Machine learning outperformed logistic regression classification even with limit sample size: A model to predict pediatric HIV mortality and clinical progression to AIDS

Logistic regression (LR) is the most common prediction model in medicine. In recent years, supervised machine learning (ML) methods have gained popularity. However, there are many concerns about ML utility for small sample sizes. In this study, we aim to compare the performance of 7 algorithms in the prediction of 1-year mortality and clinical progression to AIDS in a small cohort of infants living with HIV from South Africa and Mozambique. The data set (n = 100) was randomly split into 70% training and 30% validation set. Seven algorithms (LR, Random Forest (RF), Support Vector Machine (SVM), K-Nearest Neighbor (KNN), Naive Bayes (NB), Artificial Neural Network (ANN), and Elastic Net) were compared. The variables included as predictors were the same across the models including sociodemographic, virologic, immunologic, and maternal status features. For each of the models, a parameter tuning was performed to select the best-performing hyperparameters using 5 times repeated 10-fold cross-validation. A confusion-matrix was built to assess their accuracy, sensitivity, and specificity. RF ranked as the best algorithm in terms of accuracy (82,8%), sensitivity (78%), and AUC (0,73). Regarding specificity and sensitivity, RF showed better performance than the other algorithms in the external validation and the highest AUC. LR showed lower performance compared with RF, SVM, or KNN. The outcome of children living with perinatally acquired HIV can be predicted with considerable accuracy using ML algorithms. Better models would benefit less specialized staff in limited resources countries to improve prompt referral in case of high-risk clinical progression

Caractérisation des bases moléculaires de la résistance des virus de l'immunodéficience humaine de type 1 ( VIH-1) de sous-type non-B aux antirétroviraux

Grâce aux traitements antirétroviraux le Sida est devenu une maladie chronique. Un des défis de la lutte contre le VIH/SIDA est de caractériser la résistance développée par le VIH aux ARV. Or, les connaissances portent essentiellement sur le sous-type B du VIH-1 circulant majoritairement dans les pays industrialisés. Ainsi, il est important d étudier les bases moléculaires de la résistance du VIH-1 de sous-type non-B avec l accès de plus en plus important aux ARV au Sud. Le premier travail a évalué l efficacité d une première ligne Triomune® d4T/3TC/NVP chez l adulte, lors d un échec virologique précoce. Cette étude a montré que lors d un échec précoce nous avons des profils de mutation au 3TC (M184V) et aux INNTI (K103N et Y181C). La deuxième partie a consisté en la mesure de la prévalence de la résistance primaire, ainsi qu en la caractérisation des sous-types de VIH-1 circulant au Mali et nous avons obtenu une prévalence de 11,5%. La troisième partie a étudié la barrière génétique à la résistance des inhibiteurs d integrase vis-à-vis des sous-types B et CRF02_AG et l évaluation de la prévalence des mutations associées à la résistance à l ETR chez patients infectés par des VIH-1 de sous-types non-B et naïfs d ARV. Ces deux sous-types (B et CRF02_AG) présentent une barrière génétique similaire, mais on note une barrière génétique plus élevée pour le CRF02_AG aux positions 140 et 151 de l integrase. Nous avons obtenu 10% de virus portant des mutations de résistance à l ETR chez patients infectés par des sous-types non-B et naïfs d ARV. Ces données sont importantes à prendre en compte pour l établissement des 2èmes et 3èmes lignes de traitement ARV dans les pays du Sud.PARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Re-engagement in care of people living with HIV lost to follow-up after initiation of antiretroviral therapy in Mali: Who returns to care?

International audienc

Risk factors for loss to follow-up, transfer or death among people living with HIV on their first antiretroviral therapy regimen in Mali

International audienceOBJECTIVES: Risk factors for loss to follow-up (LTFU) were assessed for people living with HIV (PLHIV) at various reference out-patient clinics (expertise level II) and hospitals (expertise level III) in Mali.METHODS: HIV-1-positive adults starting antiretroviral therapy (ART) in 2006-2013 were eligible for inclusion. Risk factors for LTFU, defined as no visit in the 6 months preceding the last database update, were assessed with the Cox model, taking into account the competing risks of transfer and death. Potential risk factors at the start of ART were demographic and socioeconomic variables, World Health Organization (WHO) stage, CD4 count, period of ART initiation, type of ART, region of care, expertise level and distance from home.RESULTS: We included 9821 PLHIV, 33% of whom were male, starting ART at nine out-patient clinics and seven hospitals [five and two in the capital Bamako and four and five in the 'regions' (i.e. districts outside the capital), respectively] with a median (interquartile range) CD4 count of 153 (56-270) cells/μL. Five-year cumulative incidences of LTFU, transfer and death were 35.2, 9.7 and 6.7%, respectively. People followed at Bamako hospitals > 5 km from home, at regional hospitals or at regional out-patient clinics < 5 km from home were at higher risk of LTFU than people followed at Bamako out-patient clinics, whereas people followed at regional out-patient clinics 5-50 km away from home were at lower risk for LTFU. Deaths were less frequent at hospitals, whether in Bamako or in the regions, than at Bamako out-patient clinics, and more frequent at regional out-patient clinics.CONCLUSIONS: Expertise level and distance to care were associated with LTFU. Stigmatization may play a role for PLHIV living close to the centres in the regions

Very high prevalence of extended-spectrum beta-lactamase-producing Enterobacteriaceae in bacteriemic patients hospitalized in teaching hospitals in Bamako, Mali.

