[HIV-associated haematological complications]. / Pathologies hématologiques liées à l'infection par le VIH.

Despite recent advances in combined anti- retroviral therapy that have profoundly changed the prognosis of HIV infection, HIV-associated haematological complications remains frequent whatever the stage of the disease. Some types of lymphoma observed a dramatic reduction in their incidences but others such as diffuse B-cell lymphoma and Hodkin lymphoma remain as frequent as before the CART era. Treatments for lymphoma are nowadays not different for people living with HIV than for others. Other non- neoplastic diseases such as immune thrombo- penic purpura, thrombotic microangiopathies and hemophagocytic lymphohistiocytosis are still associated with HIV infection and will be discussed.

Bien que les traitements antirétroviraux combinés aient profondément modifié le pronostic de l'infection par le VIH, les complications hématolo- giques associées au VIH restent fréquentes à tous les stades de la maladie. Certains types de lymphomes ont vu leur incidence fortement diminuer alors que d'autres (lymphome B diffus et lymphome de Hodgkin) ont gardé une incidence stable. Le traitement de ces lymphomes n'est plus censé différer entre les personnes vivant avec le VIH et les autres. Les pathologies non malignes telles que les purpuras thrombo- péniques immuns, les microangiopathies thrombotiques et les syndromes d'activation macrophagiques, également associées au VIH, seront également abordées.

Late presentation to HIV testing is overestimated when based on the consensus definition.

OBJECTIVES: In 2011, a consensus was reached defining "late presenters" (LPs) as individuals presenting for care with a CD4 count < 350 cells/µL or with an AIDS-defining event, regardless of CD4 count. However, a transient low CD4 count is not uncommon in recent infections. The objective of this study was to investigate how measurements of late presentation change if the clinical stage at the time of diagnosis is taken into account. METHODS: Case surveillance data for newly diagnosed patients in Belgium in 1998-2012 were analysed, including CD4 count at diagnosis, the presence of AIDS-defining events, and recent infections (< 6 months) as reported by clinicians in the case of acute illness or a recent negative test. First, proportions of LPs were calculated according to the consensus definition. Secondly, LPs were reclassified as "nonlate" if infections were reported as recent. RESULTS: A total of 7949 HIV diagnoses were included in the study. Recent infections were increasingly reported over time, accounting for 8.2% of new infections in 1998 and 37.5% in 2012. The consideration of clinical stage significantly modified the proportion of LPs: 18.2% of men who have sex with men (MSM) diagnosed in 2012 would be classified as LPs instead of 30.9% using the consensus definition (P < 0.001). The proportion of patients misclassified as LPs increased significantly over time: 5% in MSM in 1998 vs. 41% in 2012. CONCLUSIONS: This study suggests that low CD4 counts in recent infections may lead to overestimation of late presentation when applying the consensus definition. The impact of transient CD4 count on late presentation estimates should be assessed and, if relevant, the introduction of clinical stage in the definition of late presentation should be considered.

Implementation of latent tuberculosis screening in HIV care centres: evaluation in a low tuberculosis incidence setting.

The screening and treatment of latent tuberculosis infection (LTBI) to prevent active tuberculosis (TB) is recommended by the WHO in all HIV-infected patients. The aim of this study was to evaluate its implementation within Belgium's HIV care. A multiple-choice questionnaire was sent to 55 physicians working in the country's AIDS reference centres. Response rate reached 62%. Only 20% screened all their HIV-infected patients for LTBI. Screening methods used and their interpretation vary from one physician to another. The main barriers to the implementation of LTBI screening and treatment, as perceived by the participants, are lack of sensitivity of screening tools, risks associated with polypharmacy and toxicity of treatment. The poor coverage of LTBI screening reported here and the inconsistency in methods used raises concern. However, this was not unexpected as, in low-TB incidence countries, who, when and how to screen for LTBI remains unclear and published guidelines show important disparities. Recently, a targeted approach in which only HIV-infected patients at highest risk of TB are screened has been suggested. Such a strategy would limit unnecessary exposure to LTBI treatment. This methodology was approved by 80% of the participants and could therefore achieve greater coverage. Its clinical validation is still pending.

[HIV infection : Reaching a zero risk of transmission]. / Transmission du VIH : Est-ce une fatalité ?

