RESUMO
BACKGROUND: Long COVID, also known as post-acute sequelae of COVID-19 (PASC), is a poorly understood condition with symptoms across a range of biological domains that often have debilitating consequences. Some have recently suggested that lingering SARS-CoV-2 virus particles in the gut may impede serotonin production and that low serotonin may drive many Long COVID symptoms across a range of biological systems. Therefore, selective serotonin reuptake inhibitors (SSRIs), which increase synaptic serotonin availability, may be used to prevent or treat Long COVID. SSRIs are commonly prescribed for depression, therefore restricting a study sample to only include patients with depression can reduce the concern of confounding by indication. METHODS: In an observational sample of electronic health records from patients in the National COVID Cohort Collaborative (N3C) with a COVID-19 diagnosis between September 1, 2021, and December 1, 2022, and a comorbid depressive disorder, the leading indication for SSRI use, we evaluated the relationship between SSRI use during acute COVID-19 and subsequent 12-month risk of Long COVID (defined by ICD-10 code U09.9). We defined SSRI use as a prescription for SSRI medication beginning at least 30 days before acute COVID-19 and not ending before SARS-CoV-2 infection. To minimize bias, we estimated relationships using nonparametric targeted maximum likelihood estimation to aggressively adjust for high-dimensional covariates. RESULTS: We analyzed a sample (n = 302,626) of patients with a diagnosis of a depressive condition before COVID-19 diagnosis, where 100,803 (33%) were using an SSRI. We found that SSRI users had a significantly lower risk of Long COVID compared to nonusers (adjusted causal relative risk 0.92, 95% CI (0.86, 0.99)) and we found a similar relationship comparing new SSRI users (first SSRI prescription 1 to 4 months before acute COVID-19 with no prior history of SSRI use) to nonusers (adjusted causal relative risk 0.89, 95% CI (0.80, 0.98)). CONCLUSIONS: These findings suggest that SSRI use during acute COVID-19 may be protective against Long COVID, supporting the hypothesis that serotonin may be a key mechanistic biomarker of Long COVID.
Assuntos
COVID-19 , SARS-CoV-2 , Inibidores Seletivos de Recaptação de Serotonina , Humanos , COVID-19/epidemiologia , COVID-19/complicações , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Feminino , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/efeitos dos fármacos , Adulto , Idoso , Depressão/tratamento farmacológico , Pandemias , Síndrome de COVID-19 Pós-Aguda , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/complicações , Betacoronavirus/efeitos dos fármacos , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Fatores de RiscoRESUMO
Validation studies are often used to obtain more reliable information in settings with error-prone data. Validated data on a subsample of subjects can be used together with error-prone data on all subjects to improve estimation. In practice, more than one round of data validation may be required, and direct application of standard approaches for combining validation data into analyses may lead to inefficient estimators since the information available from intermediate validation steps is only partially considered or even completely ignored. In this paper, we present two novel extensions of multiple imputation and generalized raking estimators that make full use of all available data. We show through simulations that incorporating information from intermediate steps can lead to substantial gains in efficiency. This work is motivated by and illustrated in a study of contraceptive effectiveness among 83 671 women living with HIV, whose data were originally extracted from electronic medical records, of whom 4732 had their charts reviewed, and a subsequent 1210 also had a telephone interview to validate key study variables.
Assuntos
Confiabilidade dos Dados , Registros Eletrônicos de Saúde , Feminino , Humanos , Infecções por HIVRESUMO
The articles in this special issue of AIDS and Behavior focus on the collision between HIV/AIDS and COVID-19 as intersecting pandemics that profoundly impacted communities globally. This editorial highlights the complex interplay between these two public health crises. The pandemic disrupted access to HIV prevention, testing, and treatment services, potentially jeopardizing decades of progress. Mental health challenges and social vulnerability among people living with HIV (PWH) were exacerbated, with preexisting health disparities amplified, disproportionately affecting marginalized populations. However, despite these challenges, the pandemic also spurred innovation and adaptation in HIV prevention and care, with increased use of telehealth and other modalities. The enduring and actionable lessons learned from the collision of HIV and COVID-19 pandemics can prepare us for the next public health challenge with two calls for action. First, we call for integrated and equitable responses that address the multifaceted challenges faced by individuals and communities affected by HIV in the post-COVID-19 era. Second, we call for a strengthened commitment to building resilient health systems and community-engaged interventions that can withstand future challenges.
