Valeur diagnostique de deux tests rapides utilisés dans le diagnostic du VIH-2 au Mali : Diagnosis value of two HIV-2 rapid diagnostic tests used in Mali

Context and objective. In sub-Saharan Africa, the epicenter of HIV infection, rapid tests are proposed in first line, but diagnosis value of these tests is rarely performed. The goal of the present study was to evaluate the performance of 2 rapid tests used for the diagnosis of HIV-2 infection compared to a baseline test in order to propose in algorithm for HIV infection diagnosis in health care system. Methods. A cross-sectional study was carried out in three treatment centers in Mali (Bamako, Segou and Sikasso). The tests evaluated were: Genie® II HIV-1/HIV-2 (Sanofi Diagnostic Pasteur, France) and ImmunoComb® II HIV 1&2 BiSpot (Organics, Strasbourg, France). The study involved 34 sera collected consecutively. The l’INNO-LIA HIV I/II Score confirmatory test was used as a reference test in Belgium. Performance of tests were assessed using sensibility, specificity, positive predictive value, negative predictive value and kappa concordance. Results. Patients’ ages ranged from 12 years to 78 years, 19 patients were women (55.8%) and 28 patients had HIV-2 infection. The sensitivity of the rapid tests was 96.4%. The kappa concordance coefficient was 0.85. We found 28 HIV-2 positive patients out of 34 patients. Conclusions. The two rapid tests used in Mali yielded satisfactory results, but the quality of HIV-1 and 2 discrimination serology could be improved. Contexte et objectif. Dans les pays d’Afrique subsaharienne épicentre de l’infection à VIH, les tests rapides sont proposés en première intention, mais la valeur diagnostique de ces tests est rarement réalisée. L’objectif du présent travail était d’évaluer la performance de 2 tests rapides utilisés pour le diagnostic de l’infection à VIH-2 par rapport un test de référence afin de proposer des algorithmes de tests simples et rapides utilisables dans les structures sanitaires. Méthodes.Une étude transversale a été réalisée, dans trois centres de prise en charge au Mali (Bamako, Ségou et Sikasso). Les tests évalués étaient le Genie® II HIV-1/HIV-2 (Sanofi Diagnostic Pasteur, France) et l’ImmunoComb® II HIV 1&2 BiSpot (Organics, Strasbourg, France). L’étude a porté sur 34 sérums collectés consécutivement. Le test de confirmation l’INNO-LIA HIV I/II Score a été utilisé comme test de référence en Belgique. La performance de deux tests précités a été évaluée en recherchant la sensibilité, la spécificité, la valeur prédictive positive (VPP), la valeur prédictive négative (VPN) et la concordance. Résultats. L’âge des patients variait de 12 ans à 78 ans, 19 patients étaient des femmes (55,8%) et 28 patients avaient le VIH-2. La sensibilité des tests rapides était de 96,4%. Le coefficient de concordance kappa était de 0,85. Conclusions. Les deux tests rapides utilisés au Mali ont donné des résultats satisfaisants, et peuvent être proposés en première intention dans l’algorithme national du diagnostic de l’infection à VIH-2 au Mali

Polymorphisms of HIV-2 integrase and selection of resistance to raltegravir

<p>Abstract</p> <p>Background</p> <p>Human Immunodeficiency Virus type 2 is naturally resistant to some antiretroviral drugs, restricting therapeutic options for patients infected with HIV-2. Regimens including integrase inhibitors (INI) seem to be effective, but little data on HIV-2 integrase (IN) polymorphisms and resistance pathways are available.</p> <p>Materials and methods</p> <p>The <it>integrase </it>coding sequence from 45 HIV-2-infected, INI-naïve, patients was sequenced and aligned against the ROD (group A) or EHO (group B) reference strains and polymorphic or conserved positions were analyzed.</p> <p>To select for raltegravir (RAL)-resistant variants <it>in vitro</it>, the ROD strain was cultured under increasing sub-optimal RAL concentrations for successive rounds. The phenotype of the selected variants was assessed using an MTT assay.</p> <p>Results</p> <p>We describe <it>integrase </it>gene polymorphisms in HIV-2 clinical isolates from 45 patients. Sixty-seven percent of the integrase residues were conserved. The HHCC Zinc coordination motif, the catalytic triad DDE motif, and AA involved in IN-DNA binding and correct positioning were highly conserved and unchanged with respect to HIV-1 whereas the connecting residues of the N-terminal domain, the dimer interface and C-terminal LEDGF binding domain were highly conserved but differed from HIV-1. The N155 H INI resistance-associated mutation (RAM) was detected in the virus population from one ARV-treated, INI-naïve patient, and the 72I and 201I polymorphisms were detected in samples from 36 and 38 patients respectively. No other known INI RAM was detected.</p> <p>Under RAL selective pressure <it>in vitro</it>, a ROD variant carrying the Q91R+I175M mutations was selected. The Q91R and I175M mutations emerged simultaneously and conferred phenotypic resistance (13-fold increase in IC₅₀). The Q91R+I175M combination was absent from all clinical isolates. Three-dimensional modeling indicated that residue 91 lies on the enzyme surface, at the entry of a pocket containing the DDE catalytic triad and that adding a positive charge (Gln to Arg) might compromise IN-RAL affinity.</p> <p>Conclusions</p> <p>HIV-2 polymorphisms from 45 INI-naïve patients are described. Conserved regions as well as frequencies of HIV-2 IN polymorphisms were comparable to HIV-1. Two new mutations (Q91R and I175M) that conferred high resistance to RAL were selected <it>in vitro</it>, which might affect therapeutic outcome.</p