Despite a global reduction in the prevalence of HIV-infection, the HIV-epidemic is far from over. The prevention of HIV-transmission in all its forms (sexual, mother-to-child etc) must therefore remain a pillar in the fight against AIDS, and both potent and accessible prevention strategies are required. In addition to the classical and wellknown methods such as the condom, ant iretroviral therapy represents a potent prevention tool and the residual risk of transmission of correctly treated HIV-positive persons is virtually nihil. Antiretroviral therapy may and should be used in the prevention of HIV-transmission as Treatment as Prevention (TasP), Pre-Exposure Prophylaxis (PrEP), and Post- Exposure Prophylaxis (PEP). However, because of their exorbitant costs, the accessibility of these prevention strategies is limited, particularly for the most vulnerable populations.

Si l'infection par le VIH est globalement en diminution dans le monde, nous n'apercevons pas encore la fin de l'épidémie. Dès lors, nous avons besoin de moyens performants et accessibles pour tous pour diminuer la transmission du virus, essentiellement sexuelle mais aussi via la transmission de la mère à son enfant. En plus des moyens utilisés de façon répandue tel que le préservatif, le traitement antirétroviral représente à ce jour un outil très performant en termes de prévention, à travers la prophylaxie pré-exposition, la prophylaxie postexposition et le traitement de la personne infectée qui voit son risque de transmission virtuellement annulé. Néanmoins, l'accès à ces molécules coûteuses reste difficile pour les populations les plus défavorisées.

Good continuum of HIV care in Belgium despite weaknesses in retention and linkage to care among migrants.

BACKGROUND: The Belgian HIV epidemic is largely concentrated among men who have sex with men and Sub-Saharan Africans. We studied the continuum of HIV care of those diagnosed with HIV living in Belgium and its associated factors. METHODS: Data on new HIV diagnoses 2007-2010 and HIV-infected patients in care in 2010-2011 were analysed. Proportions were estimated for each sequential stage of the continuum of HIV care and factors associated with attrition at each stage were studied. RESULTS: Of all HIV diagnosed patients living in Belgium in 2011, an estimated 98.2% were linked to HIV care, 90.8% were retained in care, 83.3% received antiretroviral therapy and 69.5% had an undetectable viral load (<50 copies/ml). After adjustment for sex, age at diagnosis, nationality and mode of transmission, we found lower entry into care in non-Belgians and after preoperative HIV diagnoses; lower retention in non-Belgians and injecting drug users; higher retention in men who have sex with men and among those on ART. Younger patients had lower antiretroviral therapy uptake and less viral suppression; those with longer time from diagnosis had higher ART uptake and more viral suppression; Sub-Saharan Africans on ART had slightly less viral suppression. CONCLUSIONS: The continuum of HIV care in Belgium presents low attrition rates over all stages. The undiagnosed HIV-infected population, although not precisely estimated, but probably close to 20% based on available survey and surveillance results, could be the weakest stage of the continuum of HIV care. Its identification is a priority along with improving the HIV care continuum of migrants.

[Which immunizations for which adults in 2011?]. / Quelles vaccinations pour quels adultes en 2011?

Immunizations are extremely efficient in prevention of diseases with a lethal potential. Healthy adults, pregnant women and patients suffering from chronic diseases may have a different benefit from vaccine available in our country. Numerous health problems need to be addressed during a short consultation, relegating immunization to a position of secondary importance. This paper will address the issue of immunization in special circumstances such as: healthy adults, pregnant women, HIV-infected patients, patients with end-stage renal disease, patients with chronic liver diseases and solid organ transplant candidates and recipients.

A woman with recurrent "infections" since birth--a new mevalonate kinase mutation.

A tired 32-year-old woman complaining of tiredness was referred for work-up of a possible immune deficiency. She had a history of recurrent infections since birth, which usually responded to antibiotics within a few days. Her mother, a nurse, had reported that early charts had disappeared. Munchausen's by proxy was suspected for years. Careful anamnesis indicated possible recurrent fever. Serum IgD levels were high, which led us to suspect Hyper IgD Syndrome. Sequencing of the mevalonate kinase gene revealed 2 mutations, leading to amino acid substitutions: one already described (V3771) and R40W: never reported before. Mevalonate kinase activity was very low in the patient's peripheral blood cells. We used the "Poly Phen" prediction program successfully. Our experiments confirmed the diagnosis of mevalonate kinase deficiency. We used steroids to abort recurrent crises.

