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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. From March-May 2022, cisgender SMM with HIV reporting moderate-to-severe stimulant use disorder and suboptimal (< 90%) past-month antiretroviral therapy (ART) adherence were recruited via a consent-to-contact participant registry. Eligible men completed teleconference-based informed consent and were mailed a HemaSpot-HD blood collection device (volume capacity 160 µL; lower limit of detection 839 copies/mL) with detailed instructions for home blood self-collection and return shipment. Implementation process measures included estimated blood volume and VL quantification. Among 24 participants, 21 (88%) returned specimens with a median duration of 23 days (range: 10-71 days) between sending devices to participants and receiving specimens. Of these, 13/21 (62%) included enough blood (≥ 40 µL) for confidence in detectable/undetectable results; 10/13 (77%) had detectable VL, with 4/10 (40%) were quantifiable at ≥ 839 copies/mL. The remaining 8/21 had low blood volume (< 40 µL), but 3/8 (38%) still had detectable VL, with 1/3 (33%) quantifiable at ≥ 839 copies/mL. Home blood collection of ≥ 40 µL using HemaSpot-HD was feasible among this high-priority population, with > 50% having a VL detected. However, interim VL monitoring using HemaSpot-HD among those experiencing difficulties with ART adherence may be strengthened by building rapport via teleconferencing and providing detailed instructions to achieve adequate sample volume.
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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. SETTING: A public health-academic partnership in the State of Rhode Island, the United States. METHODS: We recorded perceptions of our team of academicians and public health practitioners that were encountered in an 18-month study evaluating the integration of molecular cluster analysis with HIV contact tracing for public health benefit. The focus was on monthly conferences where molecular clustering of each new statewide diagnosis was discussed to facilitate targeted interventions and on attempted reinterviews of all newly HIV-diagnosed persons statewide whose HIV sequences clustered to increase partner naming. RESULTS: Three main themes emerged: First, multidisciplinary conferences are substantially beneficial for gleaning actionable inferences from integrating molecular cluster analysis and public health data. Second, universal reinterviews were perceived to potentially have negative consequences but may be selectively beneficial. Third, the translation of cluster analysis into public health action is hampered by jurisdictional surveillance boundaries and within-jurisdictional data silos, across which data sharing is problematic. CONCLUSIONS: Insights from a statewide public health-academic partnership support integration of molecular HIV cluster analyses with public health efforts, which can guide public health activities to prevent transmission while identifying substantial barriers to integration, informing continued research.
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Trazado de Contacto , Infecciones por VIH , Humanos , Infecciones por VIH/prevención & control , Infecciones por VIH/epidemiología , Análisis por Conglomerados , Rhode Island/epidemiología , Práctica de Salud Pública , Salud PúblicaRESUMEN
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. RESULTS: Sequences were available for 914 ART-experienced persons. Overall ADR to any drug decreased from 77% to 49% (-0.66 Mann-Kendall statistic); nucleoside reverse transcriptase inhibitors 65% to 32%, nonnucleoside reverse transcriptase inhibitors 53% to 43%, and protease inhibitors 28% to 7% (2004-2021), and integrase strand transfer inhibitors 16% to 13% (2017-2021). Multiclass resistance decreased from 44% to 12% (2-class) and 12% to 6% (3-class). In 2021, 94% had at least one 3-drug or 2-drug one-pill-once-daily (OPOD) option. Males and those exposed to more ART regimens were more likely to have ≥2-class resistance, and higher regimen exposure was also associated with fewer OPOD options. CONCLUSIONS: Comprehensive analyses within a densely-sampled HIV epidemic over 2004-2021 demonstrated decreasing ADR. Continued ADR monitoring is important to maintain ART success, particularly with rising INSTI use in all lines of therapy and 2-drug and long-acting formulations.
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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. We apply the algorithm to EHR data to discover subgroups of people living with human immunodeficiency virus who are at higher risk of weight gain when receiving dolutegravir (DTG)-containing antiretroviral therapies (ARTs) versus when receiving non-DTG-containing ARTs.
