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BACKGROUND: More efficient methods to detect and treat precancerous lesions of the cervix at a single visit, such as low-cost confocal microscopy, could improve early diagnosis and hence outcomes. We piloted a prototype smartphone-compatible confocal micro-endoscope (SCME) among women presenting to a public cervical cancer screening clinic in Kampala, Uganda. We describe the piloting of the SCME device at an urban clinic used by lower cadre staff. METHODS: We screened women aged 18 and 60 years, who presented for cervical cancer screening at the Kawempe National Referral Hospital Kampala, and evaluated the experience of their providers (nurses). Nurses received a 2-day training by the study doctors on how to use the SCME, which was added to the standard Visual Inspection with Acetic acid (VIA)-based cervical cancer screening. The SCME was used to take colposcopy images before and after VIA at positions 12 and 6 O'clock if VIA negative, and on precancer-suspicious lesions if VIA positive. We used questionnaires to assess the women's experiences after screening, and the experience of the nurses who operated the SCME. RESULTS: Between November 2021 and July 2022, we screened 291 women with a median age of 36 years and 65.7% were HIV positive. Of the women screened, 146 were eligible for VIA, 123 were screened with the SCME, and we obtained confocal images from 103 women. Of those screened with the SCME, 60% found it comfortable and 81% were willing to screen again with it. Confocal images from 79% of the women showed distinguishable cellular features, while images from the remaining 21% were challenging to analyze. Nurses reported a mean score of 85% regarding the SCME's usefulness to their work, 71% regarding their satisfaction and willingness to use it again, 63% in terms of ease of use, and 57% concerning the ease of learning how to operate the SCME. CONCLUSION: Our findings demonstrate the feasibility of using the SCME by lower cadre staff in low-resource settings to aid diagnosis of precancerous lesions. However, more work is needed to make it easier for providers to learn how to operate the SCME and capture high-quality confocal images.
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Colposcopía , Detección Precoz del Cáncer , Microscopía Confocal , Teléfono Inteligente , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/diagnóstico , Adulto , Detección Precoz del Cáncer/métodos , Uganda , Persona de Mediana Edad , Microscopía Confocal/métodos , Colposcopía/métodos , Adulto Joven , Adolescente , Proyectos Piloto , Configuración de Recursos LimitadosRESUMEN
Immunohistochemical (IHC) staining for the antigen of Kaposi sarcoma-associated herpesvirus (KSHV), latency-associated nuclear antigen (LANA), is helpful in diagnosing Kaposi sarcoma (KS). A challenge, however, lies in distinguishing anti-LANA-positive cells from morphologically similar brown counterparts. In this work, we demonstrate a framework for automated localization and quantification of LANA positivity in whole slide images (WSI) of skin biopsies, leveraging weakly supervised multiple instance learning (MIL) while reducing false positive predictions by introducing a novel morphology-based slide aggregation method. Our framework generates interpretable heatmaps, offering insights into precise anti-LANA-positive cell localization within WSIs and a quantitative value for the percentage of positive tiles, which may assist with histological subtyping. We trained and tested our framework with an anti-LANA-stained KS pathology dataset prepared by pathologists in the United States from skin biopsies of KS-suspected patients investigated in Uganda. We achieved an area under the receiver operating characteristic curve (AUC) of 0.99 with a sensitivity and specificity of 98.15% and 96.00% in predicting anti-LANA-positive WSIs in a test dataset. We believe that the framework can provide promise for automated detection of LANA in skin biopsies, which may be especially impactful in resource-limited areas that lack trained pathologists.
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BACKGROUND: The HIV care cascade is a framework to examine effectiveness of HIV programs and progress toward global targets to end the epidemic but has been conceptualized as a unidirectional process that ignores cyclical care patterns. We present a dynamic cascade that accounts for patient "churn" and apply novel analytic techniques to readily available clinical data to robustly estimate program outcomes and efficiently assess progress toward global targets. METHODS: Data were assessed for 35,649 people living with HIV and receiving care at 78 clinics in East Africa between 2014 and 2020. Patients were aged ≥15 years and had ≥1 viral load measurements. We used multi-state models to estimate the probability of being in 1 of 5 states of a dynamic HIV cascade: (1) in HIV care but not on antiretroviral therapy (ART), (2) on ART, (3) virally suppressed, (4) in a gap-in-care, and (5) deceased and compared these among subgroups. To assess progress toward global targets, we summed those probabilities across patients and generated population-level proportions of patients on ART and virally suppressed in mid-2020. RESULTS: One year after enrollment, 2.8% of patients had not initiated ART, 86.7% were receiving ART, 57.4% were virally suppressed, 10.2% were disengaged from care, and 0.3% had died. At 5 years, the proportion on ART remained steady but viral suppression increased to 77.2%. Of those aged 15-25, >20% had disengaged from care and <60% were virally suppressed. In mid-2020, 90.1% of the cohort was on ART, 90.7% of whom had suppressed virus. CONCLUSIONS: Novel analytic approaches can characterize patient movement through a dynamic HIV cascade and, importantly, by capitalizing on readily available data from clinical cohorts, offer an efficient approach to estimate population-level proportions of patients on ART and virally suppressed. Significant progress toward global targets was observed in our cohort but challenges remain among younger patients.