Preimplantation genetic diagnosis in an HIV-serodiscordant couple carrier for sickle cell disease: lessons from a case report.

Since 1999, the Erasme Hospital Fertility Clinic has carried a special programme for patients with HIV seropositivity. The philosophy of the programme is to give access to these patients in a secure environment to the same technological facilities available to any other patients. Many of these patients being native from sub-Saharan countries, they are often sickle cell disease (SCD) carriers, a common autosomal recessive disorder in these regions, and a severe affection in homozygotes. We hereby report, for the first time, the birth of a healthy sickle haemoglobin (HbS) heterozygous baby after preimplantation genetic diagnosis (PGD) for SCD in an HIV-serodiscordant couple of HbS mutation carriers with longstanding infertility. The prospective mother was 35 years old and HIV positive with an undetectable viral load under highly active antiretroviral therapy. One carrier embryo was transferred and resulted in the birth of a healthy HbS carrier baby girl. Despite stimulation difficulties, sometimes described in HIV patients, PGD represents an interesting additional technology, especially in populations where the coexistence of both diseases is frequent. PGD could even be preferred to prenatal diagnosis for couples of HbS carriers if the woman is HIV positive, as invasive prenatal samplings carry a risk of materno-foetal viral transmission.

Identification and characterization of mRNAs differentially expressed in thyroid cells stimulated by a mitogenic treatment.

The aim of our work is to identify new genes and proteins involved in the control of the proliferation of thyroid cells as putative protooncogenes and antioncogenes. Several strategies are discussed. A first study has allowed to identify three new genes. Further search will use the differential display and gene arrays methodology. The role of the identified proteins coded by the genes is studied in vitro by the search of partner proteins by the double hybrid method and in vivo by mice gene knockout technology.

Histological analysis of limb defects induced in developing limb buds of NMRI mouse embryos after oral administration of 3-3-dimethyl-1-phenyltriazene (DMPT) to their mother on day 10 of gestation.

A single oral dose of DMPT was given to pregnant NMRI mice on day 10 of gestation and the subsequent histological changes were studied in serial sections of affected limb buds isolated from 13-, 12- and 11-day treated embryos. Differences in abnormal skeletal patterns observed between fore- and hindlimb buds as well as between embryos from different litters provided clear evidence that the teratogen hits preferentially undifferentiated preskeletal mesoderm just before blastema formation. Absence or severe reduction of skeletal rudiments characterizes selectively the girdle and stylopod of hindlimbs and the zeugopod and autopod in forelimbs. In embryos slightly more advanced at the time of drug administration, the defects shifted in the zeugopod and distal segment of the posterior limb and in the distal segment only of the anterior limbs. In all cases, defects in the two distal segments displayed a postaxial predominance. Extensive cell death detected in the undifferentiated mesoderm of the affected limb parts of 11-day embryos similarly exhibited a postaxial predominance with the maximal damage in the ZPA territory. Together with the regular genesis of a postaxial subectodermal bleb in that area, followed by local involution of the AER, this observation strongly suggests that the teratogenic injury might involve an early impairment of ZPA and AER properties. In addition, predictive signs of hyperphalangy of digit I and distal duplication of the IId to e could be correlated with a transient reactional hyperplasia restricted to the preaxial part of the AER.

Ear malformations in the mouse embryo following maternal administration of triazene, with clinical implications.

Triazene administration to 10-day pregnant mice gave rise to severe ear abnormalities, including middle ear ossicle malformations. The head of the malleus and the body of the incus were sometimes absent. In some instances, the stapes appeared dysplastic. The stapedial artery was often quite dilated, as well as other cephalic vessels, but qualitatively normal. Severe inner ear abnormalities were observed, as well as auditory nerve disruption, which was associated with central nervous system lesions. Multiple haematomas were present in the embryonic face, but ear abnormalities occurred even in the absence of local hemorrhages. We postulate a direct effect of the teratogen on the branchial mesenchyme. This model seems to be useful for the comprehension of human middle ear abnormalities, but does not constitute a phenocopy of hemicranial microscomia.