Antiretroviral-induced adverse drug reactions in HIV-infected patients in Mali: a resource-limited setting experience

Background: There are few reports in the literature from sub-Saharan Africa (SSA) regarding antiretroviral-induced adverse drug reactions (ADRs). Antiretroviral therapy (ART) is now widely available in SSA, and ADRs during HIV infection are also frequent. In this study, we reported the frequency and risk factors of ART-induced ADRs in a Malian population.Methods: This prospective cohort study was performed in the HIV Care and Counseling Centre (CESAC) of Mali from 2011 to 2012. Adult patients infected with HIV and who had recently started ART were included and followed-up clinically Were included in this study, adult patients living with HIV and had recently started ART who were followed up for at least 6 months to determine the incidence of ADRs using Naranjo’s classification scale.Results: During this study, 357 (42.3%) patients presented ADRs (40.1% of our patients (n=338) experienced at least one ADR, and 2.2% (n=19) experienced at least two ADRs). The prevalence of ADRs by organ system was: 45.9% neurological (n=164); 29.4% metabolic (blood chemistry) (n=105); 15.4% hematological (n=55). High probable rate of ADR was observed as indicated by the Naranjo score in 83.7% of the cases. Zidovudine (AZT) and stavudine (d4T) use was identified as a risk factor for either anaemia or peripheral neuropathy whereas nevirapine (NVP) and female gender were risk factors for skin reactions. Patients with advance disease had the highest rate of ADRs compared to the others.Conclusions: Based on the Naranjo probability scale, our data show that ADRs such as peripheral neuropathy and anemia are very frequent. These ADR was linked to AZT and D4T. Our findings highlight the need for active monitoring, continuous pharmacovigilance of ART and change of some ART drug in this population

Risk management of adverse effects of antimalarial drugs: Knowledge of Physicians and Pharmacists in KAYES, MALI

In order to improve therapeutic compliance and prevent antimalarial drug resistance, we conducted this study to evaluate the knowledge of physicians and pharmacists in Kayes on the management of adverse effects of antimalarial drugs. Methods: A cross-sectional study was conducted from July to November 2017 among physicians and pharmacists selected by simple random sampling and practicing in the Kayes region for more than one year. The survey was based on a questionnaire proposed by the national pharmacovigilance center. In addition to a descriptive analysis of the results, a logistic regression analysis was performed to assess potential factors that could be associated with knowledge. Results: Among 151 physicians and pharmacists participated in the study, less than 40% had better knowledge about the management of antimalarial drug adverse events. Physicians and pharmacists working in government facilities were more likely to have better knowledge compared with those working in other facilities (OR=8.38; 95% CI: 2.48-28.30). In addition, pharmacists were more likely to have better knowledge than physicians (OR=3.48; 95% CI: 1.21-12.19). Conclusions: The frequency of good knowledge of the management of adverse drug reactions to antimalarials is insufficient, although membership in government structures and profession seem likely to improve it

Planification familiale et IST/VIH : connaissances et pratiques des adolescents du lycée Monseigneur Luc Sangaré de Bamako