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Registros Electrónicos de Salud , Infecciones por VIH , Compuestos Heterocíclicos con 3 Anillos , Piperazinas , Piridonas , Humanos , Heterogeneidad del Efecto del Tratamiento , Oxazinas , Infecciones por VIH/tratamiento farmacológicoRESUMEN
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. Ten studies met the inclusion criteria; the following seven key domains were extracted: 1) justifications for engaging CALWH in research; 2) community involvement; 3) informed consent/assent; 4) caregiver involvement; 5) perceptions of benefits; 6) perception of the risks of involvement; and 7) confidentiality. These domains can inform the ethical engagement of CALWH in research.
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Participación de la Comunidad , Infecciones por VIH , Humanos , Adolescente , Niño , Consentimiento Informado , Investigadores , Encuestas y CuestionariosRESUMEN
⢠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. ⢠Although HIV drug resistance data are collected in many studies, such data are often not publicly shared, prompting the need to recommend best practices to encourage and standardize HIV drug resistance data sharing. ⢠In contrast to other viruses, sharing HIV sequences from phylogenetic studies of transmission dynamics requires additional precautions as HIV transmission is criminalized in many countries and regions. ⢠Our recommendations are designed to ensure that the data that contribute to HIV drug resistance knowledge will be available without undue hardship to those publishing HIV drug resistance studies and without risk to people living with HIV.
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Fármacos Anti-VIH , Infecciones por VIH , VIH-1 , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Filogenia , VIH-1/genética , Farmacorresistencia Viral/genética , Antirretrovirales/uso terapéutico , Mutación , Fármacos Anti-VIH/farmacología , Fármacos Anti-VIH/uso terapéuticoRESUMEN
Introduction: Engaging youth living with HIV (YLWH) in research is critical to improving HIV-related outcomes, but their involvement raises unaddressed bioethical questions. Methods: This study used qualitative inquiry with Kenyan YLWH, caregivers, and subject matter experts (SMEs) to evaluate ethical considerations and strategies for research involving YLWH. Results: Interviews were conducted with 99 participants: 40 YLWH (median age 17.5, 50% female), 20 caregivers (70% female), and 39 SMEs (44% female). All participant groups discussed the need for HIV disclosure status assessment, confidentiality, and engagement of caregivers. Youth participants discussed the importance of clear protocol explanations and developing good rapport. All participant groups perceived youth under 18 to be harder to recruit due to a number of identified barriers. Clinic settings were the most acceptable place for recruitment. Conclusion: Participants provided perspectives on engaging YLWH in research that can be incorporated into protocols and regulatory guidelines.
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Infecciones por VIH , VIH , Humanos , Adolescente , Femenino , Masculino , Kenia , Cuidadores , RevelaciónRESUMEN
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. Drug resistance mutation (DRM) evolution types were determined by NGS frequency changes over time, defined as evolving (up-trending and crossing the 20% NGS threshold), reverting (down-trending and crossing the 20% threshold) or other. Exploratory analyses assessed potential impacts of minority resistance variants on evolution. Evolution was detected in 93% of 42 participants, including 91% of 22 with short-term follow-up, 100% of 7 with long-term follow-up without regimen change, and 95% of 19 with long-term follow-up with regimen change. Evolving DRMs were identified in 60% and minority resistance variants evolved in 17%, with exploratory analysis suggesting greater rate of evolution of minority resistance variants under drug selection pressure and higher predicted drug resistance scores in the presence of minority DRMs. Despite high-level pre-existing resistance, NGS-based longitudinal follow-up of this small but unique cohort of Kenyan CALWH demonstrated continued DRM evolution, at times including low-level DRMs detected only by NGS, with predicted impact on care. NGS can inform better understanding of DRM evolution and dynamics and possibly improve care. The clinical significance of these findings should be further evaluated.
