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Interleukin 32 (IL-32) is a potent multi-isoform proinflammatory cytokine, which is upregulated in people with HIV (PWH) and is associated with cardiovascular disease (CVD) risk. However, the impact of IL-32 isoforms on CD4 T-cell cardiotropism, a mechanism potentially contributing to heart inflammation, remains unknown. Here we show that IL-32 isoforms β and γ induce the generation of CCR4+CXCR3+ double positive (DP) memory CD4 T-cell subpopulation expressing the tyrosine kinase receptor c-Met, a phenotype associated with heart-homing of T cells. Our ex vivo studies on PWH show that the frequency of DP CD4 T cells is significantly higher in individuals with, compared to individuals without, subclinical atherosclerosis and that DP cells from antiretroviral-naive and treated individuals are highly enriched with HIV DNA. Together, these data demonstrate that IL-32 isoforms have the potential to induce heart-homing of HIV-infected CD4 T cells, which may further aggravate heart inflammation and CVD in PWH. [ABSTRACT FROM AUTHOR]

Background Chronic inflammation persists in some people living with human immunodeficiency virus (HIV) during antiretroviral therapy and is associated with premature aging. The glycoprotein 120 (gp120) subunit of HIV-1 envelope sheds and can be detected in plasma, showing immunomodulatory properties even in the absence of detectable viremia. We evaluated whether plasma soluble gp120 (sgp120) and a family of gp120-specific anti–cluster A antibodies, linked to CD4 depletion in vitro, contribute to chronic inflammation, immune dysfunction, and subclinical cardiovascular disease in participants of the Canadian HIV and Aging Cohort Study with undetectable viremia. Methods Cross-sectional assessment of sgp120 and anti–cluster A antibodies was performed in 386 individuals from the cohort. Their association with proinflammatory cytokines and subclinical coronary artery disease was assessed using linear regression models. Results High levels of sgp120 and anti–cluster A antibodies were inversely correlated with CD4+ T cell count and CD4/CD8 ratio. The presence of sgp120 was associated with increased levels of interleukin 6. In participants with detectable atherosclerotic plaque and detectable sgp120, anti–cluster A antibodies and their combination with sgp120 levels correlated positively with the total volume of atherosclerotic plaques. Conclusions This study showed that sgp120 may act as a pan toxin causing immune dysfunction and sustained inflammation in a subset of people living with HIV, contributing to the development of premature comorbid conditions. [ABSTRACT FROM AUTHOR]

Poliovirus, the etiologic agent of paralytic poliomyelitis, can cause acute flaccid paralysis (AFP) (1). Three serotypes of poliovirus (1, 2, and 3) belong to Enterovirus species C (family Picornaviridae, genus [...]

Le but de notre étude était d'évaluer les résultats du traitement chirurgicale du plastron appendiculaire après appendicectomie différée ou immédiate. Il s'agit d'une étude rétrospective de type descriptif allant de Janvier 2000 au 31 Décembre 2007 portant sur 27 patients reçus et traités pour plastron appendiculaire. Le diagnostic était clinique par la présence d'une masse à la fosse iliaque droite, échographique, ou per opératoire. Tous les patients opérés en urgence ont été classés dans le groupe I et ceux opérés à froid, groupe II. Nous avons noté 18 hommes et 9 femmes avec un sex-ratio homme /femme = 3. L'âge moyen de nos patients était de 33 ans avec des extrêmes de 19 et 57 ans. Les signes cliniques étaient dominés par la douleur à la fosse iliaque droite et la fièvre respectivement 25 (92,6%) et 15 (55,6%) des cas. Dans le groupe I, l'appendicectomie n'a pu être réalisée pour 7 patients (n = 15) dû aux difficultés opératoires. Dans les autres cas, l'appendicectomie était possible au prix de l'élargissement de l'incision de Mac Burney et une durée de séjour plus longue. Le groupe II a concerné 12 patients (n = 12) avec 9 abords laparoscopiques et dans 3 cas, la voie de Mac Burney a été empruntée. Trois cas d'adhérences péritonéales ont été notés lors de la coelioscopie. L'appendicectomie à froid du plastron appendiculaire est un procédé sûr et efficace. Elle permet d'éviter les cicatrices inesthétiques et les fistules digestives iatrogènes. L'appendicectomie immédiate doit être abandonnée chez les patients porteurs de plastron appendiculaire car elle engendre beaucoup de morbidité.