Assuntos
COVID-19 , Infecções por HIV , SARS-CoV-2 , Humanos , COVID-19/prevenção & controle , COVID-19/epidemiologia , Infecções por HIV/prevenção & controle , Infecções por HIV/epidemiologia , Pandemias/prevenção & controle , Acessibilidade aos Serviços de Saúde , Telemedicina , Saúde Pública , Disparidades em Assistência à SaúdeRESUMO
In the U.S., inequities by race/ethnicity in health outcomes, such as in the HIV epidemic, are long standing but have come to the forefront during the COVID-19 pandemic. There is growing recognition of the role of structural racism in racialized health inequities, yet the conceptualization and operationalization of structural racism in HIV research lags. We conducted a scoping review of existing published literature, between 1999-April 2024, conceptualizing and measuring structural racism's impact among people living with or at risk for HIV in the U.S. Our initial search yielded 236 unique articles, which after title and abstract screening yielded ten articles meeting full text review criteria. We then extracted key parameters, such as conceptualization, method of measurement of structural racism, study aims, design, and findings. Three of the articles were qualitative studies that conceptualized structural racism using (1) the social network model, (2) individual and structural intersectionality and (3) critical race theory. Operationalization of structural racism within the seven quantitative studies fell into three categories: (1) structural level, (2) a scale of experiences of racism, including structural racism, and (3) using explanatory demographic factors as downstream measures of the effects of structural racism. The variance in the conceptualization and operationalization of structural racism highlights the different interpretations of structural racism in its applications to the field of HIV research. Given the vast racial/ethnic inequities in HIV, we propose three overarching suggestions for next steps in improving the conduct of research on structural racism in HIV: (1) we must prioritize measuring racism past the individual and interpersonal levels to consider systemic factors at a societal level that manifest as structural racism to improve HIV outcomes in the U.S., (2) consider intergenerational effects of structural racism through the use of longitudinal data, and (3) broaden the agenda of structural racism to incorporate other systems of oppression. Additionally, broadening the scope of funding and inclusion of more researchers and individuals with lived experiences to support structural racism research to drive the scientific agenda and design of structural-level interventions will not only bolster achieving the U.S. Ending the HIV Epidemic goals but will do so by addressing inequities.
Assuntos
COVID-19 , Infecções por HIV , Humanos , Infecções por HIV/epidemiologia , Infecções por HIV/etnologia , Infecções por HIV/prevenção & controle , Estados Unidos/epidemiologia , COVID-19/epidemiologia , SARS-CoV-2 , Disparidades em Assistência à Saúde , Racismo Sistêmico , Disparidades nos Níveis de Saúde , Epidemias , RacismoRESUMO
Individually, the COVID-19 and HIV pandemics have differentially impacted minoritized groups due to the role of social determinants of health (SDoH) in the U.S. Little is known how the collision of these two pandemics may have exacerbated adverse health outcomes. We evaluated county-level SDoH and associations with hospitalization after a COVID-19 diagnosis among people with (PWH) and without HIV (PWOH) by racial/ethnic groups. We used the U.S. National COVID Cohort Collaborative (January 2020-November 2023), a nationally-sampled electronic health record repository, to identify adults who were diagnosed with COVID-19 with HIV (n = 22,491) and without HIV (n = 2,220,660). We aggregated SDoH measures at the county-level and categorized racial/ethnic groups as Non-Hispanic (NH) White, NH-Black, Hispanic/Latinx, NH-Asian and Pacific Islander (AAPI), and NH-American Indian or Alaskan Native (AIAN). To estimate associations of county-level SDoH with hospitalization after a COVID-19 diagnosis, we used multilevel, multivariable logistic regressions, calculating adjusted relative risks (aRR) with 95% confidence intervals (95% CI). COVID-19 related hospitalization occurred among 11% of PWH and 7% of PWOH, with the highest proportion among NH-Black PWH (15%). In evaluating county-level SDoH among PWH, we found higher average household size was associated with lower risk of COVID-19 related hospitalization across racial/ethnic groups. Higher mean commute time (aRR: 1.76; 95% CI 1.10-2.62) and higher proportion of adults without health insurance (aRR: 1.40; 95% CI 1.04-1.84) was associated with a higher risk of COVID-19 hospitalization among NH-Black PWH, however, NH-Black PWOH did not demonstrate these associations. Differences by race and ethnicity exist in associations of adverse county-level SDoH with COVID-19 outcomes among people with and without HIV in the U.S.