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Fármacos Anti-VIH , Infecciones por VIH , Seropositividad para VIH , VIH-1 , Niño , Humanos , Adolescente , VIH-1/genética , Kenia , Secuenciación de Nucleótidos de Alto Rendimiento , Farmacorresistencia Viral/genética , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/genética , Mutación , Fármacos Anti-VIH/farmacología , Fármacos Anti-VIH/uso terapéutico , GenotipoRESUMEN
Introduction: HIV stigma affects medication adherence, psychosocial outcomes, and clinical management for youth living with HIV (YLWH). We explored the impact of HIV stigma on research participation, to inform the ethical engagement of this vulnerable group. Methods: We interviewed 40 YLWH, 20 caregivers, and 39 subject matter experts (SMEs); transcripts were analyzed by HK and EG, with emerging themes confirmed by JA and AC. Results: All categories of participants identified the impacts of stigma on YLWH research participation, suggesting implementing privacy protections, considering recruitment locations carefully, and developing supportive relationships with YLWH. SMEs suggested that YLWH experience uniquely high risks from stigma due to the compounding effects of developmental challenges and transitionary life period. Accidental HIV disclosure and subsequent stigma were identified as a risk of research participation; some viewed the creation of community through research as a benefit. Conclusion: Participants provided insights into stigma-related considerations for research with YLWH, which may guide engagement protocols.
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Infecciones por VIH , Humanos , Adolescente , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/psicología , VIH , Kenia , Estigma Social , Cumplimiento de la MedicaciónRESUMEN
Molecular HIV cluster data can guide public health responses towards ending the HIV epidemic. Currently, real-time data integration, analysis, and interpretation are challenging, leading to a delayed public health response. We present a comprehensive methodology for addressing these challenges through data integration, analysis, and reporting. We integrated heterogeneous data sources across systems and developed an open-source, automatic bioinformatics pipeline that provides molecular HIV cluster data to inform public health responses to new statewide HIV-1 diagnoses, overcoming data management, computational, and analytical challenges. We demonstrate implementation of this pipeline in a statewide HIV epidemic and use it to compare the impact of specific phylogenetic and distance-only methods and datasets on molecular HIV cluster analyses. The pipeline was applied to 18 monthly datasets generated between January 2020 and June 2022 in Rhode Island, USA, that provide statewide molecular HIV data to support routine public health case management by a multi-disciplinary team. The resulting cluster analyses and near-real-time reporting guided public health actions in 37 phylogenetically clustered cases out of 57 new HIV-1 diagnoses. Of the 37, only 21 (57%) clustered by distance-only methods. Through a unique academic-public health partnership, an automated open-source pipeline was developed and applied to prospective, routine analysis of statewide molecular HIV data in near-real-time. This collaboration informed public health actions to optimize disruption of HIV transmission.
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Infecciones por VIH , Seropositividad para VIH , VIH-1 , Humanos , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Salud Pública , Filogenia , Estudios Prospectivos , VIH-1/genéticaRESUMEN
Characterizing HIV-related stigma and its impacts are important for interventions toward their elimination. A cross-sectional study was conducted in 2016 to evaluate enacted and internalized stigma among adult people living with HIV (PLWH) across four cities in Myanmar using the India Stigma Index questionnaire. Multivariable regression analyses were performed to determine differences in measured enacted and internalized stigma outcomes. Among 1,006 participants, 89% reported any stigma indicator, 47% enacted stigma, and 87% internalized stigma. In regression analysis, city and duration of illness were associated with higher enacted stigma, and younger age was associated with higher internalized stigma. Those with HIV duration > 7.4 years had mean enacted stigma nearly 2 units higher than the overall mean. Internalized stigma increased with duration of illness and leveled off at 5 years. PLWH from smaller cities experienced lower stigma. In Myanmar, nearly 90% of PLWH experience stigma, results that reflect a unique transition point.