Objective To evaluate whether single-dose treatments are as effective as standard therapy in the syndromic management of vaginal discharge. Methods A randomized controlled effectiveness trial compared single-dose tinidazole plus fluconazole (TF) with treatment for 7 days with metronidazole plus 3 days of treatment with vaginal clotrimazole (MC) among 1570 women presenting with vaginal discharge at primary health care institutions in Ghana, Guinea, Mali and Togo. Participants were randomly allocated to one of the two treatments by research nurses or physicians using precoded envelopes. Effectiveness was assessed by symptomatic response on day 14. Clinical identifier ClinicalTrials.gov NCT00313131. Findings The two treatment regimens had similar effectiveness: complete resolution was seen in 66% (TF) and 64% (MC) and partial resolution in 33% (TF) and 34% (MC) of participants (P = 0.26). Effectiveness was similar among subgroups with vulvovaginal candidiasis, Trichomonas vaginalis vaginitis or bacterial vaginosis. The two treatment regimens had a similar effectiveness among human immunodeficiency virus (HIV)-infected (TF: n = 76, 71% complete resolution, 28% partial; MC: n = 83, 72% complete resolution, 25% partial, P = 0.76) and HIV-uninfected women (TF: n = 517, 68% complete, 32% partial; MC: n = 466, 65% complete, 33% partial, P = 0.20). Cervical infections with Neisseria gonorrhoeae, Chlamydia trachomatis and Mycoplasma genitalium were uncommon among women not involved in sex work, were associated with bacterial vaginosis or T. vaginalis vaginitis, and did not alter response to treatment with agents active against vaginal infections. Four-fifths of women not relieved by a single dose of TF had a favourable response when MC was administered as second-line treatment. Conclusion Single-dose TF is as effective as multiple-dose MC in the syndromic management of vaginal discharge, even among women with HIV-infection. Given its low price and easier adherence, TF should be considered as a first-line treatment for vaginal discharge syndrome. Objectif Evaluer l'efficacite comparative des traitements par dose unique et du traitement standard pour la prise en charge syndromique de la leucorrhee. Methodes Un essai controle randomise a compare l'efficacite d'une dose unique de l'association tinidazole/fluconazole (TF) a celle d'un traitement de sept jours par le metronidazole, complete par trois jours sous clotrimazole vaginal (MC), chez 1570 femmes presentant une leucorrhee accueillies par des centres de soins de sante primaires au Ghana, en Guinee, au Mail et au Togo. Les participantes ont ete reparties de maniere aleatoire au moyen d'enveloppes precodees en deux groupes de traitement par les infirmieres ou les medecins charges de mener l'etude. L'efficacite therapeutique a ete evaluee d'apres la reponse symptomatique au quatorzieme jour. Identificateur clinique ClinicalTrials.gov NCT00313131. Resultats On a constate une efficacite similaire pour les deux traitements : on a observe une resolution complete chez 66 % des participantes traitees par TF et chez 64 % de celles traitees par MC ainsi qu'une resolution partielle chez 33 % des femmes traitees parTF et 34 % des femmes traitees par MC (p = 0,26). Une efficacite analogue a egalement ete constatee chez les sousgroupes presentant une candidose vulvovaginale, une vaginite a Trichomonas vaginalis ou une vaginose bacterienne. L'efficacite des deux traitements etait similaire chez les femmes infectees par le virus de l'immunodeficience humaine (VlH) (TF: n = 76, resolution complete 71%, resolution partielle 28 % ; MC: n = 83, resolution complete 72 %, resolution partielle 25 %, p = 0,76) et chez les femmes non infectees par le VlH (TF: n = 517, resolution complete 68 %, resolution partielle 32 % ; MC: n = 466, resolution complete 65 %, resolution partielle 33 %, p = 0,20). Les infections du col par Neisseria gonorrhoeae, Chlamydia trachomatis et Mycoplasma genitalium etaient peu frequentes chez les femmes ne pratiquant pas le commerce du sexe, etaient associees a une vaginose bacterienne ou a une vaginite a T. vaginalis et ne modifiaient pas la reponse au traitement par des agents actifs contre les infections vaginales. Chez les quatre-cinquiemes des femmes qui n'avaient pas ete soulagees par une dose unique de TF, on a observe une reponse favorable lors de l'administration de MC comme traitement de deuxieme intention. Conclusion L'association TF sous forme de dose unique est aussi efficace que l'association MC administree en plusieurs doses dans la prise en charge syndromique de la leucorrhee, meme chez les femmes infectees par le VlH. Compte tenu de son cout peu eleve et de l'observance plus facile, il faudrait envisager de classer l'association TF parmi les traitements de premiere intention de la leucorrhee. Objetivo Determinar si los tratamientos de dosis unica son eficaces como terapia estandar en el manejo sindromico del flujo vaginal. Metodos En un ensayo controlado aleatorizado se comparo la eficacia de una dosis unica de tinidazol y fluconazol (TF) con la de un tratamiento con metronidazol durante 7 dias seguido de clotrimazol vaginal durante 3 dias mas (MC) en un total de 1570 mujeres que acudieron con problemas de flujo vaginal a establecimientos de atencion primaria de Ghana, Guinea, Mali y Togo. Utilizando sobres precodificados, enfermeras y medicos investigadores asignaron aleatoriamente a las participantes a alguno de los dos tratamientos. La eficacia se evaluo determinando la respuesta sintomoetica a los 14 dias. Identificador clinico ClinicalTrials.gov NCT00313131. Resultados Los dos regimenes terapeuticos tuvieron una eficacia parecida: curacion completa en el 66% (TF) y el 64% (MC) de los casos, y curacion parcial en el 33% (TF) y el 340 (MC) de los casos (P = 0,26). La eficacia fue similar entre los subgrupos con candidiasis vulvovaginal, vaginitis pot Trichomonas vaginalis o vaginosis bacteriana. Los dos regimenes terapeuticos tuvieron tambien parecida eficacia en las pacientes infectadas por el virus de la inmunodeficiencia humana (VlH) (TF: n = 76, curacion completa en el 71% de los casos, y parcial en el 28% de los casos; MC: n = 83, curacion completa en el 72% de los casos, y parcial en el 25%; P= 0,76) y las no infectadas pot el VIH (TF: n = 517, curacion completa en el 68% de los casos, y parcial en el 32%; MC: n = 466, curacion completa en el 65% de los casos, y parcial en el 33%; P = 0,20). Las infecciones cervicouterinas por Neisseria gonorrhoeae, Chlamydia trachomatis y Mycoplasma genitalium eran infrecuentes entre las mujeres que no eran profesionales del sexo, se asociaban a vaginosis bacteriana o vaginitis por T. vaginalis, y no influian en la respuesta al tratamiento con productos activos contra las infecciones vaginales. Las cuatro quintas partes de las mujeres que no respondian a una dosis unica de TF presentaron una respuesta favorable al uso de MC como tratamiento de segunda linea. Conclusion La dosis unica de TF es tan eficaz como las dosis multiples de MC en el manejo sindromico del flujo vaginal, incluso entre las mujeres con infeccion por VlH. Teniendo en cuenta su bajo precio y el mayor cumplimiento del regimen, la combinacion TF deberia ser siempre una alternativa a considerar como tratamiento de primera linea del sindrome de flujo vaginal., Introduction Despite the contradictory results of large trials in East Africa, the syndromic management of sexually transmitted infections (STI) remains a public health priority: whether or not it reduces transmission [...]

