Uptake, adherence and discontinuation of antiretroviral treatment in the Kibera slum, Nairobi, Kenya

Background: As antiretroviral treatment (ART) is being scaled-up, long-term success depends on high adherence to ART and retention in care. Rapid urbanization and growing slum populations present specific challenges for sustaining HIV-infected patients on ART. Aim: To study determinants for low adherence to ART in an urban slum in sub-Saharan Africa and to explore factors related to drop-out from ART. Methods: All studies were conducted at the Médecins Sans Frontières s (MSF) or at the African Medical Research Foundation s (AMREF) HIV clinics in the Kibera slum, Nairobi, Kenya. Study I: 26 patients eligible for ART at the MSF clinic who choose to not initiate ART were interviewed to understand underlying reasons. Study II: Patient records were reviewed to study access to ART during the violence in Kibera following the general elections in Kenya 2007/08. Study III: Adherence to ART and drop-out from the programme was analyzed retrospectively through review of 830 patient records. Study IV: 20 patients known to have dropped-out of ART to seek alternative care/cure, were interviewed about their reasons. Study V: A prospective cohort study of 800 patients to analyze dose-adherence to ART by creating an adherence index based on dosing, timing and special instructions and performing Cox-regression survival analysis to study time to drop-out. Findings: Study I: The main reason for not accepting ART was fear of taking medication on an empty stomach due to lack of food. Study II: During post-election turbulence in January 2008, 42% of 447 scheduled appointments were missed compared to 14% in January 2007. Study III: 27% of ART patients had a mean adherence below 95%. No factor remained independently associated with low adherence. 29% dropped out more than 90 days after the last prescribed dose. Residence in Kibera was associated with drop-out. The probability of remaining on treatment was 0.83 at 6 months, 0.74 at 12 months and 0.65 at 24 months. Study IV: The most important reasons for dropping-out from ART related to religious beliefs and traditional medicine were: patients firm belief that traditional medicine was more effective/had fewer side effects compared to biomedical medicine; faith, praying and religious practices to seek cure from HIV; negative attitudes from religious leaders; and; important personal trigger events. Study V: Among 800 patients, 11% were non-adherent at 6 months follow-up (dose-adherence<95%). Undisclosed HIV-status and living below the poverty limit were significant predictors of adherence <95%. Using the adherence index, also taking adherence to timing and special food instructions into account, 38% of patients were defined as non-adherent. Lack of treatment buddy and low education were significant risk factors. Almost 1 in 4 dropped-out from the ART programme for more than 90 days after the last prescribed dose. Cox regression analyses showed a significantly higher hazard ratio for people who lacked a treatment buddy for support. Conclusion: Sustaining HIV patients on ART in high-risk and highly mobile settings such as urban slums is a major future challenge. The high proportion of patients dropping out from ART and being non-adherent must be addressed using context-specific solutions. It is important to invest more in poverty reduction strategies in general, but also to encourage an open, non-judgmental discussion between patients and providers around possible foreseen challenges to treatment maintenance e.g. food shortages, religion and traditional medicine, in order to strengthen uptake and adherence to ART and to reduce drop-out from ART, especially important in resource-poor settings where stigma, and poverty is prevalent

Long-Term Adherence to Antiretroviral Treatment and Program Drop-Out in a High-Risk Urban Setting in Sub-Saharan Africa: A Prospective Cohort Study

Seventy percent of urban populations in sub-Saharan Africa live in slums. Sustaining HIV patients in these high-risk and highly mobile settings is a major future challenge. This study seeks to assess program retention and to find determinants for low adherence to antiretroviral treatment (ART) and drop-out from an established HIV/ART program in Kibera, Nairobi, one of Africa's largest informal urban settlements.A prospective open cohort study of 800 patients was performed at the African Medical Research Foundation (AMREF) clinic in the Kibera slum. Adherence to ART and drop-out from the ART program were independent outcomes. Two different adherence measures were used: (1) “dose adherence” (the proportion of a prescribed dose taken over the past 4 days) and (2) “adherence index” (based on three adherence questions covering dosing, timing and special instructions). Drop-out from the program was calculated based on clinic appointment dates and number of prescribed doses, and a patient was defined as being lost to follow-up if over 90 days had expired since the last prescribed dose. More than one third of patients were non-adherent when all three aspects of adherence – dosing, timing and special instructions – were taken into account. Multivariate logistic regression revealed that not disclosing HIV status, having a low level of education, living below the poverty limit (US$ 2/day) and not having a treatment buddy were significant predictors for non-adherence. Additionally, one quarter of patients dropped out for more than 90 days after the last prescribed ART dose. Not having a treatment buddy was associated with increased risk for drop-out (hazard ratio 1.4, 95% CI = 1.0–1.9).These findings point to the dilemma of trying to sustain a growing number of people on life-long ART in conditions where prevailing stigma, poverty and food shortages threatens the long-term success of HIV treatment

Robust T cell immunity in convalescent individuals with asymptomatic or mild COVID-19