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Infecciones por VIH , Adulto , Humanos , Estudios Transversales , Mianmar , Infecciones por VIH/epidemiología , Estigma Social , CiudadesRESUMEN
OBJECTIVES: Molecular epidemiology is a powerful tool to characterize HIV epidemics and prioritize public health interventions. Typically, HIV clusters are assumed to have uniform patterns over time. We hypothesized that assessment of cluster evolution would reveal distinct cluster behavior, possibly improving molecular epidemic characterization, towards disrupting HIV transmission. DESIGN: Retrospective cohort. METHODS: Annual phylogenies were inferred by cumulative aggregation of all available HIV-1 pol sequences of individuals with HIV-1 in Rhode Island (RI) between 1990 and 2020, representing a statewide epidemic. Molecular clusters were detected in annual phylogenies by strict and relaxed cluster definition criteria, and the impact of annual newly-diagnosed HIV-1 cases to the structure of individual clusters was examined over time. RESULTS: Of 2153 individuals, 31% (strict criteria) - 47% (relaxed criteria) clustered. Longitudinal tracking of individual clusters identified three cluster types: normal, semi-normal and abnormal. Normal clusters (83-87% of all identified clusters) showed predicted growing/plateauing dynamics, with approximately three-fold higher growth rates in large (15-18%) vs. small (â¼5%) clusters. Semi-normal clusters (1-2% of all clusters) temporarily fluctuated in size and composition. Abnormal clusters (11-16% of all clusters) demonstrated collapses and re-arrangements over time. Borderline values of cluster-defining parameters explained dynamics of non-normal clusters. CONCLUSIONS: Comprehensive tracing of molecular HIV clusters over time in a statewide epidemic identified distinct cluster types, likely missed in cross-sectional analyses, demonstrating that not all clusters are equal. This knowledge challenges current perceptions of consistent cluster behavior over time and could improve molecular surveillance of local HIV epidemics to better inform public health strategies.
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Infecciones por VIH , Seropositividad para VIH , VIH-1 , Humanos , VIH-1/genética , Rhode Island/epidemiología , Infecciones por VIH/epidemiología , Estudios Transversales , Estudios Retrospectivos , Análisis por Conglomerados , Filogenia , Epidemiología MolecularRESUMEN
HIV drug resistance is a major global hurdle to successful and sustained antiretroviral therapy. Global guidelines recommend testing for antiretroviral drug resistance and results are used to inform treatment regimen design for patients at different stages of therapy. Several clinical trials investigated optimal regimens after failure of first-line antiretroviral therapy, yielding data that advanced knowledge and informed care. However, further interpretation of data from these studies questioned the benefit of antiretroviral drug resistance testing for cases in which first-line treatment is not effective and, furthermore, that relying on the results of antiretroviral drug resistance testing could be misleading and unnecessary. In this Viewpoint, which is largely focused on high-income settings, we review these data, reflect on the potential problems with their interpretation, and call for caution in their extrapolation. Without negating the importance of the data, and recognising the varied circumstances related to HIV drug resistance testing in different global settings, we advise caution before changing current practice and recommendations. We believe that we should not universally stop considering HIV drug resistance testing at failure of first-line antiretroviral therapy.
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Fármacos Anti-VIH , Infecciones por VIH , Humanos , Infecciones por VIH/tratamiento farmacológico , Fármacos Anti-VIH/uso terapéutico , Farmacorresistencia Viral , Terapia Antirretroviral Altamente Activa/efectos adversos , Antirretrovirales/uso terapéutico , Insuficiencia del Tratamiento , Carga ViralRESUMEN
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.gisaid.org. Genomic analyses were conducted to identify variants of concern (VOC), variants being monitored (VBM), or non-VOC/non-VBM, and investigate their evolution. RESULTS: Overall, 17,340 SARS-CoV-2 RI sequences were available between 2/2020-5/2022 across five (globally recognized) major waves, including 1,462 (8%) sequences from 36 non-VOC/non-VBM until 5/2021; 10,565 (61%) sequences from 8 VBM between 5/2021-12/2021, most commonly Delta; and 5,313 (31%) sequences from the VOC Omicron from 12/2021 onwards. Genomic analyses demonstrated 71 Delta and 44 Omicron sub-lineages, with occurrence of variant-defining mutations in other variants. CONCLUSION: Statewide SARS-CoV-2 genomic surveillance allows for continued characterization of circulating variants and monitoring of viral evolution, which inform the local health force and guide public health on mitigation efforts against COVID-19.
