ABSTRACT
BACKGROUND: The autoimmune lymphoproliferative syndrome (ALPS) is a noninfectious and nonmalignant lymphoproliferative disease frequently associated with autoimmune cytopenia resulting from defective FAS signaling. We previously described germline monoallelic FAS (TNFRSF6) haploinsufficient mutations associated with somatic events, such as loss of heterozygosity on the second allele of FAS, as a cause of ALPS-FAS. These somatic events were identified by sequencing FAS in DNA from double-negative (DN) T cells, the pathognomonic T-cell subset in ALPS, in which the somatic events accumulated. OBJECTIVE: We sought to identify whether a somatic event affecting the FAS-associated death domain (FADD) gene could be related to the disease onset in 4 unrelated patients with ALPS carrying a germline monoallelic mutation of the FADD protein inherited from a healthy parent. METHODS: We sequenced FADD and performed array-based comparative genomic hybridization using DNA from sorted CD4+ or DN T cells. RESULTS: We found homozygous FADD mutations in the DN T cells from all 4 patients, which resulted from uniparental disomy. FADD deficiency caused by germline heterozygous FADD mutations associated with a somatic loss of heterozygosity was a phenocopy of ALPS-FAS without the more complex symptoms reported in patients with germline biallelic FADD mutations. CONCLUSIONS: The association of germline and somatic events affecting the FADD gene is a new genetic cause of ALPS.
Subject(s)
Autoimmune Lymphoproliferative Syndrome , Fas-Associated Death Domain Protein , Humans , Apoptosis/genetics , Autoimmune Diseases/genetics , Autoimmune Lymphoproliferative Syndrome/genetics , Comparative Genomic Hybridization , DNA , fas Receptor/genetics , Fas-Associated Death Domain Protein/genetics , Fas-Associated Death Domain Protein/metabolism , Germ Cells/pathology , MutationABSTRACT
Uveal melanoma is the most common primary intraocular malignancy in adults. Up to 50% of UM patients develop metastatic disease, usually in the liver. When metastatic, the prognosis is poor, and few treatment options exist. Here, we investigated the feasibility of establishing patient-derived xenografts (PDXs) from a patient's tumor in order to screen for therapies that the patient could benefit from. Samples obtained from 29 primary tumors and liver metastases of uveal melanoma were grafted into SCID mice. PDX models were successfully established for 35% of primary patient tumors and 67% of liver metastases. The tumor take rate was proportional to the risk of metastases. PDXs showed the same morphology, the same GNAQ/11, BAP1, and SF3B1 mutations, and the same chromosome 3 and 8q status as the corresponding patient samples. Six PDX models were challenged with two compounds for 4 weeks. We show that, for 31% of patients with high or intermediate risk of metastasis, the timing to obtain efficacy results on PDX models derived from their primary tumors was compatible with the selection of the therapy to treat the patient after relapse. PDXs could thus be a valid tool ("avatar") to select the best personalized therapy for one third of patients that are most at risk of relapse.
Subject(s)
Liver Neoplasms , Neoplasm Recurrence, Local , Adult , Animals , Mice , Humans , Feasibility Studies , Heterografts , Mice, SCID , Liver Neoplasms/genetics , RecurrenceABSTRACT
Uveal melanoma (UM) is a rare cancer resulting from the transformation of melanocytes in the uveal tract. Integrative analysis has identified four molecular and clinical subsets of UM. To improve our molecular understanding of UM, we performed extensive multi-omics characterization comparing two aggressive UM patient-derived xenograft models with normal choroidal melanocytes, including DNA optical mapping, specific histone modifications, and DNA topology analysis using Hi-C. Our gene expression and cytogenetic analyses suggest that genomic instability is a hallmark of UM. We also identified a recurrent deletion in the BAP1 promoter resulting in loss of expression and associated with high risk of metastases in UM patients. Hi-C revealed chromatin topology changes associated with the upregulation of PRAME, an independent prognostic biomarker in UM, and a potential therapeutic target. Our findings illustrate how multi-omics approaches can improve our understanding of tumorigenesis and reveal two distinct mechanisms of gene expression dysregulation in UM.