Notre étude a porté sur 330 adolescents du Lycée Monseigneur Luc Sangaré de Bamako. Il s’agissait d’une étude transversale prospective de 3 mois allant du 02 janvier au 30 Mars 2007. L’objectif général était d’étudier le comportement des élèves dudit lycée sur la planification familiale et les connaissances sur les IST/VIH. Ont été inclus à cette étude les élèves des deux sexes inscrits pour l’année 2006-2007 et ayant donné leur consentement. Un questionnaire a été donné à chacun des participants afin de recueillir des informations sur la connaissance de la planification familiale et des IST /VIH. Nous avons constaté que la presque la totalité des élèves avait déjà entendu parler de la planification familiale, soit 99,4% ; 97,3% l’associent à l’espacement de naissance. Les méthodes contraceptives les plus connues étaient le préservatif (97,9%), la pilule (72,4%). Quant aux IST, le VIH (99,7%) et la gonococcie (46,1%) ont été les plus cités ; 83,3% des élèves savaient que le VIH se transmet par l’usage de seringues souillées et 76,4% par voie sexuelle. L’utilisation du préservatif (92,4%) a été le moyen de prévention le plus répandu. Les principales sources d’information ont été les médias et les amis. L’information ne venait pas des parents. Malgré leur connaissance sur les IST-VIH, la plupart des adolescents n’ont pas eu recours aux préservatifs lors de leur premier rapport sexuel alors que 32,7% des élèves avaient un comportement à risque élevé

Suivi thérapeutique pharmacologique des antirétroviraux chez les femmes allaitantes au Mali : étude pilote

Objectif : La transmission mère-enfant du VIH durant l’allaitement est un problème de santé publique. Le but de cette étude était d’évaluer l’intérêt du suivi thérapeutique pharmacologique des femmes allaitantes sous ARV et leurs enfants à Bamako. Méthodes : Les patientes ont été recrutées du 1er septembre 2015 au 30 septembre 2016 suite à l’obtention de leur consentement éclairé. Les mères et leur enfant ont été suivis dans le service de pédiatrie du CHU Gabriel Touré. Les charges virales plasmatiques ont été réalisées à l’UCRC de Bamako. La détermination des concentrations  plasmatiques   des médicaments  a été  réalisée au laboratoire de Pharmacocinétique de Toulouse. Les données ont été saisies et analysées sur le logiciel SPSS version 20. Résultats : L’âge moyen des mères était de 29ans±75 [19-41ans]. A J0, une seule des patientes avait une charge virale plasmatique détectable soit 3,33%(6610copies/ml) et 73,91% des mères avaient un taux de CD4 supérieur à350cellules/mm3. Après 6mois, nous avions trouvé 3 mères qui avaient une charge virale détectable (200copies/ml ; 72copies/ml et 4777 copies/ml) et 86,36% des mères avaient un taux de CD4 supérieur à350cellules/mm3. Les concentrations plasmatiques médianes mères du lopinavir, de l’efavirenz à 3 mois étaient respectivement de 5770ng/ml ; 3505ng/ml et à 6 mois de 5850ng/ml ; 3245ng/ml.  Tous les nourrissons avaient une PCR négative à 3 mois et 6 mois de suivi. Conclusion : La mesure des paramètres biologiques constitue un maillon essentiel dans la prise en charge des femmes allaitantes VIH positif au Mali

Adverse Drug Reactions to Antiretroviral Therapy (ART): Prospective Study in HIV Infected Adults in Sikasso (Mali)

Objective: The purpose of this study was to evaluate the adverse effects of Antiretroviral Therapy (ART) in adult HIV-infected patients in decentralized setting of Sikasso, in Mali. Methods: This is a proactive study that took place from 2 January 2011 to 30 December 2012 at the Hospital of Sikasso (Department of Medicine). HIV-infected adult patients who have started ART at least 3 months before were included in this study to monitor the laboratory and clinical Adverse Drug Reactions (ADR) for at least 6 months. The WHO classification of adverse drug reactions has been used to investigate the causality of antiretrovirals. Results: Women were the most represented with 58% of the cases. The most represented age range was 26-47 years with 73.6%. Of the 178 patients enrolled, 61.2% had an ADR. ADR were neurological (40.4%), digestive (35.8%), cutaneous (18.3%) and hematological (5.5%). Stavudine was the most incriminated molecule, in 24.8% of the cases. The WHO grade 4 classification of ART toxicity was represented in 3.4% of the cases. The WHO causality score of “certain” was found in 29.8% of the cases. Conclusion: Adverse effects of Antiretrovirals are frequent and could be life-threatening in short and long terms. Regular follow-up of patients receiving these triple therapies, and the associated complications, is essential. We recommend active surveillance of antiretroviral therapy to strengthen Pharmacovigilance in Mali