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Infecciones por VIH , Carga Viral , Humanos , Infecciones por VIH/tratamiento farmacológico , Adulto , Femenino , Masculino , Adulto Joven , Persona de Mediana Edad , Adolescente , Fármacos Anti-VIH/uso terapéutico , África Oriental/epidemiología , Política de SaludRESUMEN
Persons with HIV-associated Kaposi's sarcoma (KS) experience three co-existing stigmatizing health conditions: skin disease, HIV, and cancer, which contribute to a complex experience of stigmatization and to delays in diagnosis and treatment. Despite the importance of stigma among these patients, there are few proven stigma-reduction strategies for HIV-associated malignancies. Using qualitative methods, we explore how people with HIV-associated KS in western Kenya between August 2022 and 2023 describe changes in their stigma experience after participation in a multicomponent navigation strategy, which included 1) physical navigation and care coordination, 2) video-based education with motivational survivor stories, 3) travel stipend, 4) health insurance enrollment assistance, 5) health insurance stipend, and 6) peer mentorship. A purposive sample of persons at different stages of chemotherapy treatment were invited to participate. Participants described how a multicomponent navigation strategy contributed to increased knowledge and awareness, a sense of belonging, hope to survive, encouragement, and social support, which served as stigma mitigators, likely counteracting the major drivers of intersectional stigma in HIV-associated KS.
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Infecciones por VIH , Investigación Cualitativa , Sarcoma de Kaposi , Estigma Social , Humanos , Sarcoma de Kaposi/psicología , Sarcoma de Kaposi/terapia , Sarcoma de Kaposi/etiología , Sarcoma de Kaposi/epidemiología , Infecciones por VIH/psicología , Infecciones por VIH/complicaciones , Kenia/epidemiología , Masculino , Femenino , Adulto , Persona de Mediana Edad , Navegación de PacientesRESUMEN
BACKGROUND: Monitoring and evaluation of clinical programs requires assessing patient outcomes. Numerous challenges complicate these efforts, the most insidious of which is loss to follow-up (LTFU). LTFU is a composite outcome, including individuals out of care, undocumented transfers, and unreported deaths. Incorporation of vital status information from routine patient outreach may improve the mortality estimates for those LTFU. SETTINGS: We analyzed routinely collected clinical and patient tracing data for individuals (15 years or older) initiating antiretroviral treatment between January 2014 and December 2018 at 2 public HIV care clinics in greater Rakai, Uganda. METHODS: We derived unadjusted mortality estimates using Kaplan-Meier methods. Estimates, adjusted for unreported deaths, applied weighting through the Frangakis and Rubin method to represent outcomes among LTFU patients who were successfully traced and for whom vital status was ascertained. Confidence intervals were determined through bootstrap methods. RESULTS: Of 1969 patients with median age at antiretroviral treatment initiation of 31 years (interquartile range: 25-38), 1126 (57.2%) were female patients and 808 (41%) were lost. Of the lost patients, 640 patient files (79.2%) were found and reviewed, of which 204 (31.8%) had a tracing attempt. Within the electronic health records of the program, 28 deaths were identified with an estimated unadjusted mortality 1 year after antiretroviral treatment initiation of 2.5% (95% CI: 1.8% to 3.3%). Using chart review and patient tracing data, an additional 24 deaths (total 52) were discovered with an adjusted 1-year mortality of 3.8% (95% CI: 2.6% to 5.0%). CONCLUSIONS: Data from routine outreach efforts by HIV care and treatment programs can be used to support plausible adjustments to estimates of client mortality. Mortality estimates without active ascertainment of vital status of LTFU patients may significantly underestimate program mortality.
