Phenotypic properties of envelope glycoproteins of transmitted HIV-1 variants from patients belonging to transmission chains.

OBJECTIVE: Transmission of HIV-1 involves a bottleneck in which generally a single HIV-1 variant from a diverse viral population in the transmitting partner establishes infection in the new host. It is still unclear to what extent this event is driven by specific properties of the transmitted viruses or the result of a stochastic process. Our study aimed to better characterize this phenomenon and define properties shared by transmitted viruses. DESIGN: We compared antigenic and functional properties of envelope glycoproteins of viral variants found during primary infection in 27 patients belonging to eight transmission chains. METHODS: We generated pseudotyped viruses expressing Env variants of the viral quasispecies infecting each patient and compared their sensitivity to neutralization by eight human monoclonal broadly neutralizing antibodies (HuMoNAbs). We also compared their infectious properties by measuring their infectivity and sensitivity to various entry inhibitors. RESULTS: Transmitted viruses from the same transmission chain shared many properties, including similar neutralization profiles, sensitivity to inhibitors, and infectivity, providing evidence that the transmission bottleneck is mainly nonstochastic. Transmitted viruses were CCR5-tropic, sensitive to MVC, and resistant to soluble forms of CD4, irrespective of the cluster to which they belonged. They were also sensitive to HuMoNAbs that target V3, the CD4-binding site, and the MPER region, suggesting that the loss of these epitopes may compromise their capacity to be transmitted. CONCLUSION: Our data suggest that the transmission bottleneck is governed by selective forces. How these forces confer an advantage to the transmitted virus has yet to be determined

Les kystes hydatiques du foie rompus dans les voies biliaires à propos de 98 cas experience de la clinique chirurgicale "a"

Introduction : L’hydatidose hépatique encore fréquente au Maroc est une maladie réputée bénigne mais qui peut devenir grave à cause de ses complications. La rupture dans les voies biliaires constitue un tournant évolutif de la maladie qui d’hépatique devient hépato-biliaire et risque de mettre en jeu le pronostic vital. Le but de notre travail est de mieux cerner le traitement chirurgical de cette affection. Matériel et méthodes : C’est une étude rétrospective réalisée dans la Clinique Chirurgicale A de l’hôpital Ibn Sina de Rabat, qui porte sur 98 cas de KHF rompus dans les voies biliaires parmi les 478 cas de KHF opérés soit une fréquence de 20,5% et s’étend sur une période de 11 années allant de Janvier 1995 à décembre 2006. Notre travail a été mené grâce aux dossiers médicaux, aux comptes rendus opératoires, aux registres des entrants sortants ainsi qu’aux consultations ultérieures de suivi. Résultats : Nos patients se répartissent en 50 femmes et 48 hommes et sont âgés de 15 à 74 ans avec un âge moyen de 34,8 +/- 14,68. L’origine de nos patients était en majorité rurale et la notion de contact avec les chiens a été retrouvée dans 31,6% des cas. Le tableau clinique était marqué dans la majorité des cas par une association faite de douleur (78,5%), d’ictère (26,5%), de syndrome fébrile (28,6%) et d’épisodes d’angiocholite dans 9,2% des cas. L’examen clinique retrouve une HMG dans 25,5% des cas. La fistule kysto-biliaire était asymptomatique, découverte fortuitement dans 56,1% des cas. L’apport des examens radiologiques notamment l’échographie est très précieux, complétée par la tomodensitométrie si elle est douteuse, en effet, l’échographie a permis de montrer des signes indirects de rupture kysto-biliaire dans 19 cas soit 20,2% des cas, tandis que le scanner, réalisé pour 16 patients, a permis de poser le diagnostic de rupture du KHF dans les VB dans 8 cas soit 50% des cas. Cependant, le diagnostic de certitude des FKB ne peut être obtenu qu’en per-opératoire, grâce à un examen minutieux du fond de la cavité kystique et à la cholangiographie per-opératoire qui doit être systématique. Le traitement avait pour but l’élimination du parasite, la suppression de la cavité résiduelle et le traitement des lésions biliaires. Le traitement du kyste a consisté en un traitement radical dans 10 cas : la lobectomie gauche dans 6 cas, droite dans 2 cas, 1 cas de segmentectomie et un cas de périkystectomie totale. On a eu recours au traitement conservateur dans la majorité des cas, il s’agissait dans 74,5% des cas d’une résection du dôme saillant, d’une périkystectomie partielle dans 5,1% des cas, une ponction évacuation dans 7,2% des cas. Ce traitement conservateur a été complété par un aveuglement de la fistule biliaire dans 66,3%, un cathétérisme de la fistule dans 4,1% des cas, une cholédocostomie trans-hépatico kystique selon PERDOMO dans 7,2% des cas, un drainage de la VBP dans 9 cas, un drainage bipolaire dans 2 cas et enfin un cas d’anastomose bilio-digestive. Les suites post opératoires étaient simples dans 77,6% des cas, alors que 20,4% des patients ont présenté une ou plusieurs complications dominées par les fistules biliaires externes retrouvées dans 14,3% des cas. La majorité des complications survenues ont fait suite à un traitement conservateur. Cette morbidité occasionne une durée de séjour post opératoire moyenne de 12 jours, plus longue pour les cas traités par techniques conservatrices : 17 jours contre 12,8 jours en cas de traitement radical. Discussion : Les résultats obtenus dans notre série comparés aux données de la littérature suggèrent que les méthodes conservatrices, surtout la suture de la FKB après RDS sont à l’origine de morbidité précoce et d’hospitalisation prolongée mais dans les pays à forte endémie, c’est la RDS qui est la technique la plus utilisée vu sa simplicité. Ces méthodes constituent une alternative lorsque les méthodes radicales ne sont pas réalisables. Nos résultats rejoignent les constatations des auteurs quant à l’innocuité et l’efficacité des méthodes radicales dans le traitement des KHF rompus dans les VB, cependant, ces techniques ne sont pas de pratique courante vu la bénignité de cette affection et son endémicité. Conclusion : La rupture du KHF dans les voies biliaires demeure une complication fréquente et redoutable. La prophylaxie ainsi que le dépistage et le traitement de l’hydatidose à un stade précoce, contribueraient à la réduction de l’incidence de cette complication