SARS-CoV-2-specific memory T cells will likely prove critical for long-term immune protection against COVID-19. Here, we systematically mapped the functional and phenotypic landscape of SARS-CoV-2-specific T cell responses in unexposed individuals, exposed family members, and individuals with acute or convalescent COVID-19. Acute-phase SARS-CoV-2-specific T cells displayed a highly activated cytotoxic phenotype that correlated with various clinical markers of disease severity, whereas convalescent-phase SARS-CoV-2-specific T cells were polyfunctional and displayed a stem-like memory phenotype. Importantly, SARS-CoV-2-specific T cells were detectable in antibody-seronegative exposed family members and convalescent individuals with a history of asymptomatic and mild COVID-19. Our collective dataset shows that SARS-CoV-2 elicits broadly directed and functionally replete memory T cell responses, suggesting that natural exposure or infection may prevent recurrent episodes of severe COVID-19

Varför avbryter HIV-patienter sin behandling?

Följsamhet till bromsmediciner mot HIV är viktig då allt fler patienter i världen ges behandling och dålig följsamhet till mediciner har visat ge resistensutveckling. Syftet med denna studie var att få förståelse för varför patienter på Huddinges HIV-mottagning avbryter sin behandling. Kvalitativa halvstrukturerade intervjuer gjordes med sju patienter som på eget eller läkarens initiativ avbrutit behandling. En induktiv tematisk analys av data visade att patienternas uppfattning om de viktigaste orsakerna till avbrottet från behandling var fysiska biverkningar, tabletternas negativa inverkan på vardagen och läkarens inflytande. Resultaten får stöd i tidigare forskning kring följsamhet till bromsmediciner. Vidare studier på området kan hjälpa patienter att få bättre behandling mot HIV/AIDS

Peripheral Oxygen Saturation Facilitates Assessment of Respiratory Dysfunction in the Sequential Organ Failure Assessment Score with Implications for the Sepsis-3 Criteria

OBJECTIVES: Sequential Organ Failure Assessment score is the basis of the Sepsis-3 criteria and requires arterial blood gas analysis to assess respiratory function. Peripheral oxygen saturation is a noninvasive alternative but is not included in neither Sequential Organ Failure Assessment score nor Sepsis-3. We aimed to assess the association between worst peripheral oxygen saturation during onset of suspected infection and mortality. DESIGN: Cohort study of hospital admissions from a main cohort and emergency department visits from four external validation cohorts between year 2011 and 2018. Data were collected from electronic health records and prospectively by study investigators. SETTING: Eight academic and community hospitals in Sweden and Canada. PATIENTS: Adult patients with suspected infection episodes. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The main cohort included 19,396 episodes (median age, 67.0 [53.0-77.0]; 9,007 [46.4%] women; 1,044 [5.4%] died). The validation cohorts included 10,586 episodes (range of median age, 61.0-76.0; women 42.1-50.2%; mortality 2.3-13.3%). Peripheral oxygen saturation levels 96-95% were not significantly associated with increased mortality in the main or pooled validation cohorts. At peripheral oxygen saturation 94%, the adjusted odds ratio of death was 1.56 (95% CI, 1.10-2.23) in the main cohort and 1.36 (95% CI, 1.00-1.85) in the pooled validation cohorts and increased gradually below this level. Respiratory assessment using peripheral oxygen saturation 94-91% and less than 91% to generate 1 and 2 Sequential Organ Failure Assessment points, respectively, improved the discrimination of the Sequential Organ Failure Assessment score from area under the receiver operating characteristics 0.75 (95% CI, 0.74-0.77) to 0.78 (95% CI, 0.77-0.80; p < 0.001). Peripheral oxygen saturation/Fio2ratio had slightly better predictive performance compared with peripheral oxygen saturation alone, but the clinical impact was minor. CONCLUSIONS: These findings provide evidence for assessing respiratory function with peripheral oxygen saturation in the Sequential Organ Failure Assessment score and the Sepsis-3 criteria. Our data support using peripheral oxygen saturation thresholds 94% and 90% to get 1 and 2 Sequential Organ Failure Assessment respiratory points, respectively. This has important implications primarily for emergency practice, rapid response teams, surveillance, research, and resource-limited settings

Discriminatory plasma biomarkers predict specific clinical phenotypes of necrotizing soft-tissue infections