Subject(s)
Melanoma , Multiomics , Humans , Melanoma/pathology , Melanocytes/metabolism , DNA , Antigens, Neoplasm/geneticsABSTRACT
Keloid scars are hypertrophic and proliferating pathological scars extending beyond the initial lesion and without tendency to regression. Usually, keloids are considered and treated as a single entity but clinical observations suggest heterogeneity in keloid morphologies with distinction of superficial/extensive and nodular entities. Within a keloid, heterogeneity could also be detected between superficial and deep dermis or centre and periphery. Focusing on fibroblasts as main actors of keloid formation, we aimed at evaluating intra- and inter-keloid fibroblast heterogeneity by analysing their gene expression and functional capacities (proliferation, migration, traction forces), in order to improve our understanding of keloid pathogenesis. Fibroblasts were obtained from centre, periphery, papillary and reticular dermis from extensive or nodular keloids and were compared to control fibroblasts from healthy skin. Transcriptional profiling of fibroblasts identified a total of 834 differentially expressed genes between nodular and extensive keloids. Quantification of ECM-associated gene expression by RT-qPCR brought evidence that central reticular fibroblasts of nodular keloids are the population which synthesize higher levels of mature collagens, TGFß, HIF1α and αSMA as compared to control skin, suggesting that this central deep region is the nucleus of ECM production with a centrifuge extension in keloids. Although no significant variations were found for basal proliferation, migration of peripheral fibroblasts from extensive keloids was higher than that of central ones and from nodular cells. Moreover, these peripheral fibroblasts from extensive keloids exhibited higher traction forces than central cells, control fibroblasts and nodular ones. Altogether, studying fibroblast features demonstrate keloid heterogeneity, leading to a better understanding of keloid pathophysiology and treatment adaptation.
Subject(s)
Keloid , Humans , Keloid/metabolism , Skin/metabolism , Dermis/metabolism , Fibroblasts/metabolism , Collagen/metabolism , Cells, CulturedABSTRACT
Objectives: Limited data on performing bilateral pulmonary artery banding (BPAB) before stage 1 Norwood procedure suggest that some patients may benefit through the postponement of the major cardiopulmonary bypass procedure. The objective of this study was to evaluate the effectiveness of BPAB in the surgical management of high-risk patients with hypoplastic left heart syndrome (HLHS). Methods: A retrospective review of all high-risk neonates with HLHS who underwent BPAB at our institution was performed. No patients, including those with intact or highly restrictive atrial septum (IAS), were excluded. Results: Between October 2015 and April 2021, 49 neonates with HLHS (including 6 with IAS) underwent BPAB, 40 of whom progressed to the Norwood procedure. Risk factors for not progressing to the Norwood procedure after BPAP include low birth weight (P = .043), the presence of multiple extracardiac anomalies (P = .005), and the presence of genetic disorders (P = .028). Operative mortality was 7.5% (3/40). IAS was associated with operative mortality (P = .022). Conclusions: The strategy of BPAB prestage 1 Norwood procedure was successful in identifying at-risk patients and improving Norwood survival. Although not all patients will need this hybrid approach, a significant number can be expected to benefit from this tactic. These results support the need for a substantial hybrid strategy, in addition to a primary stage 1 Norwood surgical strategy, in the management of HLHS.