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Fármacos Anti-VIH , Infecciones por VIH , Adulto , Humanos , Femenino , Masculino , Infecciones por VIH/tratamiento farmacológico , Fármacos Anti-VIH/uso terapéutico , Uganda/epidemiología , Perdida de Seguimiento , Antirretrovirales/uso terapéuticoRESUMEN
PURPOSE: To achieve the WHO cervical cancer elimination targets, countries globally must achieve 70% cervical cancer screening (CCS) coverage. We evaluated CCS uptake and predictors of screening positive at two public HIV care programs in western Kenya. METHODS: From October 2007 to February 2019, data from the Family AIDS Care and Education Services (FACES) and Academic Model Providing Access to Healthcare (AMPATH) programs in western Kenya were analyzed. The study population included women age 18-65 years enrolled in HIV care. Screening uptake was calculated annually and overall, determining the proportion of eligible women screened. Multivariate logistic regression assessed predictors of positive screening outcomes. RESULTS: There were 57,298 women living with HIV (WLWHIV) eligible for CCS across both programs during the study period. The mean age was 31.4 years (IQR, 25.9-37.8), and 39% were on antiretroviral therapy (ART) at the first CCS-eligible visit. Of all eligible women, 29.4% (95% CI, 29.1 to 29.8) underwent CCS during the study period, 27.0% (95% CI, 26.5 to 27.4) in the AMPATH program, and 35.6% (95% CI, 34.9 to 36.4) in the FACES program. Annual screening uptake varied greatly in both programs, with coverage as low as 1% of eligible WLWHIV during specific years. Age at first screening, CD4 count within 90 days of screening, current use of ART, and program (AMPATH v FACES) were each statistically significant predictors of positive screening. CONCLUSION: CCS uptake at two large HIV care programs in Kenya fell short of the WHO's 70% screening target. Screening rates varied significantly on the basis of the availability of funding specific to CCS, reflecting the limitations of vertical funding programs.
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Infecciones por VIH , Neoplasias del Cuello Uterino , Humanos , Femenino , Adulto , Adolescente , Adulto Joven , Persona de Mediana Edad , Anciano , Neoplasias del Cuello Uterino/prevención & control , Ácido Acético , Detección Precoz del Cáncer , Kenia/epidemiología , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Infecciones por VIH/terapiaRESUMEN
In people living with HIV, Kaposi Sarcoma (KS), a vascular neoplasm caused by KS herpesvirus (KSHV/HHV-8), remains one of the most common malignancies worldwide. Individuals living with HIV, receiving otherwise effective antiretroviral therapy, may present with extensive disease requiring chemotherapy. Hence, new therapeutic approaches are needed. The Wilms' tumor 1 (WT1) protein is overexpressed and associated with poor prognosis in several hematologic and solid malignancies and has shown promise as an immunotherapeutic target. We found that WT1 was overexpressed in >90% of a total 333 KS biopsies, as determined by immunohistochemistry and image analysis. Our largest cohort from ACTG, consisting of 294 cases was further analyzed demonstrating higher WT1 expression was associated with more advanced histopathologic subtypes. There was a positive correlation between the proportion of infected cells within KS tissues, assessed by expression of the KSHV-encoded latency-associated nuclear antigen (LANA), and WT1 positivity. Areas with high WT1 expression showed sparse T-cell infiltrates, consistent with an immune evasive tumor microenvironment. We show that major oncogenic isoforms of WT1 are overexpressed in primary KS tissue and observed WT1 upregulation upon de novo infection of endothelial cells with KSHV. KSHV latent viral FLICE-inhibitory protein (vFLIP) upregulated total and major isoforms of WT1, but upregulation was not seen after expression of mutant vFLIP that is unable to bind IKKÆ´ and induce NFκB. siRNA targeting of WT1 in latent KSHV infection resulted in decreased total cell number and pAKT, BCL2 and LANA protein expression. Finally, we show that ESK-1, a T cell receptor-like monoclonal antibody that recognizes WT1 peptides presented on MHC HLA-A0201, demonstrates increased binding to endothelial cells after KSHV infection or induction of vFLIP expression. We propose that oncogenic isoforms of WT1 are upregulated by KSHV to promote tumorigenesis and immunotherapy directed against WT1 may be an approach for KS treatment.