Assuntos
COVID-19 , Infecções por HIV , Hospitalização , Determinantes Sociais da Saúde , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , COVID-19/epidemiologia , COVID-19/etnologia , Etnicidade , Disparidades nos Níveis de Saúde , Infecções por HIV/epidemiologia , Infecções por HIV/etnologia , Hospitalização/estatística & dados numéricos , Estudos Retrospectivos , Fatores Socioeconômicos , Estados Unidos/epidemiologia , Grupos RaciaisRESUMO
Potential associations between periconception dolutegravir (DTG) exposure and neural tube defects (NTDs) reported in 2018 caused shifting international and national antiretroviral treatment (ART) guidelines. They sometimes required women to use contraception prior to initiating DTG. To better understand the tensions between ART and family planning (FP) choices, and explore the decision-making processes of women living with HIV (WLHIV) and their healthcare providers (HCPs) employed, we conducted interviews with WLHIV exposed to DTG and their providers in western Kenya from July 2019 to August 2020. For the interviews with WLHIV, we sampled women at varying ages who either continued using DTG, switched to a different ART, or became pregnant while using DTG. We utilized inductive coding and thematic analysis. We conducted 44 interviews with WLHIV and 10 with providers. We found four dominant themes: (1) a range of attitudes about birth defects, (2) nuanced knowledge of DTG and its potential risk of birth defects, (3) significant tensions at the intersection of DTG and FP use with varying priorities amongst WLHIV and their providers for navigating the tensions, and (4) WLHIV desiring autonomy, and provider support for this, in such decision-making. Variations in beliefs were noted between WLHIV and HCPs. WLHIV highlighted the impact of community and social beliefs when discussing their attitudes while HCPs generally reported more medicalized views towards DTG utilization, potential adverse outcomes, and FP selection. Decisions pertaining to ART and FP selection are complex, and HIV treatment guidelines need to better support women's agency and reproductive health justice.
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Infecções por HIV , Compostos Heterocíclicos com 3 Anéis , Oxazinas , Piperazinas , Piridonas , Pesquisa Qualitativa , Humanos , Feminino , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/psicologia , Adulto , Gravidez , Quênia/epidemiologia , Serviços de Planejamento Familiar , Defeitos do Tubo Neural , Conhecimentos, Atitudes e Prática em Saúde , Saúde Reprodutiva , Entrevistas como Assunto , Adulto Jovem , Tomada de Decisões , Fármacos Anti-HIV/uso terapêutico , AnticoncepçãoRESUMO
To exploratorily test (1) the impact of HIV and aging process among PLWH on COVID-19 outcomes; and (2) whether the effects of HIV on COVID-19 outcomes differed by immunity level. The data used in this study was retrieved from the COVID-19 positive cohort in National COVID Cohort Collaborative (N3C). Multivariable logistic regression models were conducted on populations that were matched using either exact matching or propensity score matching (PSM) with varying age difference between PLWH and non-PLWH to examine the impact of HIV and aging process on all-cause mortality and hospitalization among COVID-19 patients. Subgroup analyses by CD4 counts and viral load (VL) levels were conducted using similar approaches. Among the 2,422,864 adults with a COVID-19 diagnosis, 15,188 were PLWH. PLWH had a significantly higher odds of death compared to non-PLWH until age difference reached 6 years or more, while PLWH were still at an elevated risk of hospitalization across all matched cohorts. The odds of both severe outcomes were persistently higher among PLWH with CD4 < 200 cells/mm3. VL ≥ 200 copies/ml was only associated with higher hospitalization, regardless of the predefined age differences. Age advancement in HIV might significantly contribute to the higher risk of COVID-19 mortality and HIV infection may still impact COVID-19 hospitalization independent of the age advancement in HIV.
RESUMO
BACKGROUND: Pregnant women and children living with HIV in Kenya achieve viral suppression (VS) at lower rates than other adults. While many factors contribute to these low rates, the acquisition and development of HIV drug resistance mutations (DRMs) are a contributing factor. Recognizing the significance of DRMs in treatment decisions, resource-limited settings are scaling up national DRM testing programs. From provider and patient perspectives, however, optimal ways to operationalize and scale-up DRM testing in such settings remain unclear. METHODS: Our mixed methods study evaluates the attitudes towards, facilitators to, and barriers to DRM testing approaches among children and pregnant women on antiretroviral therapy (ART) in five HIV treatment facilities in Kenya. We conducted 68 key informant interviews (KIIs) from December 2019 to December 2020 with adolescents, caregivers, pregnant women newly initiating ART or with a high viral load, and providers, laboratory/facility leadership, and policy makers. Our KII guides covered the following domains: (1) DRM testing experiences in routine care and through our intervention and (2) barriers and facilitators to routine and point-of-care DRM testing scale-up. We used inductive coding and thematic analysis to identify dominant themes with convergent and divergent subthemes. RESULTS: The following themes emerged from our analysis: (1) DRM testing and counseling were valuable to clinical decision-making and reassuring to patients, with timely results allowing providers to change patient ART regimens faster; (2) providers and policymakers desired an amended and potentially decentralized DRM testing process that incorporates quicker sample-to-results turn-around-time, less burdensome procedures, and greater patient and provider "empowerment" to increase comfort with testing protocols; (3) facility-level delays, deriving from overworked facilities and sample tracking difficulties, were highlighted as areas for improvement. CONCLUSIONS: DRM testing has the potential to considerably improve patient health outcomes. Key informants recognized several obstacles to implementation and desired a more simplified, time-efficient, and potentially decentralized DRM testing process that builds provider comfort and confidence with DRM testing protocols. Further investigating the implementation, endurance, and effectiveness of DRM testing training is critical to addressing the barriers and areas of improvement highlighted in our study. TRIAL REGISTRATION: NCT03820323.