HIV transmission network analysis allows identifying unreported risk factors in HIV-positive blood donors in France.

ObjectivesAs sex between men is a major route of human immunodeficiency virus (HIV) infection in most western countries, restrictive deferral rules for blood donation have largely been implemented regarding men having sex with men (MSM). Here, we sought here to assign unreported HIV risk factors in blood donors (BDs) and reevaluated the MSM-associated fraction of HIV transfusion residual risk (%RRMSM ).MethodsWe applied a genetic distance-based approach to infer an HIV transmission network for 384 HIV sequences from French BDs and 1337 HIV sequences from individuals with known risk factors (ANRS PRIMO primary HIV infection cohort). We validated the possibility of assigning a risk factor according to clustering using assortative mixing. Finally, we recalculated the %RRMSM .ResultsA total of 81 of 284 (28.5%) male and 5 of 100 (5%) female BDs belonged to a cluster; 72 (88.9%) of the 81 male BDs belonged to MSM clusters. After cluster correction, 8 of 67 (11.9%), 4 of 21 (19.0%), and 19 of 88 (21.6%) HIV-positive (HIV+) male BDs with heterosexual, other, or unknown risk factors could be reclassified as MSM, accounting for 10.9% of the total HIV+ male BDs. Overall, 139 of 284 HIV+ male donors (48.9%) could be considered MSM between 2000 and 2016 in France. Between 2005 and 2016, the %RRMSM increase varied from 0 to 19%, without differing significantly from the %RRMSM before reclassification.ConclusionNetwork inference can be used to complement declaration data on risk factors for HIV infection in BDs. This approach, complementary to behavioral studies, is a valuable tool to evaluate the effect of changes in deferral criteria on BD compliance

Immunoblots may not be effective in confirming the recency of HIV-1 infection

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Immunoblots may not be effective in confirming the recency of HIV-1 infection

International audienceRecently, immunoblots (IBs) have tended to substitute Western blots (WBs) for HIV infection diagnosis. Several studies have confirmed IBs' high sensitivity to confirm HIV infection for every stage. Since the nature and pattern of the antigens of IBs are different from those of WB, the abilities of IBs and WBs to distinguish the stages of recent seroconversion and open-ended chronic infection might differ. We aimed to evaluate the performance of two IBs (INNO-LIA™ HIVI/II, Fujirebio, and Geenius™ HIV1/2 Confirmatory assay, Bio-Rad) to define the stage of infection. We studied 53 patients from the French ANRS CO6 PRIMO cohort. IBs have higher positive rates than WB. However, Geenius was less sensitive than WB and INNO-LIA to detect antibodies to p31 (0% vs 22.6 % and 15.1 %, respectively), so it could wrongly label late Fiebig stage and open-ended chronic infections as recent infections (n = 5/53). For the first time, we provide evidence that centralized WBs associated with an enzyme immunoassay for the identification of recent HIV-1 infection support the establishment of a more accurate diagnosis of primary HIV infection to improve the accuracy of enrollments in cohorts of recent HIV infections useful for epidemiological studies, pathogenesis studies or therapeutic trials