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Infecciones por VIH , Herpesvirus Humano 8 , Sarcoma de Kaposi , Humanos , Herpesvirus Humano 8/fisiología , Proteína Reguladora de Apoptosis Similar a CASP8 y FADD/metabolismo , Proteínas WT1/genética , Proteínas WT1/metabolismo , Células Endoteliales/metabolismo , Infecciones por VIH/metabolismo , Isoformas de Proteínas/metabolismo , Microambiente TumoralRESUMEN
Adolescent girls and young women (AGYW) have a disproportionately high incidence of HIV compared to males of the same age in Uganda. AGYW are a priority sub-group for daily oral Pre-Exposure Prophylaxis (PrEP), but their adherence has consistently remained low. Short Message Service (SMS) reminders could improve adherence to PrEP in AGYW. However, there is paucity of literature about acceptability of SMS reminders among AGYW using PrEP. We assessed the level of acceptability of SMS reminders as a PrEP adherence support tool and the associated factors, among AGYW in Mukono district, Central Uganda. We consecutively enrolled AGYW using PrEP in Mukono district in a cross sectional study. A structured pre-tested questionnaire was administered to participants by three trained research assistants. Data were analyzed in STATA 17.0; continuous variables were summarized using median and interquartile range (IQR) while categorical variables were summarized using frequencies and percentages. Acceptability of SMS was defined as willingness to accept SMS reminders to support PrEP adherence and was assessed using the seven constructs of the theoretical framework of acceptability. The relationship between the outcome and independent variables was assessed using a modified Poisson regression with robust standard errors. During the month of August 2022, 142 AGYW with median age 22 years (IQR; 18, 24) of whom 80.3% owned a personal mobile phone were assessed. SMS reminders were highly acceptable [90.9%, 95% Confidence Interval (CI) [84.9, 95.0]]. Rural residence was negatively associated with acceptability of SMS reminders (aPR: 0.92, 95% CI (0.84, 0.99)) and having belief that SMS cannot breach individual's privacy (aPR: 1.40, 95% CI (1.07, 1.84)) was positively associated with acceptability of SMS reminders. The acceptability of SMS reminders was high in this sub-population. SMS reminder can be leveraged to support AGYW to adhere to PrEP but should be designed in a way that maintains confidentiality, and supports AGYW living in rural settings.
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Introduction: Routine patient care data are increasingly used for biomedical research, but such "secondary use" data have known limitations, including their quality. When leveraging routine care data for observational research, developing audit protocols that can maximize informational return and minimize costs is paramount. Methods: For more than a decade, the Latin America and East Africa regions of the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium have been auditing the observational data drawn from participating human immunodeficiency virus clinics. Since our earliest audits, where external auditors used paper forms to record audit findings from paper medical records, we have streamlined our protocols to obtain more efficient and informative audits that keep up with advancing technology while reducing travel obligations and associated costs. Results: We present five key lessons learned from conducting data audits of secondary-use data from resource-limited settings for more than 10 years and share eight recommendations for other consortia looking to implement data quality initiatives. Conclusion: After completing multiple audit cycles in both the Latin America and East Africa regions of the IeDEA consortium, we have established a rich reference for data quality in our cohorts, as well as large, audited analytical datasets that can be used to answer important clinical questions with confidence. By sharing our audit processes and how they have been adapted over time, we hope that others can develop protocols informed by our lessons learned from more than a decade of experience in these large, diverse cohorts.
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BACKGROUND: After completion of TB treatment patients may remain at risk of co-morbidity and mortality. We determined the survival and predictors of all-cause mortality after completing TB treatment among ART-experienced patients. METHODS: This was a retrospective cohort analysis of all ART experienced patients who completed TB treatment at a specialist HIV clinic in Uganda, between 2009 and 2014. The patients were followed for five years after TB treatment. We determined the cumulative probability of death, and predictors of mortality using Kaplan-Meier methods and Cox proportional hazard models, respectively. RESULTS: A total 1,287 patients completed TB treatment between 2009 and 2014, of which 1,111 were included in the analysis. At TB treatment completion, the median age was 36 years (IQR: 31-42), 563 (50.7%) were males, and median CD4 cell count was 235 cells/mL (IQR: 139-366). The person-time at risk was 4410.60 person-years. The all-cause mortality rate was 15.42 (95% CI: 12.14-19.59) per 1000 person-years. The probability of death at five years was 6.9% (95%CI: 5.5- 8.8). In the multivariable analysis, CD4 count < 200 cells/mL was a predictor of all-cause mortality (aHR = 1.81, 95%CI:1.06-3.11, p = 0.03) alongside history of retreatment (aHR = 2.12, 95%CI: 1.16-3.85, p = 0.01). CONCLUSION: Survival post TB treatment in ART experienced PLHIV is reasonably good. Most deaths occur within two years after TB treatment completion. Patients with a low CD4 count and those with a history of retreatment have an increased risk of mortality which underscores the need for TB prophylaxis, detailed assessment, and close monitoring after completion of TB treatment.