Assuntos
Emoções , Gestantes , Adolescente , Adulto , Criança , Feminino , Humanos , Gravidez , Teste de HIV , QuêniaRESUMO
BACKGROUND: The transition to dolutegravir-containing antiretroviral therapy (ART) in low- and middle-income countries (LMICs) was complicated by an initial safety signal in May 2018 suggesting that exposure to dolutegravir at conception was possibly associated with infant neural tube defects. On the basis of additional evidence, in July 2019, the World Health Organization recommended dolutegravir for all adults and adolescents living with HIV. OBJECTIVE: To describe dolutegravir uptake and disparities by sex and age group in LMICs. DESIGN: Observational cohort study. SETTING: 87 sites that began using dolutegravir in 11 LMICs in the Asia-Pacific; Caribbean, Central and South America network for HIV epidemiology (CCASAnet); and sub-Saharan African regions of the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. PATIENTS: 134 672 patients aged 16 years or older who received HIV care from January 2017 through March 2020. MEASUREMENTS: Sex, age group, and dolutegravir uptake (that is, newly initiating ART with dolutegravir or switching to dolutegravir from another regimen). RESULTS: Differences in dolutegravir uptake among females of reproductive age (16 to 49 years) emerged after the safety signal. By the end of follow-up, the cumulative incidence of dolutegravir uptake among females 16 to 49 years old was 29.4% (95% CI, 29.0% to 29.7%) compared with 57.7% (CI, 57.2% to 58.3%) among males 16 to 49 years old. This disparity was greater in countries that began implementing dolutegravir before the safety signal and initially had highly restrictive policies versus countries with a later rollout. Dolutegravir uptake was similar among females and males aged 50 years or older. LIMITATION: Follow-up was limited to 6 to 8 months after international guidelines recommended expanding access to dolutegravir. CONCLUSION: Substantial disparities in dolutegravir uptake affecting females of reproductive age through early 2020 are documented. Although this disparity was anticipated because of country-level restrictions on access, the results highlight its extent and initial persistence. PRIMARY FUNDING SOURCE: National Institutes of Health.
Assuntos
Países em Desenvolvimento , Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/administração & dosagem , Inibidores de Integrase de HIV/efeitos adversos , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Oxazinas/administração & dosagem , Oxazinas/efeitos adversos , Piperazinas/administração & dosagem , Piperazinas/efeitos adversos , Piridonas/administração & dosagem , Piridonas/efeitos adversos , Adolescente , Adulto , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Accurate diagnosis of coronavirus disease 2019 is essential to limiting transmission within healthcare settings. The aim of this study was to identify patient demographic and clinical characteristics that could impact the clinical sensitivity of the nasopharyngeal severe acute respiratory syndrome coronavirus-2 (SARS-CoV2) reverse transcription polymerase chain reaction (RT-PCR) test. METHODS: We conducted a retrospective, matched case-control study of patients who underwent repeated nasopharyngeal SARS-CoV2 RT-PCR testing at a tertiary care academic medical center between March 1 and July 23, 2020. The primary endpoint was conversion from negative to positive PCR status within 14 days. We conducted conditional logistic regression modeling to assess the associations between demographic and clinical features and conversion to test positivity. RESULTS: Of 51,116 patients with conclusive SARS-CoV2 nasopharyngeal RT-PCR results, 97 patients converted from negative to positive within 14 days. We matched those patients 1:2 to 194 controls by initial test date. In multivariate analysis, clinical suspicion for a respiratory infection (adjusted odds ratio [aOR] 20.9, 95% confidence interval [CI]: 3.1-141.2) and lack of pulmonary imaging (aOR 4.7, 95% CI: 1.03-21.8) were associated with conversion, while a lower burden of comorbidities trended toward an increased odds of conversion (aOR 2.2, 95% CI: 0.9-5.3). CONCLUSIONS: Symptoms consistent with a respiratory infection, especially in relatively healthy individuals, should raise concerns about a clinical false-negative result. We have identified several characteristics that should be considered when creating institutional infection prevention guidelines in the absence of more definitive data and should be included in future studies.
