenz (EFV) and nevirapine (NVP), are currently the core antiretroviral drugs for treatment of HIV in sub-Saharan Africa including Botswana. The drugs are metabolized by Cytochrome P450 2B6 (CYP2B6) liver enzyme. The CYP2B6 gene that encodes for metabolism of these drugs is known to be highly polymorphic.

Real-Life Feasibility of HIV Drug Resistance Testing Using Dried Filter Analytes in Kenyan Children and Adolescents Living with HIV.

HIV-1 drug resistance remains a global challenge, yet access to testing is limited, particularly in resource-limited settings. We examined feasibility and limitations of genotyping using dried filter analytes in treatment-experienced Kenyan youth with HIV. Youth infected with HIV perinatally were enrolled in 2016-2018 at the Academic Model Providing Access to Healthcare in Eldoret, western Kenya.

Deep-sequence phylogenetics to quantify patterns of HIV transmission in the context of a universal testing and treatment trial - BCPP/Ya Tsie trial.

Background: Mathematical models predict that community-wide access to HIV testing-and-treatment can rapidly and substantially reduce new HIV infections. Yet several large universal test-and-treat HIV prevention trials in high-prevalence epidemics demonstrated variable reduction in population-level incidence.

Methods: To elucidate patterns of HIV spread in universal test-and-treat trials, we quantified the contribution of geographic-location, gender, age, and randomized-HIV-intervention to HIV transmissions in the 30-community Ya Tsie trial in Botswana.

HIV-1 Treatment Failure, Drug Resistance, and Clinical Outcomes in Perinatally Infected Children and Adolescents Failing First-Line Antiretroviral Therapy in Western Kenya.

Background: Long-term impact of drug resistance in perinatally infected children and adolescents living with HIV (CALWH) is poorly understood. We determined drug resistance and examined its long-term impact on failure and mortality in Kenyan CALWH failing first-line non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy (ART).

Setting: Academic Model Providing Access to Healthcare, western Kenya.

Limited HIV-1 Subtype C 3'PPT Variation in Combination Antiretroviral Therapy Naïve and Experienced People Living with HIV in Botswana.

Dolutegravir (DTG) is a potent anti-HIV drug that is used to treat HIV globally. There have been reports of mutations in the HIV-1 3'-polypurine tract (3'PPT) of the gene, contributing to DTG failure; however, there are limited 'real-world' data on this. In addition, there is a knowledge gap on the variability of 3'PPT residues in patients receiving combination antiretroviral therapy (cART) with and without viral load (VL) suppression.

SARS-CoV-2 Variants in Rhode Island.

COVID-19 is a worldwide public health emergency caused by SARS-CoV-2. Genomic surveillance of SARS-CoV-2 emerging variants is important for pandemic monitoring and informing public health responses. Through an interstate academic-public health partnership, we established Rhode Island's capacity to sequence SARS-CoV-2 genomes and created a systematic surveillance program to monitor the prevalence of SARS-CoV-2 variants in the state.

HIV Drug Resistance and Transmission Networks Among a Justice-Involved Population at the Time of Community Reentry in Washington, D.C.

Justice-involved (JI) populations bear a disproportionate burden of HIV infection and are at risk of poor treatment outcomes. Drug resistance prevalence and emergence, and phylogenetic inference of transmission networks, understudied in vulnerable JI populations, can inform care and prevention interventions, particularly around the critical community reentry period. We analyzed banked blood specimens from CARE+ Corrections study participants in Washington, D.

Association of Genetic Variation with Efavirenz and Nevirapine Drug Resistance in HIV-1 Patients from Botswana.

Purpose: CYP2B6 liver enzyme metabolizes the two non-nucleoside reverse transcriptase inhibitors Efavirenz (EFV) and Nevirapine (NVP) used in the antiretroviral therapy (ART) regimens for HIV-infected individuals. Polymorphisms of the gene influence drug levels in plasma and possibly virological outcomes. The aim of this study was to explore the potential impact of genotype and haplotype variation on the risk of developing EFV/NVP drug resistance mutations (DRMs) in HIV-1 patients receiving EFV-/NVP-containing regimens in Botswana.

Detection of Inducible Replication-Competent HIV-1 Subtype C Provirus Despite Long-Term Antiretroviral Treatment in Perinatally Infected Adolescents in Botswana.

Although antiretroviral therapy (ART) effectively suppresses HIV replication, the latent reservoir remains the barrier to HIV eradication. It remains unknown whether long-term ART impacts levels of inducible replication-competent provirus. To address this knowledge gap, we assessed the proviral reservoir in HIV-1 perinatally infected adolescents having received ART for >13 years.

Challenges in evaluating the use of viral sequence data to identify HIV transmission networks for public health.

Great efforts are devoted to end the HIV epidemic as it continues to have profound public health consequences in the United States and throughout the world, and new interventions and strategies are continuously needed. The use of HIV sequence data to infer transmission networks holds much promise to direct public heath interventions where they are most needed. As these new methods are being implemented, evaluating their benefits is essential.

Joint penalized spline modeling of multivariate longitudinal data, with application to HIV-1 RNA load levels and CD4 cell counts.