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Infecciones por VIH , Tuberculosis , Masculino , Humanos , Adulto , Femenino , Tuberculosis/tratamiento farmacológico , Estudios Retrospectivos , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Estudios de Cohortes , Modelos de Riesgos ProporcionalesRESUMEN
Kaposi's sarcoma (KS) is an endothelial cancer caused by the Kaposi's sarcoma-associated herpesvirus (KSHV) and is one of the most common cancers in sub-Saharan Africa. In limited-resource settings, traditional pathology infrastructure is often insufficient for timely diagnosis, leading to frequent diagnoses at advanced-stage disease where survival is poor. In this study, we investigate molecular diagnosis of KS performed in a point-of-care device to circumvent the limited infrastructure for traditional diagnosis. Using 506 mucocutaneous biopsies collected from patients at three HIV clinics in Uganda, we achieved 97% sensitivity, 92% specificity, and 96% accuracy compared to gold standard U.S.-based pathology. The results presented in this manuscript show that LAMP-based quantification of KSHV DNA extracted from KS-suspected biopsies has the potential to serve as a successful diagnostic for the disease and that diagnosis may be accurately achieved using a point-of-care device, reducing the barriers to obtaining KS diagnosis while increasing diagnostic accuracy.
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BACKGROUND: High prevalence of HIV and hypertension in sub-Saharan Africa puts adults living with HIV (ALWH) at high risk of end-organ complications. Both World Health Organization (WHO) and national guidelines recommend screening and treatment of hypertension among ALWH on antiretroviral therapy (ART). We evaluated the implementation of hypertension screening among adults on ART at three Uganda Cares Primary care facilities. METHODS: Using a sequential explanatory mixed-methods approach, we reviewed patient records, and interviewed both patients and providers during 2018 and 2019. We obtained demographics, clinical and blood pressure (BP) measurements via records review. We estimate the period prevalence of screening and use adjusted modified Poisson regression models to evaluate predictors of screening. In-depth interviews were analysed using a thematic approach to explain the observed prevalence and predictors of BP screening. RESULTS: Records for 1426 ALWH were reviewed. Patients had a median age of 35 years and 65% of them were female. Most were on ART (89% on first-line) with a median duration of 4 years. Only 262 (18%) were overweight or obese with a body mass index (BMI) > 25 Kg/M2. In 2017 or 2018 patients made a median of 3 visits and 783 patients had a BP recorded, hence a period prevalence 55%. Older age, male sex, more clinic visits, and clinic site were associated with screening in the adjusted analyses. Erratic BP screening was corroborated by patients' and providers' interviews. Challenges included; high patient numbers, low staffing, provider apathy, no access to treatment, and lack of functioning of BP equipment. CONCLUSION: Almost half of regular HIV clinic attendees at these prototypical primary care HIV clinics were not screened for hypertension for a whole year. Improving BP screening requires attention to address modifiable challenges and ensure local buy-in beyond just providing equipment.
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Infecciones por VIH , Hipertensión , Adulto , Instituciones de Atención Ambulatoria , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Humanos , Hipertensión/diagnóstico , Hipertensión/tratamiento farmacológico , Hipertensión/epidemiología , Masculino , Prevalencia , Atención Primaria de Salud , Uganda/epidemiologíaRESUMEN
BACKGROUND: The most effective treatment for advanced AIDS-associated Kaposi sarcoma is paclitaxel or pegylated liposomal doxorubicin (PLD); neither is routinely used in sub-Saharan Africa due to limited availability and high cost. We examined the clinical impact, costs, and cost-effectiveness of paclitaxel or PLD in Kenya, compared with etoposide or bleomycin-vincristine. METHODS: In this study, we use the Cost-Effectiveness of Preventing AIDS Complications (CEPAC)-International Model to project clinical outcomes and costs among people living with HIV and advanced Kaposi sarcoma on antiretroviral therapy. We compared four different treatment strategies: etoposide, bleomycin-vincristine, paclitaxel, or PLD. We derived cohort characteristics and costs from the Kenyan Academic Model for Providing Access to Healthcare network, and adverse events, efficacy, and mortality from clinical trials. We projected model outcomes over a lifetime and included life expectancy, per-person lifetime costs, and incremental cost-effectiveness ratios (ICERs). We conducted budget impact analysis for 5-year total costs and did deterministic and probabilistic sensitivity analyses to evaluate the effect of uncertainty in input parameters. FINDINGS: We found that paclitaxel would be more effective than bleomycin-vincristine and would increase life expectancy by 4·2 years per person. PLD would further increase life expectancy by 0·6 years per person. Paclitaxel would be the most cost-effective strategy (ICER US$380 per year-of-life-saved compared with bleomycin-vincristine) and would remain cost-effective across a range of scenarios. PLD would be cost-effective compared with paclitaxel if its price were reduced to $100 per cycle (base case $180 per cycle). Implementing paclitaxel instead of bleomycin-vincristine would save approximately 6400 life-years and would increase the overall 5-year Kenyan health-care costs by $3·7 million; increased costs would be primarily related to ongoing HIV care given improved survival. INTERPRETATION: Paclitaxel would substantially increase life expectancy and be cost-effective compared with bleomycin-vincristine for advanced AIDS-associated Kaposi sarcoma in Kenya and should be the standard of care. PLD would further improve survival and be cost-effective with a 44% price reduction. FUNDING: US National Institutes of Health and Massachusetts General Hospital. TRANSLATION: For the Swahili translation of the abstract see Supplementary Materials section.