Assuntos
COVID-19 , SARS-CoV-2 , COVID-19/diagnóstico , Teste para COVID-19 , Estudos de Casos e Controles , Humanos , Reação em Cadeia da Polimerase , RNA Viral , Estudos Retrospectivos , SARS-CoV-2/genéticaRESUMO
African immigrants are disproportionately affected by HIV compared to U.S.-born individuals, and early HIV testing is the key challenge in ending the HIV epidemic in these communities. HIV-related stigma appears to be the most significant barrier to testing for HIV among African communities in King County, WA. In this formative study, we conducted thirty key informant interviews and five focus group discussions (n = total 72 participants) with Ethiopian, Somali, and Eritrean people living with HIV, health professionals, religious and other community leaders, and lay community members in King County to better understand HIV-related and intersectional stigmas' impact on HIV testing behaviors. We used inductive coding and thematic analysis. Participants from all communities reported similar themes for HIV-related and intersectional stigmas' influences on HIV testing behaviors. Misconceptions or poor messaging, e.g., regarding treatability of HIV, as well as normative or religious/moral beliefs around pre/extramarital sex contributed to HIV-related stigma. Intersecting identities such as immigrant status, race/ethnicity, and having a non-English language preference, all intermingle to further influence access to the U.S. healthcare system, including for HIV testing. These findings can be used to inform future research on community-led approaches to addressing early HIV testing amongst African immigrant communities.
RESUMEN: Los inmigrantes africanos son afectados por el VIH de manera desproporcionada en comparación con individuos nacidos en E.E.U.U. y el testeo temprano de VIH es el desafío clave para parar la epidemia de VIH en estas comunidades. El estigma relacionado con el VIH parecería ser la barrera más importante al testeo temprano de VIH entre las comunidades africanas en el condado de King, Washington. En este estudio formativo hemos realizado treinta entrevistas con informantes clave y cinco grupos de discusión (n = 72 participantes totales) con participantes etíopes, somalíes, y eritreos viviendo con el VIH, profesionales de la salud, líderes religiosos y de la comunidad, y otros miembros de la comunidad en el condado King para desarrollar un mejor conocimiento de los estigmas interseccionales y relacionados con el VIH. Usamos métodos de codificación inductiva y análisis temático. Participantes de todas las comunidades reportaron temas similares al describir como los estigmas interseccionales y relacionados con el VIH influyen en los comportamientos de acceso a pruebas de VIH. Malentendidos o mensajes inadecuados, por ejemplo, sobre la tratabilidad del VIH y las creencias normativas o religiosas/morales entorno al sexo pre/extramarital, contribuyeron al estigma relacionado con el VIH. Las identidades que se intersecan, como el estatus migratorio, raza/etnia, y no hablar inglés como lenguaje preferido, se entremezclan para influir de mayor manera el acceso al sistema de salud estadounidense, incluyendo para las pruebas de VIH. Estos hallazgos pueden ser usados para informar futuros proyectos de investigación sobre estrategias lideradas por la comunidad para abordar el diagnóstico temprano de VIH en la comunidad de inmigrantes africanos.
Assuntos
Emigrantes e Imigrantes , Infecções por HIV , Infecções por HIV/diagnóstico , Infecções por HIV/prevenção & controle , Teste de HIV , Humanos , Estigma Social , Washington/epidemiologiaRESUMO
BACKGROUND: Viral suppression (VS) is a marker of effective HIV therapy, and viral load (VL) testing is critical for treatment monitoring, especially in high-risk groups such as children and pregnant/postpartum women. Although routine VL testing, via centralized laboratory networks, was implemented in Kenya starting in 2014, optimization and sustainable scale up of VL testing are still needed. METHODS: We conducted a mixed methods study to evaluate the impact of higher frequency, point-of-care (POC) VL testing in optimizing VS among children and pregnant/postpartum women on antiretroviral treatment (ART) in five HIV treatment facilities in western Kenya in the Opt4Kids and Opt4Mamas studies. We conducted 68 key informant interviews (KIIs) from December 2019 to December 2020 with children and pregnant women living with HIV, child caregivers, providers, laboratory/facility leadership, and county- or national-level policymakers. Our KII guide covered the following domains: (1) barriers and facilitators to ART use and VS, (2) literacy and experiences with VL in routine care and via study, and (3) opinions on how to scale up VL testing for optimal programmatic use. We used inductive coding and thematic analysis to identify dominant themes with convergent and divergent subthemes. RESULTS: Three main themes regarding VL testing emerged from our analysis. (1) Key informants uniformly contrasted POC VL testing's faster results turnaround, higher accessibility, and likely cost-effectiveness against centralized VL testing. (2) Key informants also identified areas of improvement for POC VL testing in Kenya, such as quality control, human resource and infrastructure capacity, supply chain management, and integration of VL testing systems. (3) To enable successful scale-up of VL testing, key informants proposed expanding the POC VL testing scheme, electronic medical records systems, conducting quality checks locally, capacity building and developing strong partnerships between key stakeholders. CONCLUSION: The more accessible, decentralized model of POC VL testing was deemed capable of overcoming critical challenges associated with centralized VL testing and was considered highly desirable for optimizing VS for children and pregnant/postpartum women living with HIV. While POC VL testing has the potential to improve VS rates among these populations, additional research is needed to develop strategies for ensuring the sustainability of POC VL testing programs. TRIAL REGISTRATION: NCT03820323, 29/01/2019.