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COVID-19 , SARS-CoV-2 , COVID-19/epidemiología , Genoma Viral , Humanos , Rhode Island/epidemiología , SARS-CoV-2/genéticaRESUMEN
INTRODUCTION: Adolescents living with HIV (ALHIV, ages 10-19) experience complex barriers to care engagement. Challenges surrounding HIV status disclosure or non-disclosure to adolescents may contribute to adolescent disengagement from HIV care or non-adherence to ART. We performed a qualitative study to investigate the contribution of disclosure challenges to adolescent disengagement from HIV care. METHODS: This was a qualitative study performed with disengaged ALHIV and their caregivers, and with healthcare workers (HCW) in the Academic Model Providing Access to Healthcare (AMPATH) program in western Kenya. Inclusion criteria for ALHIV were ≥1 visit within the 18 months prior to data collection at one of two clinical sites and nonattendance ≥60 days following their last scheduled appointment. HCW were recruited from 10 clinics. Analysis was conducted by multiple independent coders, and narratives of disclosure and care disengagement were closely interrogated. Overarching themes were elucidated and summarized. RESULTS: Interviews were conducted with 42 disengaged ALHIV, 32 caregivers, and 28 HCW. ALHIV were average age 17.0 (range 12.9-20.9), and 95% indicated awareness of their HIV diagnosis. Issues surrounding disclosure to ALHIV presented important barriers to HIV care engagement. Themes centered on delays in HIV status disclosure; hesitancy and reluctance among caregivers to disclose; struggles for adolescents to cope with feelings of having been deceived prior to full disclosure; pervasive HIV stigma internalized in school and community settings prior to disclosure; and inadequate and unstructured support after disclosure, including for adolescent mental health burdens and for adolescent-caregiver relationships and communication. Both HCW and caregivers described feeling inadequately prepared to optimally handle disclosure and to manage challenges that may arise after disclosure. CONCLUSIONS: Complex challenges surrounding HIV status disclosure to adolescents contribute to care disengagement. There is need to enhance training and resources for HCW, and to empower caregivers to support children and adolescents before, during, and after HIV status disclosure. This should include counseling caregivers on how to provide children with developmentally-appropriate and accurate information about their health from an early age, and to support adolescent-caregiver communication and relationships. Optimally integrating peer support can further promote ALHIV wellbeing and retention in care.
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Revelación , Infecciones por VIH , Adolescente , Adulto , Cuidadores , Niño , Infecciones por VIH/diagnóstico , Infecciones por VIH/psicología , Infecciones por VIH/terapia , Humanos , Kenia , Investigación Cualitativa , Estigma Social , Adulto JovenRESUMEN
Characterizing HIV acquisition modes among adolescents with HIV (AHIV) enrolling in care during adolescence is a challenging gap that impacts differential interventions. We explored whether primary data collection with targeted questionnaires may address this gap and improve understanding of risk factors and perceptions about adolescents' HIV acquisition, in Kenyan AHIV entering care at ≥10 years, and their mothers with HIV (MHIV). Clinical data were derived through chart review. Among 1073 AHIV in care, only 26 (2%) met eligibility criteria of being ≥10 years at care enrollment, disclosed to, and with living MHIV. Among 18/26 AHIV-MHIV dyads enrolled (median age of AHIV 14 years), none had documented HIV acquisition modes. Data suggested perinatal infection in 17/18 AHIV, with 1 reported non-perinatal acquisition risk factor, and some discordance between adolescent-mother perceptions of HIV acquisition. In this difficult-to-enroll, vulnerable population of AHIV-MHIV dyads, primary data collection can enhance understanding of AHIV acquisition modes.