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Síndrome de Inmunodeficiencia Adquirida , Infecciones por VIH , Sarcoma de Kaposi , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Bleomicina/uso terapéutico , Análisis Costo-Beneficio , Etopósido/uso terapéutico , Infecciones por VIH/complicaciones , Humanos , Kenia , Paclitaxel/efectos adversos , Paclitaxel/uso terapéutico , Sarcoma de Kaposi/inducido químicamente , Sarcoma de Kaposi/complicaciones , Sarcoma de Kaposi/tratamiento farmacológico , Vincristina/uso terapéuticoRESUMEN
BACKGROUND: Psychotic disorders contribute to significant morbidity and mortality partly due to the chronicity of the illness and high relapse rates. Delivering psycho-education messages about disease etiology, their signs and symptoms and the benefits of treatment adherence have been shown to improve clinical outcomes among individuals with psychoses. However, little has been done to examine the feasibility and efficacy of this intervention in low resourced settings. OBJECTIVE: Our primary objective will be to determine the feasibility of recruiting and retaining patients with a first episode psychosis (FEP) and for the secondary objective, we will determine the preliminary efficacy of psycho-education on illness self-management, stigma, adherence to medications and symptom severity. HYPOTHESIS: We hypothesize that (i) we will recruit 70% of eligible participants and accrue a sample size of 80 over 20-weeks, retaining 80% of the sample size for 24 weeks, (ii) the intervention will lead to improvement in clinical outcomes (described above). METHODS: We will recruit 80 adult patients who have been diagnosed with a FEP, received antipsychotic medication at Butabika Hospital and reside within 21km from the Hospital. Trained village health team (VHTs) members will deliver 6 psycho-education sessions to 40 participants and their family members (intervention arm). Participants in the control arm (n = 40) will receive routine care. We will document how feasible it will be to recruit and retain participants over 24 weeks and document the preliminary efficacy of the intervention on illness self-management, stigma, adherence to medications and severity of symptoms. DATA ANALYSIS: We will document the proportion of participants who consent and get recruited, the proportion of those who will get retained and reasons for drop out. We will conduct an intention to treat analysis comparing the groups at weeks 4, 12, 24 and assess the effect of the intervention on the clinical outcomes (described above). We will use the Bonferroni approach to correct for multiple comparisons. TRIAL REGISTRATION: Clinical trials.gov registration number: NCT04602585.
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Antipsicóticos , Trastornos Psicóticos , Adulto , Antipsicóticos/uso terapéutico , Estudios de Factibilidad , Humanos , Proyectos Piloto , Trastornos Psicóticos/diagnóstico , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , UgandaRESUMEN
BACKGROUND: Kaposi sarcoma is one of the most prevalent HIV-associated malignancies in sub-Saharan Africa and is often diagnosed at advanced stage of disease. Only 50% of KS patients who qualify for chemotherapy receive it and adherence is sub-optimal. METHODS: 57 patients > 18 years with newly diagnosed KS within the AMPATH clinic network in Western Kenya were purposively selected to participate in semi-structured interviews stratified by whether they had completed, partially completed, or not completed chemotherapy for advanced stage KS. We based the interview guide and coding framework on the situated Information, Motivation, Behavioral Skills (sIMB) framework, in which the core patient centered IMB constructs are situated into the socioecological context of receiving care. RESULTS: Of the 57 participants, the median age was 37 (IQR 32-41) and the majority were male (68%). Notable barriers to chemotherapy initiation and adherence included lack of financial means, difficulty with convenience of appointments such as distance to facility, appointment times, long lines, limited appointments, intrapersonal barriers such as fear or hopelessness, and lack of proper or sufficient information about chemotherapy. Factors that facilitated chemotherapy initiation and adherence included health literacy, motivation to treat symptoms, improvement on chemotherapy, prioritization of self-care, resilience while experiencing side effects, ability to carry out behavioral skills, obtaining national health insurance, and free chemotherapy. CONCLUSION: Our findings about the barriers and facilitators to chemotherapy initiation and adherence for KS in Western Kenya support further work that promotes public health campaigns with reliable cancer and chemotherapy information, improves education about the chemotherapy process and side effects, increases oncology service ability, supports enrollment in national health insurance, and increases incorporation of chronic disease care into existing HIV treatment networks.