BACKGROUND: Necrotizing soft-tissue infections (NSTIs) are rapidly progressing infections frequently complicated by septic shock and associated with high mortality. Early diagnosis is critical for patient outcome, but challenging due to vague initial symptoms. Here, we identified predictive biomarkers for NSTI clinical phenotypes and outcomes using a prospective multicenter NSTI patient cohort. METHODS: Luminex multiplex assays were used to assess 36 soluble factors in plasma from NSTI patients with positive microbiological cultures (n = 251 and n = 60 in the discovery and validation cohorts, respectively). Control groups for comparative analyses included surgical controls (n = 20), non-NSTI controls (i.e., suspected NSTI with no necrosis detected upon exploratory surgery, n = 20), and sepsis patients (n = 24). RESULTS: Thrombomodulin was identified as a unique biomarker for detection of NSTI (AUC, 0.95). A distinct profile discriminating mono- (type II) versus polymicrobial (type I) NSTI types was identified based on differential expression of IL-2, IL-10, IL-22, CXCL10, Fas-ligand, and MMP9 (AUC >0.7). While each NSTI type displayed a distinct array of biomarkers predicting septic shock, granulocyte CSF (G-CSF), S100A8, and IL-6 were shared by both types (AUC >0.78). Finally, differential connectivity analysis revealed distinctive networks associated with specific clinical phenotypes. CONCLUSIONS: This study identifies predictive biomarkers for NSTI clinical phenotypes of potential value for diagnostic, prognostic, and therapeutic approaches in NSTIs. TRIAL REGISTRATION: ClinicalTrials.gov NCT01790698. FUNDING: Center for Innovative Medicine (CIMED); Region Stockholm; Swedish Research Council; European Union; Vinnova; Innovation Fund Denmark; Research Council of Norway; Netherlands Organisation for Health Research and Development; DLR Federal Ministry of Education and Research; and Swedish Children’s Cancer Foundation

Inhaled ciclesonide in adults hospitalised with COVID-19: a randomised controlled open-label trial (HALT COVID-19)

Objective To assess the efficacy of inhaled ciclesonide in reducing the duration of oxygen therapy (an indicator of time to clinical improvement) among adults hospitalised with COVID-19.Design Multicentre, randomised, controlled, open-label trial.Setting 9 hospitals (3 academic hospitals and 6 non-academic hospitals) in Sweden between 1 June 2020 and 17 May 2021.Participants Adults hospitalised with COVID-19 and receiving oxygen therapy.Intervention Inhaled ciclesonide 320 µg two times a day for 14 days versus standard care.Main outcome measures Primary outcome was duration of oxygen therapy, an indicator of time to clinical improvement. Key secondary outcome was a composite of invasive mechanical ventilation/death.Results Data from 98 participants were analysed (48 receiving ciclesonide and 50 receiving standard care; median (IQR) age, 59.5 (49–67) years; 67 (68%) men). Median (IQR) duration of oxygen therapy was 5.5 (3–9) days in the ciclesonide group and 4 (2–7) days in the standard care group (HR for termination of oxygen therapy 0.73 (95% CI 0.47 to 1.11), with the upper 95% CI being compatible with a 10% relative reduction in oxygen therapy duration, corresponding to a &lt;1 day absolute reduction in a post-hoc calculation). Three participants in each group died/received invasive mechanical ventilation (HR 0.90 (95% CI 0.15 to 5.32)). The trial was discontinued early due to slow enrolment.Conclusions In patients hospitalised with COVID-19 receiving oxygen therapy, this trial ruled out, with 0.95 confidence, a treatment effect of ciclesonide corresponding to more than a 1 day reduction in duration of oxygen therapy. Ciclesonide is unlikely to improve this outcome meaningfully.Trial registration number NCT04381364

The impact of hemodialysis on mortality risk and cause of death in Staphylococcus aureus endocarditis

Abstract Background The risk of infective endocarditis (IE) is markedly increased in patients receiving chronic hemodialysis compared with the general population, but outcome data are sparse. The present study investigated causes and risk factors of mortality in a hemodialysis-treated end-stage kidney disease- (ESKD) and a non-ESKD population with staphylococcus (S.) aureus endocarditis. Methods Hemodialysis-treated ESKD patients with S. aureus endocarditis were identified from Danish National Registries and Non-ESKD patients from The East Danish Database on Endocarditis. For establishing the cause of death The Danish Registry of Cause of Death was used. Independent risk factors of outcome were identified in multivariable Cox regression models. Results One hundred twenty-one hemodialysis patients and 190 non-ESKD patients with S. aureus endocarditis were included during 1996–2012 and 2002–2012, respectively. The all-cause in-hospital mortality was 22.3% in hemodialysis- and 24.7% in non-ESKD patients. One-year mortality, excluding in-hospital mortality, was 26.4% in hemodialysis patients and 15.2% in non-ESKD patients. The hazard ratio of all-cause mortality in hemodialysis was 2.64 (95% CI 1.70–4.10) at &gt; 70 days after admission compared with non-ESKD. Age (HR 1.03 (95% CI 1.02–1.04)) and diabetes mellitus (HR 2.17 (95% CI 1.54–3.10)) were independent risk factors of all-cause mortality. The hazard ratio of cardiovascular death in hemodialysis was 3.20 (95% CI 1.78–5.77) at &gt; 81 days after admission compared with non-ESKD. Age and diabetes mellitus were independently related to cardiovascular death. Conclusion All-cause in-hospital mortality rates were similar in hemodialysis and non-ESKD patients with S. aureus endocarditis whereas one-year mortality rates were significantly increased in the hemodialysis population