The worldwide dissemination of extended-spectrum beta-lactamase producing Enterobacteriaceae, (ESBL-E) and their subset producing carbapenemases (CPE), is alarming. Limited data on the prevalence of such strains in infections from patients from Sub-Saharan Africa are currently available. We determined, here, the prevalence of ESBL-E/CPE in bacteriemic patients in two teaching hospitals from Bamako (Mali), which are at the top of the health care pyramid in the country. During one year, all Enterobacteriaceae isolated from bloodstream infections (E-BSI), were collected from patients hospitalized at the Point G University Teaching Hospital and the pediatric units of Gabriel Touré University Teaching Hospital. Antibiotic susceptibility testing, enzyme characterization and strain relatedness were determined. A total of 77 patients had an E-BSI and as many as 48 (62.3%) were infected with an ESBL-E. ESBL-E BSI were associated with a previous hospitalization (OR 3.97 95% IC [1.32; 13.21]) and were more frequent in hospital-acquired episodes (OR 3.66 95% IC [1.07; 13.38]). Among the 82 isolated Enterobacteriaceae, 58.5% were ESBL-E (20/31 Escherichia coli, 20/26 Klebsiella pneumoniae and 8/15 Enterobacter cloacae). The remaining (5 Salmonella Enteritidis, 3 Morganella morganii 1 Proteus mirabilis and 1 Leclercia adecarboxylata) were ESBL negative. CTX-M-1 group enzymes were highly prevalent (89.6%) among ESBLs; the remaining ones being SHV. One E. coli produced an OXA-181 carbapenemase, which is the first CPE described in Mali. The analysis of ESBL-E relatedness suggested a high rate of cross transmission between patients. In conclusion, even if CPE are still rare for the moment, the high rate of ESBL-BSI and frequent cross transmission probably impose a high medical and economic burden to Malian hospitals

Genetic relatedness (Rep-PCR) between ESBL producing <i>Enterobacteriaceae</i> isolated from bacteriemic patients hospitalized in referral centers in Bamako (Mali).

<p>(a) ESBL-producing <i>E</i>. <i>coli</i>, n = 20. (<b>b</b>) ESBL-producing <i>K</i>. <i>pneumonia</i>, n = 20 and (<b>c</b>) ESBL-producing <i>E</i>. <i>cloacae</i>, <i>n = 8</i>. PG = Point G University teaching hospital (adults), GT = Gabriel Touré University teaching hospital (pediatric).</p

Antibiotic resistance rate of <i>Enterobacteriaceae</i> isolated from bloodstream infections.

<p>Antibiotic resistance rate of <i>Enterobacteriaceae</i> isolated from bloodstream infections.</p

Risks factor for ESBL producing <i>Enterobacteriaceae</i> bloodstream infections.

<p>Risks factor for ESBL producing <i>Enterobacteriaceae</i> bloodstream infections.</p

Characterization of Drug Resistance and the Defective HIV Reservoir in Virally Suppressed Vertically Infected Children in Mali

Abstract Background In the perspective of ART-free HIV remission, vertically infected children treated with suppressive ART from early infancy represent an optimal population model to better understand the genetic complexity of the reservoir. Objectives To evaluate the proportion of defective viral population and the genotypic resistance patterns in cell-associated HIV DNA. Methods In a cohort including 93 ART-treated vertically HIV-infected (VHIV) children in Mali with plasma HIV-1 RNA ≤q50\,copies/mL for at least 6\,months, we studied total HIV DNA, percentage of defective genomes and resistance by reverse transcriptase and protease bulk sequencing from whole blood in dried blood spots. Results Children had a median age of 9.9\,years at the time of inclusion (IQR\,=\,7.6\textendash 13.4) and 3.3\,years (IQR\,=\,2\textendash 7) at ART initiation; median ART duration was 5.5\,years (IQR\,=\,3.7\textendash 7.3). The median level of total HIV DNA was 470\,copies/106\,cells with one patient presenting undetectable HIV DNA (&lt;66\,copies/106\,cells). We observed the presence of at least one stop codon in viruses from 34 patients (37%). The presence of stop codons was not correlated with the level of HIV DNA or duration of ART. We showed a high prevalence of HIV-1 resistance in DNA with 26% of children harbouring virus resistant to at least one NRTI and 40% to at least one NNRTI. Conclusions While these VHIV children were successfully treated for a long time, they showed high prevalence of resistance in HIV DNA and a moderate defective HIV reservoir