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INTRODUCTION: HIV continues to have great impact on millions of lives. Novel methods are needed to disrupt HIV transmission networks. In the USA, public health departments routinely conduct contact tracing and partner services and interview newly HIV-diagnosed index cases to obtain information on social networks and guide prevention interventions. Sequence clustering methods able to infer HIV networks have been used to investigate and halt outbreaks. Incorporation of such methods into routine, not only outbreak-driven, contact tracing and partner services holds promise for further disruption of HIV transmissions. METHODS AND ANALYSIS: Building on a strong academic-public health collaboration in Rhode Island, we designed and have implemented a state-wide prospective study to evaluate an intervention that incorporates real-time HIV molecular clustering information with routine contact tracing and partner services. We present the rationale and study design of our approach to integrate sequence clustering methods into routine public health interventions as well as related important ethical considerations. This prospective study addresses key questions about the benefit of incorporating a clustering analysis triggered intervention into the routine workflow of public health departments, going beyond outbreak-only circumstances. By developing an intervention triggered by, and incorporating information from, viral sequence clustering analysis, and evaluating it with a novel design that avoids randomisation while allowing for methods comparison, we are confident that this study will inform how viral sequence clustering analysis can be routinely integrated into public health to support the ending of the HIV pandemic in the USA and beyond. ETHICS AND DISSEMINATION: The study was approved by both the Lifespan and Rhode Island Department of Health Human Subjects Research Institutional Review Boards and study results will be published in peer-reviewed journals.
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Infecciones por VIH , Salud Pública , Análisis por Conglomerados , Brotes de Enfermedades/prevención & control , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Humanos , Estudios ProspectivosRESUMEN
The SARS-CoV-2 Delta variant rose to dominance in mid-2021, likely propelled by an estimated 40%-80% increased transmissibility over Alpha. To investigate if this ostensible difference in transmissibility is uniform across populations, we partner with public health programs from all six states in New England in the United States. We compare logistic growth rates during each variant's respective emergence period, finding that Delta emerged 1.37-2.63 times faster than Alpha (range across states). We compute variant-specific effective reproductive numbers, estimating that Delta is 63%-167% more transmissible than Alpha (range across states). Finally, we estimate that Delta infections generate on average 6.2 (95% CI 3.1-10.9) times more viral RNA copies per milliliter than Alpha infections during their respective emergence. Overall, our evidence suggests that Delta's enhanced transmissibility can be attributed to its innate ability to increase infectiousness, but its epidemiological dynamics may vary depending on underlying population attributes and sequencing data availability.
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COVID-19 , SARS-CoV-2 , COVID-19/epidemiología , Humanos , New England/epidemiología , Salud Pública , SARS-CoV-2/genéticaRESUMEN
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. Samples were shipped in real-time at ambient temperature to the US, and those with viral load (VL)>1,000 copies/mL were tested based on convenience. Dried blood spots genotyping was attempted when unsuccessful from Hemaspots. Multiple logistic regression was used to examine predictors of genotyping success. Samples from 49 participants (median age 15 years, 43% female, median CD4 496 cells/µL [18%], median 8 years on therapy, median VL 11,827 copies/mL) were shipped after median 7 days from collection, arrived in 20 shipments after median 5 days, and extracted after median 2 days (1 day for samples processed on arrival; and 42 days for frozen Hemaspots). Overall, 29/49 (59%) samples with VL > 1,000 copies/mL and 25/32 (78%) with VL > 5,000 copies/mL were genotyped by either Hemaspots or DBS. Successful genotyping was associated with higher Hemaspot volume and higher VL. Real-life HIV-1 drug resistance testing from dried filter analytes is feasible, even in settings with constrained resources. Findings, particularly relevant where resistance testing is limited for clinical care, raise awareness to implementation practicability of this guidelines-recommended test in care of more individuals and populations. Further optimization of filter analytes is needed to overcome related challenges. IMPORTANCE In this manuscript we use dried filter analytes shipped from Kenya to the US in real time, to demonstrate the real-life feasibility of conducting HIV drug resistance testing in a vulnerable population of young children and adolescents with HIV in a resource limited setting. Such testing, which is recommended in resource-rich settings, is unavailable in most resource limited settings for individual clinical care. We show that real-life HIV drug resistance testing from dried filter analytes is feasible, even in settings with constrained resources. These findings raise awareness to the importance of HIV drug resistance for individual care, even in such settings, and emphasize the implementation practicability of this guidelines-recommended test.