Immunoblots may not be effective in confirming the recency of HIV-1 infection

International audienceRecently, immunoblots (IBs) have tended to substitute Western blots (WBs) for HIV infection diagnosis. Several studies have confirmed IBs' high sensitivity to confirm HIV infection for every stage. Since the nature and pattern of the antigens of IBs are different from those of WB, the abilities of IBs and WBs to distinguish the stages of recent seroconversion and open-ended chronic infection might differ. We aimed to evaluate the performance of two IBs (INNO-LIA™ HIVI/II, Fujirebio, and Geenius™ HIV1/2 Confirmatory assay, Bio-Rad) to define the stage of infection. We studied 53 patients from the French ANRS CO6 PRIMO cohort. IBs have higher positive rates than WB. However, Geenius was less sensitive than WB and INNO-LIA to detect antibodies to p31 (0% vs 22.6 % and 15.1 %, respectively), so it could wrongly label late Fiebig stage and open-ended chronic infections as recent infections (n = 5/53). For the first time, we provide evidence that centralized WBs associated with an enzyme immunoassay for the identification of recent HIV-1 infection support the establishment of a more accurate diagnosis of primary HIV infection to improve the accuracy of enrollments in cohorts of recent HIV infections useful for epidemiological studies, pathogenesis studies or therapeutic trials

Non-AIDS-Defining Events in Human Immunodeficiency Virus Controllers Versus Antiretroviral Therapy-Controlled Patients: A Cohort Collaboration from the French National Agency for Research on AIDS CO21 (CODEX) and CO06 (PRIMO) Cohorts

International audienceBackground: Low-grade chronic inflammation may persist in spontaneous human immunodeficiency virus controllers (HICs), leading to non-AIDS-defining events (nADEs). Methods: Two hundred twenty-seven antiretroviral therapy (ART)-naive HICs (known human immunodeficiency virus type 1 [HIV-1] infection ≥5 years and at least 5 consecutive viral loads [VLs] <400 HIV RNA copies/mL) were compared with 328 patients who initiated ART ≤1 month after primary HIV infection diagnosis and had undetectable VL within 12 months following ART initiation for at least 5 years. Incidence rates of first nADEs were compared between HICs and ART-Treated patients. Determinants of nADEs were assessed by using Cox regression models. Results: All-cause nADEs incidence rates were 7.8 (95% confidence interval [CI], 5.9-9.6) and 5.2 (95% CI, 3.9-6.4) per 100 person-months among HICs and ART patients, respectively (incidence rate ratio [IRR], 1.5 [95% CI, 1.1-2.2]; adjusted IRR, 1.93 [95% CI, 1.16-3.20]). After adjustment for the cohort, demographic, and immunological characteristics, the only other factor associated with all-cause nADE occurrence was age ≥43 (vs <43) years at the beginning of viral control (IRR, 1.69 [95% CI, 1.11-2.56]). The most frequent events observed in the 2 cohorts were non-AIDS-related benign infections (54.6% and 32.9% of all nADEs, respectively, for HICs and ART patients). No differences in cardiovascular or psychiatric events were observed. Conclusions: HICs experienced 2 times more nADEs than virologically suppressed patients on ART, mainly non-AIDS-related benign infections. Older age was associated with nADE occurrence, independent of immune or virologic parameters. These results do not argue in favor of expanding the ART indication for HICs but rather a case-by-case approach considering clinical outcomes such as nADEs besides immune activation

Calendar trends in sexual behaviours in a cohort of HIV-infected MSM at the era of treatment as prevention of HIV infection

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Does transient cART started during primary HIV infection undermine the long-term immunologic and virologic response on cART resumption?

International audienceWe explored the impact of transient cART started during the primary HIV-infection (PHI) on the long-term immunologic and virologic response on cART resumption, by comparison with treatment initiation during the chronic phase of HIV infection (CHI). We analyzed data on 1450 patients enrolled during PHI in the ANRS PRIMO cohort between 1996 and 2013. "Treatment resumption" was defined as at least 3 months of resumed treatment following interruption of at least 1 month of treatment initiated during PHI. "Treatment initiation during CHI" was defined as cART initiated ≥6 months after PHI. The virologic response to resumed treatment and to treatment initiated during CHI was analyzed with survival models. The CD4 cell count dynamics was modeled with piecewise linear mixed models. 136 patients who resumed cART for a median (IQR) of 32 (18-51) months were compared with 377 patients who started cART during CHI for a median of 45 (22-57) months. Most patients (97%) achieved HIV-RNA <50 cp/mL after similar times in the two groups. The CD4 cell count rose similarly in the two groups during the first 12 months. However, after 12 months, patients who started cART during CHI had a better immunological response than those who resumed cART (p = 0.01); therefore, at 36 months, the gains in √CD4 cells/mm(3) and CD4% were significantly greater in patients who started treatment during CHI. These results suggest that interruption of cART started during PHI has a significant, albeit modest negative impact on CD4 cell recovery on cART resumption