ABSTRACT
Basal/squamous (Ba/Sq) subtype represents an intrinsic and robust group in the consensus molecular classification of muscle-invasive bladder cancer (MIBC), with poor outcome and controversial chemosensitivity. We aimed to investigate the spectrum of intratumor heterogeneity (ITH) in the Ba/Sq subtype. First, we validated a 29-gene NanoString CodeSet to predict the Ba/Sq subtype for FFPE samples. We identified heterogeneous Ba/Sq tumors in a series of 331 MIBC FFPE samples using dual GATA3/KRT5/6 immunohistochemistry (IHC). Heterogeneous regions with distinct immunostaining patterns were studied separately for gene expression using the 29-gene CodeSet, for mutations by targeted next-generation sequencing, and for copy number alteration (CNA) by microarray hybridization. Among 83 Ba/Sq tumors identified by GATA3/KRT5/6 dual staining, 19 tumors showed heterogeneity at the IHC level. In one third of the 19 cases, regions from the same tumor were classified in different distinct molecular subtypes. The mutational and CNA profiles confirmed the same clonal origin for IHC heterogeneous regions with possible subclonal evolution. Overall, two patterns of intratumoral heterogeneity (ITH) were observed in Ba/Sq tumors: low ITH (regions with distinct immunostaining, but common molecular subtype and shared CNA) or high ITH (regions with distinct immunostaining, molecular subtype, and CNA). These results showed multilayer heterogeneity in Ba/Sq MIBC. In view of personalized medicine, this heterogeneity adds complexity and should be taken into account for sampling procedures used for diagnosis and treatment choice. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Subject(s)
Biomarkers, Tumor/genetics , DNA Copy Number Variations/genetics , Mutation/genetics , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/pathology , Biomarkers, Tumor/metabolism , Gene Expression Profiling/methods , Humans , Immunohistochemistry/methods , Precision Medicine/methods , Urinary Bladder Neoplasms/diagnosisABSTRACT
INTRODUCTION: Fentanyl pharmacokinetic and pharmacodynamic data are limited in mechanically ventilated children. This study aimed to assess the fentanyl pharmacokinetics (PK), the sedation outcome, and the development of tolerance in children receiving fentanyl continuous infusion. METHODS: This study included children admitted to the pediatric or cardiovascular intensive care unit between January 1 and October 31, 2016, who were >30 days to <18 years of age, receiving ventilatory support via endotracheal tube or tracheostomy, and receiving a fentanyl infusion. Population PK analysis was performed using a nonlinear mixed-effects model. The relationship between initial sedation outcome using State Behavioral Scale (SBS) and fentanyl exposure was assessed, and the observations consistent with tolerance were described. RESULTS: Seventeen children, with a median age of 0.83 years (range: 0.1-12) and weight of 8.7 kg (range: 3.4-52), were included. The fentanyl PK was adequately described by a weight-based allometry model with the power of 0.75 for clearance (CL=89.8 L/hr/70 kg) and distributional CL, and 1 for volumes of distribution. In infants <6.6 months, age was an additional factor for CL (31.4 L/h/70 kg) to account for age-related maturation. Seven of twelve nonparalyzed patients achieved goal sedation, defined as >80% of SBS scores ≤0 per 24 h, on the first day of fentanyl infusion with a median plasma concentration of 1.29 ng/ml (interquartile range: 0.78-2.05). Eight of the nine tolerant patients developed tolerance within a day of reaching goal sedation. CONCLUSION: Different weight-based fentanyl dosing rates may be required for infants and children of different ages to achieve similar plasma concentrations. Using SBS scores may guide the dosing titration of fentanyl that resulted in plasma concentrations within the therapeutic range of 1-3 ng/ml. For those who developed tolerance to fentanyl and/or a sedative, it was noted one day after goal sedation was achieved.
Subject(s)
Fentanyl , Child , Child, Preschool , Critical Illness , Drug Tolerance , Fentanyl/pharmacokinetics , Fentanyl/pharmacology , Humans , Hypnotics and Sedatives , Infant , Intensive Care Units , Respiration, ArtificialABSTRACT
OBJECTIVE: Although transcriptomic assessments of small samples using high-throughput techniques are usually performed on fresh or frozen tissues, there is a growing demand for those performed on stained cellular specimens already used for diagnostic purposes. STUDY DESIGN: The possibility of detecting mRNAs and microRNAs (miRNAs) from routinely processed cytological samples using nCounter® technology was explored. Fresh samples from pleural and peritoneal effusions were analyzed using 2 parallel methods: samples were smeared and routinely stained using the May-Grünwald-Giemsa or Diff-Quik® method and mounted using conventional methods, and they were also studied following a snap freezing method, in which samples were maintained at -80°C until use. mRNAs and miRNAs were assessed and compared after total RNA extraction from both routinely processed samples and their matched frozen controls. RESULTS: A good concordance was found between the gene expression measured in routinely processed samples and their matched frozen controls for the majority of mRNAs and miRNAs tested. However, the standard deviation of low-expressed miRNA was high. CONCLUSIONS: Although nCounter® technology is a robust method to measure and characterize both mRNAs and miRNAs from routinely processed cytological samples, caution is recommended for the interpretation of low-expressed miRNA.