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INTRODUCTION: The experience of stigma can be multifaceted for people with HIV and cancer. Kaposi's sarcoma (KS), one of the most common HIV-associated cancers in sub-Saharan Africa, often presents with visible skin lesions that may put people at risk for stigmatization. In this way, HIV-associated KS is unique, as people with KS can experience stigma associated with HIV, cancer, and skin disease simultaneously. The aim of this study is to characterize the intersectionality of HIV-related, cancer-related and skin disease-related stigma in people living with HIV and KS. METHODS: We used a convergent mixed-methods approach nested within a longitudinal study of people with HIV-associated KS in western Kenya. Between February 2019 and December 2020, we collected quantitative surveys among all participants and conducted semi-structured interviews among a purposive sample of participants. Quantitative surveys were adapted from the abridged Berger HIV Stigma Scale to assess overall stigma, HIV-related stigma, cancer-related stigma, and skin disease-related stigma. Qualitative data were coded using stigma constructs from the Health Stigma and Discrimination Framework. RESULTS: In 88 semi-structured interviews, stigma was a major barrier to KS diagnosis and treatment among people with HIV-associated KS. Participant's stories of stigma were dominated by HIV-related stigma, more than cancer-related or skin disease-related stigma. However, quantitative stigma scores among the 117 participants were similar for HIV-related (Median: 28.00; IQR: 28.0, 34.0), cancer-related (Median: 28.0; IQR: 28.0, 34.8), and skin disease-related stigma (Median: 28.0; IQR: 27.0, 34.0). In semi-structured interviews, cancer-related and skin disease-related stigma were more subtle contributors; cancer-related stigma was linked to fatalism and skin-related stigma was linked to visible disease. Participants reported resolution of skin lesions contributed to lessening stigma over time; there was a significant decline in quantitative scores of overall stigma in time since KS diagnosis (adjusted ß = -0.15, p <0.001). CONCLUSIONS: This study highlights the role mixed-method approaches can play in better understanding stigma in people living with both HIV and cancer. While HIV-related stigma may dominate perceptions of stigma among people with KS in Kenya, intersectional experiences of stigma may be subtle, and quantitative evaluation alone may be insufficient to understand intersectional stigma in certain contexts.
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Infecciones por VIH , Sarcoma de Kaposi , Infecciones por VIH/complicaciones , Humanos , Kenia , Estudios Longitudinales , Sarcoma de Kaposi/complicacionesRESUMEN
BACKGROUND: Although HIV-associated Kaposi sarcoma (KS) is frequently diagnosed at an advanced stage in sub-Saharan Africa, reasons for diagnostic delays have not been well described. METHODS: We enrolled patients >18 years with newly diagnosed KS between 2016 and 2019 into the parent study, based in western Kenya. We then purposively selected 30 participants with diversity of disease severity and geographic locations to participate in semistructured interviews. We used 2 behavioral models in developing the codebook for this analysis: situated Information, Motivation, and Behavior framework and Andersen model of total patient delay. We then analyzed the interviews using framework analysis. RESULTS: The most common patient factors that delayed diagnosis were lack of KS awareness, seeking traditional treatments, lack of personal efficacy, lack of social support, and fear of cancer, skin biopsy, amputation, and HIV diagnosis. Health system factors that delayed diagnosis included previous negative health care interactions, incorrect diagnoses, lack of physical examination, delayed referral, and lack of tissue biopsy availability. Financial constraints were prominent barriers for patients to access and receive care. Facilitators for diagnosis included being part of an HIV care network, living near health facilities, trust in the health care system, desire to treat painful or disfiguring lesions, and social support. CONCLUSIONS: Lack of KS awareness among patients and providers, stigma surrounding diagnoses, and health system referral delays were barriers in reaching KS diagnosis. Improved public health campaigns, increased availability of biopsy and pathology facilities, and health provider training about KS are needed to improve early diagnosis of KS.