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Fármacos Anti-HIV , Infecções por HIV , Criança , Feminino , Humanos , Gravidez , Fármacos Anti-HIV/uso terapêutico , Antirretrovirais/uso terapêutico , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Quênia , Sistemas Automatizados de Assistência Junto ao Leito , Testes Imediatos , Carga ViralRESUMO
BACKGROUND: Preventing unintended pregnancies is paramount for women living with HIV (WLHIV). Previous studies have suggested that efavirenz-containing antiretroviral therapy (ART) reduces contraceptive effectiveness of implants, but there are uncertainties regarding the quality of the electronic medical record (EMR) data used in these prior studies. METHODS: We conducted a retrospective, cohort study of EMR data from 2011 to 2015 among WLHIV of reproductive age accessing HIV care in public facilities in western Kenya. We validated a large subsample of records with manual chart review and telephone interviews. We estimated adjusted incidence rate ratios (aIRRs) with Poisson regression accounting for the validation sampling using inverse probability weighting and generalized raking. RESULTS: A total of 85,324 women contributed a total of 170,845 women-years (w-y) of observation time; a subset of 5080 women had their charts reviewed, and 1285 underwent interviews. Among implant users, the aIRR of pregnancy for efavirenz- vs. nevirapine-containing ART was 1.9 (95% CI 1.6, 2.4) using EMR data only and 3.2 (95% CI 1.8, 5.7) when additionally using both chart review and interview validated data. Among efavirenz users, the aIRR of pregnancy for depomedroxyprogesterone acetate (DMPA) vs. implant use was 1.8 (95% CI 1.5, 2.1) in EMR only and 2.4 (95% CI 1.0, 6.1) using validated data. CONCLUSION: Pregnancy rates are higher when contraceptive implants are concomitantly used with efavirenz-containing ART, though rates were similar to leading alternative contraceptive methods such as DMPA. Our data provides policymakers, program staff, and WLHIV greater confidence in guiding their decision-making around contraceptive and ART options. Our novel, 3-phase validation sampling provides an innovative tool for using routine EMR data to improve the robustness of data quality.
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Anticoncepcionais , Infecções por HIV , Estudos de Coortes , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Quênia/epidemiologia , Gravidez , Estudos RetrospectivosRESUMO
With the planned scale-up of pre-exposure prophylaxis (PrEP) for HIV prevention among serodiscordant couples in resource-limited settings, gaining an understanding of what motivates serodiscordant couples to prevent HIV is critical. We conducted 44 semi-structured, in-depth individual or couple interviews with 63 participants (33 HIV-infected and 30 HIV-uninfected participants) enrolled in a prospective implementation study of oral antiretroviral-based prevention in Kisumu, Kenya. Transcripts were iteratively analysed using inductive content analysis. Findings point to the importance of maintaining the emotional and economic stability of the partnership and family as motivators in preventing HIV transmission. Female participants identified fear of blame or potential violence for transmitting HIV as a motivator. Furthermore, couples primarily held the HIV-infected individual responsible for HIV prevention, but also held women more accountable for the use of prevention methods such as condoms. These themes substantiate traditional gender norms but also reveal how dyadic interdependence challenges these norms. As programmes in resource-limited settings scale up PrEP access, they should simultaneously capitalise on HIV serodiscordant couples' motivations for HIV prevention and address gender norms so women do not find themselves unduly responsible for the prevention of HIV transmission.
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Infecções por HIV/prevenção & controle , Soropositividade para HIV , Motivação , Profilaxia Pré-Exposição/métodos , Parceiros Sexuais/psicologia , Adulto , Fármacos Anti-HIV/uso terapêutico , Características da Família , Feminino , Humanos , Entrevistas como Assunto , Quênia , Masculino , Estudos ProspectivosRESUMO
Background: Genital human immunodeficiency virus (HIV) RNA shedding can continue despite HIV being undetectable in blood, and can be associated with transmission. Methods: We included African women on antiretroviral therapy (ART). Linear and generalized linear mixed models were used to compare the magnitude and prevalence of genital shedding, respectively, by time since ART initiation. Multivariable logistic regression with generalized estimating equations was used to assess predictors of genital shedding among women with undetectable plasma viral load (VL). Results: Among 1114 women, 5.8% of visits with undetectable plasma VL and 23.6% of visits with detectable VL had genital shedding. The proportion of visits with genital shedding decreased with time since ART initiation but the magnitude of shedding remained unchanged when plasma VL was undetectable (P = .032). Prevalence of shedding did not vary by time since ART initiation when plasma VL was detectable (P = .195), though the magnitude of shedding significantly increased (P = .04). Predictors of genital shedding were HIV disease stage, antiretroviral regimen, and genital ulcers or cervical tenderness. Discussion: In addition to ART, reducing immune activation through prevention and treatment of HIV-related conditions and genital tract infections may decrease the risk of HIV-1 shedding and potential transmission.