Subject(s)
Cytological Techniques/methods , Gene Expression Profiling/methods , Gene Expression/genetics , MicroRNAs/genetics , RNA, Messenger/genetics , Azure Stains/chemistry , Eosine Yellowish-(YS)/chemistry , Humans , Methylene Blue/chemistry , Paraffin Embedding/methods , Proof of Concept Study , Xanthenes/chemistryABSTRACT
OBJECTIVES: To compare fentanyl infusion pharmacokinetic variables in obese children and nonobese children. DESIGN: A pharmacokinetic simulation study. SETTING: We used a semi-physiologically based pharmacokinetic model to generate fentanyl pharmacokinetic variables. SUBJECTS: Simulations of pharmacokinetic variables were based on historical inpatient demographic data in less than 18-year-olds. INTERVENTIONS: Obese children were defined as children less than 2 years with weight-for-length greater than or equal to 97.7th percentile or body mass index-for-age greater than or equal to 95th percentile for greater than or equal to 2-17-year-olds. MEASUREMENTS AND MAIN RESULTS: Overall, 4,376 patients were included, with 807 (18.4%) classified as obese children. The majority (52.9%) were male, with a median age of 8.1 years (interquartile range, 4.3-13.0 yr). The differences in total clearance (CLS), volume of distribution at steady-state values, weight-normalized CLS, and weight-normalized volume of distribution at steady state were assessed in obese children and nonobese children. Multivariable analyses indicated that obesity was significantly associated with a higher CLS in obese children greater than 6-year-olds (p < 0.0375). However, there was an 11-30% decrease in weight-normalized CLS in obese children versus nonobese children in all age groups (p < 0.05). Both volume of distribution at steady state and weight-normalized volume of distribution at steady state increased significantly in obese children compared with nonobese children (p < 0.05). Fentanyl plasma concentration-time profiles of obese children and nonobese children pairs (ages 4, 9, and 15) receiving 1 µg/kg/hr using total body weight were also compared. Steady-state concentrations of the obese children using similar weight-based dosing increased by 25%, 77%, and 44% in comparison to nonobese children 4-, 9-, and 15-year-olds, respectively. Time to steady state and elimination half-lives were two- to four-fold longer in obese children. An additional simulation was conducted for 15-year-old obese children and nonobese children using a fixed dose of 50 µg/hr and it provided similar pharmacokinetic profiles. CONCLUSIONS: CLS may increase less than proportional to weight in obese children greater than 6-year-olds, while volume of distribution at steady state increases more than proportional to weight in all obese children compared with nonobese children. Weight-based dosing in obese children may cause an increase in steady-state concentration while prolonging the time to steady state. Exploring alternative dosing strategies for obese children is warranted.
Subject(s)
Fentanyl/pharmacokinetics , Obesity/epidemiology , Adolescent , Body Mass Index , Child , Child, Preschool , Computer Simulation , Female , Fentanyl/administration & dosage , Humans , Male , Metabolic Clearance RateABSTRACT
People living with HIV (PLHIV) face specific issues regarding mental quality of life (QoL), in particular self-esteem. The objective of this study was to measure self-esteem and to identify associated factors among PLHIV in Morocco. A 125-item questionnaire was administered to 300 PLHIV. The dependent variable was adapted from Rosenberg's self-esteem scale (range 0-4). A weighted multiple linear regression was performed. The mean level of self-esteem was 2.4 ± 1.0. The factors independently associated with self-esteem were: feeling of loneliness (p = 0.001), perceived seriousness of infection (p = 0.006), thinking serostatus disclosure was a mistake (p = 0.007), thinking HIV infection will last for life (p = 0.008), sexual orientation (p = 0.050), satisfaction with sexual life (p = 0.019) and perceived treatment efficacy (p = 0.009). These results underline the need for evidence-based interventions (e.g. anti-discrimination measures, interventions to prevent social isolation of PLHIV, support in the serostatus disclosure process), in order to improve the social environment and eventually improve their self-esteem and QoL.