Motivated by the need to jointly model the longitudinal trajectories of HIV viral load levels and CD4 counts during the primary infection stage, we propose a joint penalized spline modeling approach that can be used to model the repeated measurements from multiple biomarkers of various types (eg, continuous, binary) simultaneously. This approach allows for flexible trajectories for each marker, accounts for potentially time-varying correlation between markers, and is robust to misspecification of knots. Despite its advantages, the application of multivariate penalized spline models, especially when biomarkers may be of different data types, has been limited in part due to its seemingly complexity in implementation.

Undetectable proviral deoxyribonucleic acid in an adolescent perinatally infected with human immunodeficiency virus-1C and on long-term antiretroviral therapy resulted in viral rebound following antiretroviral therapy termination: A case report with implications for clinical care.

Rationale: Early initiation of antiretroviral therapy (ART) leads to long-term viral suppression, reduces proviral reservoir size, and prolongs time to rebound. Since human immunodeficiency virus (HIV) is a lifelong disease, diagnostic monitoring after confirmed infection is typically not performed; therefore, little is known about the impact of early initiation and long-term ART on the sensitivity of assays that detect HIV antibodies and viral nucleic acid in children and adolescents.

Patient Concerns: Here we report 1 case of diagnosed and confirmed perinatal HIV-1C infection with longstanding viral suppression, who subsequently had a negative HIV-1 deoxyribonucleic acid (DNA) test, undetectable antibodies to HIV-1, and high CD4+ T cell count after 14 years of ART.

Comparison of knowledge of HIV status and treatment coverage between non-citizens and citizens: Botswana Combination Prevention Project (BCPP).

Introduction: Non-citizens often face barriers to HIV care and treatment. Quantifying knowledge of positive HIV status and antiretroviral therapy (ART) coverage among non-citizens in a high HIV-prevalence country like Botswana that is close to achieving UNAIDS "90-90-90" targets may expose important gaps in achieving universal HIV testing and treatment.

Methods: The Botswana Combination Prevention Project (BCPP) is a pair-matched cluster-randomized trial evaluating the impact of prevention interventions on HIV incidence in 30 rural or peri-urban communities.

Genetic diversity of Mycobacterium tuberculosis strains circulating in Botswana.

Background: Molecular typing of Mycobacterium tuberculosis (M.tb) isolates can inform Tuberculosis (TB) control programs on the relative proportion of transmission driving the TB epidemic. There is limited data on the M.

The Changing Epidemiological Profile of HIV-1 Subtype B Epidemic in Ukraine.

While HIV-1 subtype B has caused a large epidemic in the Western world, its transmission in Ukraine remains poorly understood. We assessed the genetic diversity of HIV-1 subtype B viruses circulating in Ukraine, characterized the transmission group structure, and estimated key evolutionary and epidemiological parameters. We analyzed 120 HIV-1 subtype B pol sequences (including 46 newly generated) sampled from patients residing in 11 regions of Ukraine between 2002 and 2017.

Ethical considerations in global HIV phylogenetic research.

Phylogenetic analysis of pathogens is an increasingly powerful way to reduce the spread of epidemics, including HIV. As a result, phylogenetic approaches are becoming embedded in public health and research programmes, as well as outbreak responses, presenting unique ethical, legal, and social issues that are not adequately addressed by existing bioethics literature. We formed a multidisciplinary working group to explore the ethical issues arising from the design of, conduct in, and use of results from HIV phylogenetic studies, and to propose recommendations to minimise the associated risks to both individuals and groups.

Pol-Driven Replicative Capacity Impacts Disease Progression in HIV-1 Subtype C Infection.

CD8 T cell-mediated escape mutations in Gag can reduce HIV-1 replication capacity (RC) and alter disease progression, but less is known about immune-mediated attenuation in other HIV-1 proteins. We generated 487 recombinant viruses encoding RT-integrase from individuals with chronic ( = 406) and recent ( = 81) HIV-1 subtype C infection and measured their RC using a green fluorescent protein (GFP) reporter T cell assay. In recently infected individuals, reverse transcriptase (RT)-integrase-driven RC correlated significantly with viral load set point ( 0.

Prevalence of Rilpivirine and Etravirine Resistance Mutations in HIV-1 Subtype C-Infected Patients Failing Nevirapine or Efavirenz-Based Combination Antiretroviral Therapy in Botswana.

Rilpivirine (RPV) and Etravirine (ETR) are approved second-generation non-nucleoside reverse transcriptase inhibitors (NNRTIs) for HIV treatment. There is a cross-resistance HIV mutation profile between first- and second-generation NNRTI drugs. We determined the prevalence of HIV-1 drug resistance mutations (DRMs) to RPV and ETR in Botswana.

High HIV-1 RNA Among Newly Diagnosed People in Botswana.

HIV-1 RNA level is strongly associated with HIV transmission risk. We sought to determine whether HIV-1 RNA level was associated with prior knowledge of HIV status among treatment-naive HIV-infected individuals in Botswana, a country with high rates of antiretroviral treatment (ART) coverage. This information may be helpful in targeting HIV diagnosis and treatment efforts in similar high HIV prevalence settings in a population-based survey.