Assuntos
Antirretrovirais/uso terapêutico , Genitália Feminina/virologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/isolamento & purificação , Eliminação de Partículas Virais , Adulto , África/epidemiologia , Sangue/virologia , Feminino , Humanos , Prevalência , Estudos Prospectivos , Carga ViralRESUMO
BACKGROUND: Factors influencing fertility desires among HIV-infected individuals remain poorly understood. With new recommendations for universal HIV treatment and increasing antiretroviral therapy (ART) access, we sought to evaluate how access to early ART influences fertility desires among HIV-infected ART-naïve women. METHODS: Semi-structured in-depth interviews were conducted with a select subgroup of 20 HIV-infected ART-naïve women attending one of 13 HIV facilities in western Kenya between July and August 2014 who would soon newly become eligible to initiate ART based on the latest national policy recommendations. The interviews covered four major themes: 1) definitions of family and children's role in community; 2) personal, interpersonal, institutional, and societal factors influencing fertility desires; 3) influence of HIV-positive status on fertility desires; and 4) influence of future ART initiation on fertility desires. An iterative process of reading transcripts, applying inductive codes, and comparing and contrasting codes was used to identify convergent and divergent themes. RESULTS: The women indicated their HIV-positive status did influence-largely negatively-their fertility desires. Furthermore, initiating ART and anticipating improved health status did not necessarily translate to increased fertility desires. Instead, individual factors, such as age, parity, current health status, financial resources and number of surviving or HIV-infected children, played a crucial role in decisions about future fertility. In addition, societal influences, such as community norms and health providers' expectations of their fertility desires, played an equally important role in determining fertility desires. CONCLUSIONS: Initiating ART may not be the leading factor influencing fertility desires among previously ART-naïve HIV-infected women. Instead, individual and societal factors appear to be the major determinants of fertility desires among these women.
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Serviços de Planejamento Familiar , Infecções por HIV/psicologia , Mulheres/psicologia , Adulto , Antirretrovirais/uso terapêutico , Atitude do Pessoal de Saúde , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Pesquisa Qualitativa , Fatores SocioeconômicosRESUMO
Background: Levonorgestrel implant is a highly effective hormonal contraceptive, but its efficacy may be compromised when used with cytochrome enzyme inducers such as efavirenz. The primary aim of this study was to evaluate methods of mitigating the drug interaction. Methods: Using a physiologically-based pharmacokinetic (PBPK) model for levonorgestrel that we developed within the Simcyp® program, we evaluated a higher dose of levonorgestrel implant, a lower dose of efavirenz, and the combination of both, as possible methods to mitigate the interaction. In addition, we investigated the impact on levonorgestrel total and unbound concentrations of other events likely to be associated with efavirenz coadministration: changes in plasma protein binding of levonorgestrel (as with displacement) and high variability of efavirenz exposure (as with genetic polymorphism of its metabolism). The range of fraction unbound tested was 0.6% to 2.6%, and the range of efavirenz exposure ranged from the equivalent of 200 mg to 4800 mg doses. Results: Levonorgestrel plasma concentrations at any given time with a standard 150 mg implant dose are predicted to be approximately 68% of those of control when given with efavirenz 600 mg and 72% of control with efavirenz 400 mg. With double-dose levonorgestrel, the predictions are 136% and 145% of control, respectively. A decrease in levonorgestrel plasma protein binding is predicted to primarily decrease total levonorgestrel plasma concentrations, whereas higher efavirenz exposure is predicted to decrease total and unbound concentrations. Conclusions: Simulations suggest that doubling the dose of levonorgestrel, particularly in combination with 400 mg daily efavirenz, may mitigate the drug interaction. Changes in levonorgestrel plasma protein binding and efavirenz genetic polymorphism may help explain differences between model predictions and clinical data but need to be studied further.
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Postpartum depression (PPD) is a mood disorder affecting one in seven women after childbirth that is often under-screened and under-detected. If not diagnosed and treated, PPD is associated with long-term developmental challenges in the child and maternal morbidity. Wearable technologies, such as smartwatches and fitness trackers (e.g., Fitbit), offer continuous and longitudinal digital phenotyping for mood disorder diagnosis and monitoring, with device wear time being an important yet understudied aspect. Using the All of Us Research Program (AoURP) dataset, we assessed the percentage of days women with PPD wore Fitbit devices across pre-pregnancy, pregnancy, postpartum, and PPD periods, as determined by electronic health records. Wear time was compared in women with and without PPD using linear regression models. Results showed a strong trend that women in the PPD cohort wore their Fitbits more those without PPD during the postpartum (PPD: mean=72.9%, SE=13.8%; non-PPD: mean=58.9%, SE=12.2%, P-value=0.09) and PPD time periods (PPD: mean=70.7%, SE=14.5%; non-PPD: mean=55.6%, SE=12.9%, P-value=0.08). We hypothesize this may be attributed to hypervigilance, given the common co-occurrence of anxiety symptoms among women with PPD. Future studies should assess the link between PPD, hypervigilance, and wear time patterns. We envision that device wear patterns with digital biomarkers like sleep and physical activity could enhance early PPD detection using machine learning by alerting clinicians to potential concerns facilitating timely screenings, which may have implications for other mental health disorders.