Subject(s)
HIV Infections/psychology , Self Concept , Adult , Attitude to Health , Cross-Sectional Studies , Female , Humans , Linear Models , Loneliness , Male , Morocco , Quality of Life/psychology , Self Disclosure , Surveys and QuestionnairesABSTRACT
OBJECTIVE: The objective of this study was to assess the short-term effects of Gundo-So-a program aimed at empowering Malian women living with HIV (WLHIV) regarding serostatus disclosure management. METHODS: A pre-experimental study with two measures (one week before and four weeks after Gundo-So) was carried out. A 35-item questionnaire was administered to a convenience sample of 210 WLHIV. Six outcomes were considered: ability to decide whether or not to disclose HIV status, self-efficacy to keep HIV status a secret, self-efficacy to disclose HIV status, feeling crushed by the weight of secrecy, perceived physical health, and perceived psychological health. For each outcome, temporal changes associated with the intervention were assessed using linear regressions with random intercepts. RESULTS: Statistically significant change was observed for all six outcomes between the pre- and post-intervention measures. Furthermore, several variables were associated with the baseline levels of the outcomes and the intervention effect. CONCLUSION: The results suggest that Gundo-So empowers Malian WLHIV with regard to serostatus disclosure management, thus improving their perceived physical and psychological health. PRACTICAL IMPLICATIONS: These results highlight the need for programs to empower WLHIV regarding serostatus disclosure, so that WLHIV can make free and informed decisions regarding serostatus disclosure.
Subject(s)
HIV Infections/psychology , HIV Seropositivity/psychology , Power, Psychological , Sexual Partners/psychology , Social Stigma , Truth Disclosure , Adult , Black People , Community-Based Participatory Research , Female , HIV Infections/ethnology , HIV Seropositivity/ethnology , Humans , Male , Mali , Program Evaluation , Self Disclosure , Self Efficacy , Social Support , Surveys and QuestionnairesSubject(s)
Anti-HIV Agents/therapeutic use , HIV Infections/prevention & control , Homosexuality, Male , Needs Assessment , Pre-Exposure Prophylaxis , Adult , Africa, Western/epidemiology , HIV Infections/epidemiology , Health Knowledge, Attitudes, Practice , Humans , Incidence , Male , Patient Acceptance of Health Care/statistics & numerical data , Pilot Projects , Pre-Exposure Prophylaxis/statistics & numerical data , Prospective Studies , Sex Workers/statistics & numerical data , Unsafe Sex/statistics & numerical data , Young AdultABSTRACT
Rocky Mountain spotted fever is a tick-borne illness that is prevalent in the south and the central United States, primarily during the summer months. Patients with delayed diagnosis can experience increased mortality and morbidity, particularly poor neurological outcome. We present a case of a 7-year-old girl with Rocky Mountain spotted fever who was admitted with severe neurological changes and septic shock on day 8 of illness. She was initially diagnosed with Kawasaki disease and treated with intravenous immunoglobulin. Her treatment also included doxycycline, vancomycin, and ceftriaxone due to concerns regarding Rocky Mountain spotted fever and bacterial sepsis. During hospitalization, the patient required mechanical ventilation for respiratory distress, inotropic support, and fluid resuscitation for hypotension. Titers for Rocky Mountain spotted fever were ultimately positive, with magnetic resonance imaging of the brain demonstrating numerous punctate foci of restricted diffusion within the supratentorium, including the corpus callosum and basal ganglia. Although the patient presented late in the disease course, she ultimately had a good neurological outcome. We theorized that administration of intravenous immunoglobulin prevented ongoing neurological injuries from the cerebral vasculitis, which are associated with Rocky Mountain spotted fever.