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Infecciones por VIH , Sarcoma de Kaposi , Diagnóstico Tardío , Infecciones por VIH/diagnóstico , Humanos , Kenia , Investigación Cualitativa , Sarcoma de Kaposi/diagnósticoRESUMEN
BACKGROUND: For people with advanced-stage Kaposi's sarcoma (KS), a common HIV-associated malignancy in sub-Saharan Africa, mortality is estimated to be 45% within 2 years after KS diagnosis, despite increasingly wide-spread availability of antiretroviral therapy and chemotherapy. For advanced-stage KS, chemotherapy in addition to antiretroviral therapy improves outcomes and saves lives, but currently, only ~50% of people with KS in western Kenya who have an indication for chemotherapy actually receive it. This protocol describes the evaluation of a multicomponent patient navigation strategy that addresses common barriers to service penetration of and fidelity to evidence-based chemotherapy among people with advanced-stage KS in Kenya. METHODS: This is a hybrid type III effectiveness-implementation study using a non-randomized, pre- post-design nested within a longitudinal cohort. We will compare the delivery of evidence-based chemotherapy for advanced-stage KS during the period before (2016-2020) to the period after (2021-2024), the rollout of a multicomponent patient navigation strategy. The multicomponent patient navigation strategy was developed in a systematic process to address key determinants of service penetration of and fidelity to chemotherapy in western Kenya and includes (1) physical navigation and care coordination, (2) video-based education, (3) travel stipend, (4) health insurance enrollment assistance, (5) health insurance stipend, and (6) peer mentorship. We will compare the pre-navigation period to the post-navigation period to assess the impact of this multicomponent patient navigation strategy on (1) implementation outcomes: service penetration (chemotherapy initiation) and fidelity (chemotherapy completion) and (2) service and client outcomes: timeliness of cancer care, mortality, quality of life, stigma, and social support. We will also describe the implementation process and the determinants of implementation success for the multicomponent patient navigation strategy. DISCUSSION: This study addresses an urgent need for effective implementation strategies to improve the initiation and completion of evidence-based chemotherapy in advanced-stage KS. By using a clearly specified, theory-based implementation strategy and validated frameworks, this study will contribute to a more comprehensive understanding of how to improve cancer treatment in advanced-stage KS.
RESUMEN
BACKGROUND: Asymptomatic Cryptococcal Antigenemia (CrAg) patients develop meningitis within a month of testing positive. Pre-emptive antifungal therapy can prevent progression to Cryptococcal meningitis (CM). In April 2016, a national CrAg screening program was initiated in 206 high-volume health facilities that provide antiretroviral therapy in Uganda. We report the evaluation of the CrAg screening cascade focusing on linkage to care, fluconazole therapy for 10 weeks and 6 months follow up, and ART initiation in a subset of facilities. METHODS: We conducted a retrospective, cross-sectional survey of patients with CD4 < 100 at seven urban and seven rural facilities after 1 year of program implementation. We quantified the number of patients who transitioned through the steps of the CrAg screening cascade over six-months follow-up. We defined cascade completion as a pre-emptive fluconazole prescription for the first 10 weeks. We conducted semi-structured interviews with lab personnel and clinic staff to assess functionality of the CrAg screening program. Data was collected using REDCap. RESULTS: We evaluated 359 patient records between April 2016 to March 2017; the majority (358/359, 99.7%) were from government owned health facilities and just over half (193/359, 53.8%) had a median baseline CD4 cell count of < 50 cell/µL. Overall, CrAg screening had been performed in 255/359 (71.0, 95% CI, 66.0-75.7) of patients' records reviewed, with a higher proportion among urban facilities (170/209 (81.3, 95% CI, 75.4-86.4)) than rural facilities (85/150 (56.7, 95% CI, 48.3-64.7)). Among those who were CrAg screened, 56/255 (22.0, 95% CI, 17.0-27.5%) had cryptococcal antigenemia, of whom 47/56 (83.9, 95% CI, 71.7-92.4%) were initiated on pre-emptive therapy with fluconazole and 8/47 (17.0, 95% CI, 7.6-30.8%) of these were still receiving antifungal therapy at 6 months follow up. At least one CNS symptom was present in 70% (39/56) of those with antigenemia. In patients who had started ART, almost 40% initiated ART prior to CrAg screening. Inadequacy of equipment/supplies was reported by 15/26 (58%) of personnel as a program barrier, while 13/26 (50%) reported a need for training about CM and CrAg screening. CONCLUSION: There was a critical gap in the follow-up of patients after initiation on fluconazole therapy. ART had been initiated in almost 40% of patients prior to CrAg screening.. Higher antigenemia patients presenting with CNS symptoms could be related to late presentation. There is need to address these gaps after a more thorough evaluation.