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OBJECTIVE: Autoimmune or inflammatory rheumatic diseases (AIRDs) increase the risk for poor COVID-19 outcomes. Although rurality is associated with higher post-COVID-19 mortality in the general population, whether rurality elevates this risk among people with AIRD is unknown. We assessed associations between rurality and post-COVID-19 all-cause mortality, up to two years post infection, among people with AIRD using a large nationally sampled US cohort. METHODS: This retrospective study used the National COVID Cohort Collaborative, a medical records repository containing COVID-19 patient data. We included adults with two or more AIRD diagnostic codes and a COVID-19 diagnosis documented between April 2020 and March 2023. Rural residency was categorized using patient residential zip codes. We adjusted for AIRD medications and glucocorticoid prescription, age, sex, race and ethnicity, tobacco or substance use, comorbid burden, and SARS-CoV-2 variant-dominant periods. Multivariable Cox proportional hazards with inverse probability treatment weighting assessed associations between rurality and two-year all-cause mortality. RESULTS: Among the 86,467 SARS-CoV-2-infected persons with AIRD, we observed a higher risk for two-year post-COVID-19 mortality in rural versus urban dwellers. Rural-residing persons with AIRD had higher two-year all-cause mortality risk (adjusted hazard ratio 1.24, 95% confidence interval 1.19-1.29). Glucocorticoid, immunosuppressive, and rituximab prescriptions were associated with a higher risk for two-year post-COVID-19 mortality, whereas risk with nonbiologic or biologic disease-modifying antirheumatic drugs was lower. CONCLUSION: Rural residence in people with AIRD was independently associated with higher two-year post-COVID-19 mortality in a large US cohort after adjusting for background risk factors. Policymakers and health care providers should consider these findings when designing interventions to improve outcomes in people with AIRD following SARS-CoV-2 infection, especially among high-risk rural residents.
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BACKGROUND: Postpartum depression (PPD) poses a significant maternal health challenge. The current approach to detecting PPD relies on in-person postpartum visits, which contributes to underdiagnosis. Furthermore, recognizing PPD symptoms can be challenging. Therefore, we explored the potential of using digital biomarkers from consumer wearables for PPD recognition. OBJECTIVE: The main goal of this study was to showcase the viability of using machine learning (ML) and digital biomarkers related to heart rate, physical activity, and energy expenditure derived from consumer-grade wearables for the recognition of PPD. METHODS: Using the All of Us Research Program Registered Tier v6 data set, we performed computational phenotyping of women with and without PPD following childbirth. Intraindividual ML models were developed using digital biomarkers from Fitbit to discern between prepregnancy, pregnancy, postpartum without depression, and postpartum with depression (ie, PPD diagnosis) periods. Models were built using generalized linear models, random forest, support vector machine, and k-nearest neighbor algorithms and evaluated using the κ statistic and multiclass area under the receiver operating characteristic curve (mAUC) to determine the algorithm with the best performance. The specificity of our individualized ML approach was confirmed in a cohort of women who gave birth and did not experience PPD. Moreover, we assessed the impact of a previous history of depression on model performance. We determined the variable importance for predicting the PPD period using Shapley additive explanations and confirmed the results using a permutation approach. Finally, we compared our individualized ML methodology against a traditional cohort-based ML model for PPD recognition and compared model performance using sensitivity, specificity, precision, recall, and F1-score. RESULTS: Patient cohorts of women with valid Fitbit data who gave birth included <20 with PPD and 39 without PPD. Our results demonstrated that intraindividual models using digital biomarkers discerned among prepregnancy, pregnancy, postpartum without depression, and postpartum with depression (ie, PPD diagnosis) periods, with random forest (mAUC=0.85; κ=0.80) models outperforming generalized linear models (mAUC=0.82; κ=0.74), support vector machine (mAUC=0.75; κ=0.72), and k-nearest neighbor (mAUC=0.74; κ=0.62). Model performance decreased in women without PPD, illustrating the method's specificity. Previous depression history did not impact the efficacy of the model for PPD recognition. Moreover, we found that the most predictive biomarker of PPD was calories burned during the basal metabolic rate. Finally, individualized models surpassed the performance of a conventional cohort-based model for PPD detection. CONCLUSIONS: This research establishes consumer wearables as a promising tool for PPD identification and highlights personalized ML approaches, which could transform early disease detection strategies.