ABSTRACT
Recent reports have described increased risk of acute kidney injury (AKI) in adults receiving concomitant vancomycin and piperacillin/tazobactam, but few reports exist in children. We describe an 8-year-old girl who was admitted to the pediatric intensive care unit with respiratory distress secondary to pneumonia. She began treatment with vancomycin and piperacillin/tazobactam. She developed AKI, and piperacillin/tazobactam and vancomycin were discontinued. Following a furosemide infusion, her AKI resolved and serum creatinine returned to baseline. She later resumed piperacillin/tazobactam monotherapy for multidrug-resistant tracheitis with no evidence of AKI and was eventually discharged to a long-term care facility. The Naranjo probability scale supports a probable drug-related adverse event. Clinicians must be aware of the possibility of AKI with this combination and should monitor renal function and vancomycin concentrations vigilantly. Future prospective studies are needed to explore the incidence and clinical characteristics associated with AKI after this combination in children.
ABSTRACT
The sexuality of people living with HIV (PLHIV) is a key issue in the fight against HIV, as it influences both the dynamic of the epidemic and the quality of life of PLHIV. The present study examined the factors associated with cessation of sexual relations after HIV diagnosis among men and women in five countries: Mali, Morocco, Democratic Republic of the Congo, Romania and Ecuador. A community-based cross-sectional study was implemented by a mixed consortium [researchers/community-based organizations (CBO)]. Trained CBO members interviewed 1500 PLHIV in contact with CBOs using a 125-item questionnaire. A weighted multivariate logistic regression and a separate gender analysis were performed. Among the 1413 participants, 471 (33%) declared that they stopped having sexual relations after their HIV diagnosis, including 318 women (42%) and 153 men (23%) (p < .001). Concerning women, variables associated with the cessation of sexual relations in the final multivariate model were mainly related with relational factors and the possibility of getting social support (e.g., needing help to disclose HIV serostatus, feeling lonely every day, not finding support in CBOs, not being in a couple). Men's sexual activity was more associated with their representations and their perception of the infection (e.g., thinking they will have their HIV infection for the rest of their life, perceiving the HIV infection as a mystery, perceiving the infection as serious). Furthermore, the following variables were associated with both men and women sexual behaviours: being older, having suffered from serious social consequences after serostatus disclosure and not being able to regularly discuss about HIV with their steady partner. Results suggested clear differences between men and women regarding cessation of sexual relations and highlighted the importance of implementing gender-based tailored interventions that promote safe and satisfying sexuality, as it is known to have a positive impact on the overall well-being of PLHIV.
Subject(s)
HIV Seropositivity/psychology , Quality of Life/psychology , Sexual Behavior/statistics & numerical data , Sexuality , Social Support , Adult , Aged , Community-Based Participatory Research , Cross-Sectional Studies , Democratic Republic of the Congo , Ecuador , Emotions , Female , Humans , Logistic Models , Male , Mali , Morocco , Multivariate Analysis , Romania , Sex Factors , Sexual Behavior/psychology , Sexual Partners , Surveys and QuestionnairesABSTRACT
Hotspot mutations in the spliceosome gene SF3B1 are reported in â¼20% of uveal melanomas. SF3B1 is involved in 3'-splice site (3'ss) recognition during RNA splicing; however, the molecular mechanisms of its mutation have remained unclear. Here we show, using RNA-Seq analyses of uveal melanoma, that the SF3B1(R625/K666) mutation results in deregulated splicing at a subset of junctions, mostly by the use of alternative 3'ss. Modelling the differential junctions in SF3B1(WT) and SF3B1(R625/K666) cell lines demonstrates that the deregulated splice pattern strictly depends on SF3B1 status and on the 3'ss-sequence context. SF3B1(WT) knockdown or overexpression do not reproduce the SF3B1(R625/K666) splice pattern, qualifying SF3B1(R625/K666) as change-of-function mutants. Mutagenesis of predicted branchpoints reveals that the SF3B1(R625/K666)-promoted splice pattern is a direct result of alternative branchpoint usage. Altogether, this study provides a better understanding of the mechanisms underlying splicing alterations induced by mutant SF3B1 in cancer, and reveals a role for alternative branchpoints in disease.