A study was conducted to determine whether the prostate-specific antigen (PSA) could be used as a biological marker of unprotected intercourse. The results showed that PSA could be measured as a marker of unprotected intercourse during surveys aiming to measure the prevalence of HIV and other sexually transmitted infections or those primarily interested in sexual behavior, as long as participants agree to provide a self-inserted vaginal swab.

Persistent immune activation and inflammation in people living with HIV (PLWH) are associated with immunosenescence, premature aging and increased risk of non-AIDS comorbidities, with the underlying mechanisms not fully understood. In this study, we show that downregulation of the T-cell immunoglobulin receptor CD96 on CD8+ T cells from PLWH is associated with decreased expression of the co-stimulatory receptors CD27 and CD28, higher expression of the senescence marker CD57 and accumulation of a terminally differentiated T-cell memory phenotype. In addition, we show that CD96-low CD8+ T-cells display lower proliferative potential compared to their CD96-high counterparts and that loss of CD96 expression by HIV-specific CD8+ T-cells is associated with a suboptimal response to HIV antigens. In conclusion, our results suggest that CD96 marks CD8+ T-cells with competent responses to HIV and the loss of its expression might be used as a biomarker for CD8+ T-cell senescence and dysfunction in PLWH. [ABSTRACT FROM AUTHOR]

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Elite controllers (ECs) are a rare subset of HIV-1 slow progressors characterized by prolonged viremia suppression. HLA alleles B27 and B57 promote the cytotoxic T lymphocyte (CTL)-mediated depletion of infected cells in ECs, leading to the emergence of escape mutations in the viral capsid (CA). Whether those mutations modulate CA detection by innate sensors and effectors is poorly known. Here, we investigated the targeting of CA from B27/B57+ individuals by cytosolic antiviral factors Mx2 and TRIM5α. Toward that aim, we constructed chimeric HIV-1 vectors using CA isolated from B27/B57+ or control subjects. HIV-1 vectors containing B27/B57+-specific CA had increased sensitivity to TRIM5α but not to Mx2. Following exposure to those vectors, cells showed increased resistance against both TRIM5α-sensitive and -insensitive HIV-1 strains. Induction of the antiviral state did not require productive infection by the TRIM5α-sensitive virus, as shown using chemically inactivated virions. Depletion experiments revealed that TAK1 and Ubc13 were essential to the TRIM5α-dependent antiviral state. Accordingly, induction of the antiviral state was accompanied by the activation of NF-κB and AP-1 in THP-1 cells. Secretion of IFN-I was involved in the antiviral state in THP-1 cells, as shown using a receptor blocking antibody. This work identifies innate activation pathways that are likely to play a role in the natural resistance to HIV-1 progression in ECs. [ABSTRACT FROM AUTHOR]