Subject(s)
Alternative Splicing/genetics , Melanoma/genetics , Phosphoproteins/genetics , RNA Splice Sites/genetics , Ribonucleoprotein, U2 Small Nuclear/genetics , Uveal Neoplasms/genetics , Cell Line, Tumor , HEK293 Cells , Humans , Immunoblotting , Immunoprecipitation , Mutation , RNA Splicing Factors , Sequence Analysis, DNA , Sequence Analysis, RNAABSTRACT
Despite the widespread dissemination of HIV information through public awareness campaigns in Mali, disclosing seropositivity to one's steady sexual partner (SSP) remains difficult for people living with HIV (PLHIV). Disclosure is a public health concern with serious implications and is also strongly linked to the quality of life of PLHIV. This study aimed to analyse factors associated with voluntary HIV disclosure to one's SSP, using a community-based cross-sectional study on 300 adult PLHIV in contact with a Malian community-based organization working in the field of AIDS response. A 125-item questionnaire was administered by trained personnel to study participants between May and October 2011. Analysis was restricted to the 219 participants who both reported having a SSP and answered to the question on disclosure to their SSP. A weighted multivariate logistic regression was used to determine variables independently associated with disclosure. In total, 161 participants (73%) reported HIV disclosure to their SSP. Having children (odds ratio [95% confidence interval]: 4.52 [1.84-11.12]), being accompanied to the survey site (3.66 [1.00-13.33]), knowing others who had publicly declared their seropositivity (3.12 [1.59-6.12]), having higher self-esteem (1.55 [1.09-2.19]) and using means other than anti-retroviral treatment to treat HIV (0.33 [0.11-1.00]) were independently associated with disclosure. This study identified several factors that should be considered for the design of interventions aimed at facilitating disclosure if/when desired in this cultural context.
Subject(s)
Disclosure , HIV Infections/psychology , HIV Seropositivity/psychology , Sexual Partners , Adult , Confidentiality , Cross-Sectional Studies , Female , HIV Infections/epidemiology , HIV Seropositivity/epidemiology , HIV Seropositivity/ethnology , Humans , Male , Mali/epidemiology , Quality of Life , Surveys and QuestionnairesABSTRACT
RATIONALE: HIV serostatus disclosure is a complex challenge for persons living with HIV (PLHIV). Despite its beneficial effects, it can also lead to stigmatization and rejection. The current lack of multi-dimensional measurement tools impede an in-depth understanding of the dynamic of disclosure. OBJECTIVE: To develop and validate complex measures of serostatus disclosure. METHODS: This international community based research study was performed by joint research teams (researchers/community based organizations (CBO)) in five countries (Democratic Republic of the Congo, Ecuador, Mali, Morocco and Romania). A convenience sample of 1500 people living with HIV (PLHIV) in contact with local CBO were recruited in 2011 (300 in each country). Face-to-face interviews were performed using a 125-item questionnaire covering HIV status disclosure to 23 potential disclosure targets and related issues (including personal history with HIV, people's reaction to disclosure, sexuality). A principal component analysis and a hierarchical cluster analysis were performed, in order to identify the main components of HIV disclosure, create measures and classify participants into profiles. RESULTS: Patterns of disclosure were summarized using two main measures: direct and indirect disclosure. Disclosure to sexual partners, whether steady or not, was different from patterns of disclosure to other targets. Among the participants, three profiles emerged - labelled Restricted disclosure, Mainly indirect disclosure and Mainly direct disclosure, respectively representing 61%, 13% and 26% of the total sample. The profiles were associated with different aspects of PLHIV's lives, including self-efficacy, functional limitations and social exclusion. Patterns varied across the five studied countries. CONCLUSION: Results suggest that multi-dimensional constructs should be used to measure disclosure in order to improve understanding of the disclosure process.