Éditorial> Des maladies infectieuses émergent ou ré-émergent de façon périodique depuis des siècles, et une partie d'entre elles est la cause d'épidémies ou de pandémies, qui peuvent décimer les populations et bouleverser les organisations sociales.Depuis les années 1970, le rythme de ces émergences de maladies à transmission vectorielle ou liées à des zoonoses s'accélère sans cesse, en lien probablement avec l'évolution démographique, l'urbanisation, l'augmentation des voyages et des échanges commerciaux, le changement d'usage des sols et la déforestation, le changement climatique.À titre d'exemple, outre le VIH (virus de l'immunodéficience humaine)/sida (syndrome d'immunodéficience acquise) responsable d'une pandémie mondiale au 20 e siècle, et les hépatites, nous avons assisté, depuis 2009, à trois épidémies majeures -dues au virus Ebola en Afrique de l'Ouest, Chikungunya et Zika en Amérique centrale et du Sud, et aux Caraïbes -et à deux pandémies, l'une due au virus de la grippe H1N1 et l'autre à un coronavirus, le severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsable de la COVID-19 (coronavirus disease 2019).Au cours de chacun de ces évènements, le constat a été le même : faiblesse dans la capacité de détection précoce, absence de moyens thérapeutiques disponibles ou prêts à entrer en phase d'essais cliniques, difficulté à développer et mettre en place des mesures préventives et des outils de prédiction, tout cela traduisant un manque d'anticipation et de préparation.Nous sommes là dans l'un des rôles majeurs qui incombe à la communauté scientifique : celui de prévenir et d'anticiper l'arrivée de nouvelles épidémies ou pandémies, pour en limiter l'impact sanitaire, économique et social.Il s'agit de se projeter au-delà de la réponse apportée à la crise lorsque celle-ci survient, en déployant une stratégie « One Health » de long terme, qui allie surveillance, compréhension et recherche scientifique, préparation, et mobilisation coordonnée du monde académique, des décideurs publics et du secteur industriel.Cette projection doit, en outre, permettre d'accroitre les capacités nationales dans ces domaines, pour renforcer la possibilité d'une réponse souveraine de la France à une future crise, en articulation forte avec l'Europe et s'inscrivant dans l'effort international de lutte contre les épidémies.Ces enjeux sont le fondement de la mission confiée à l'ANRS.Et, dans ce contexte, l'enjeu est double : préparer de manière globale la réponse à ces futures émergences ou réémergences, d'une part, comprendre et prévenir de futures émergences ou réé-
Kaposi's sarcoma (KS) was first described in 1872 [1]. In HIV patients, KS is an AIDS-defining malignancy and mainly involves the skin. KS of the bone and skeletal muscle are rare and often asymptomatic [2–4]. It has even been suggested that the presence of bone lesions assists in the differentiation of bacillary angiomatosis from AIDS-related KS, which has similar cutaneous abnormalities but not usually bone lesions [5]. Here we report the case of an HIV-infected patient with osseous KS. A 37-year-old HIV-infected homosexual man was admitted to our unit in October 2006 because of a 10 kg weight loss and extensive cutaneous KS lesions. HIV disease had been diagnosed in March 2003, when cutaneous KS lesions developed on his legs. At that time the CD4 cell count was 163 cells/μl, and the HIV viral load was 31 622 copies/ml. The patient was initiated on a combination antiretroviral therapy with efavirenz, lamivudine, and didnosine, which resulted in a partial response but did not resolve the cutaneous KS lesions, probably partly as a result of poor compliance with the treatment. In July 2006, the patient decided to stop his antiretroviral therapy. At admission in our unit, physical examination revealed an afebrile patient and the presence of new KS cutaneous lesions on his legs. Standard laboratory tests and in particular a full blood count and the C-reactive protein level were normal. The CD4 cell count was 190 cells/μl, and the HIV viral load was 16 681 copies/ml. An upper digestive fibroscopy, a colonoscopy, and chest and abdominal computed tomography (CT) scans were performed in a search for visceral KS. We found no lesions in the lungs, gastrointestinal tract, spleen, or liver. The abdominal CT scan, however, showed a para-aortic tumour and multiple osteolytic vertebral lesions with cortical disruption of the T11, T12 and L1 vertebrae, with no involvement of the overlying skin. Magnetic resonance imaging of the spine showed many more osteolytic vertebral lesions, extended from T10 to L5. These lesions emitted a hyperintense signal on short tau inversion recovery sequences and a hypointense signal on T1-weighted sequences, with an intense enhancement after contrast injection (Fig. 1). The spinal cord was normal. The tecnetium-99m-methylene diphosphonate scan showed increased uptake activity in areas corresponding to the CT scan abnormalities. The gallium-67 scan was normal. CT-guided core needle biopsy of a vertebral lesion led to an immunohistological diagnosis of KS, characterized by a massive infiltration of proliferating spindle-shaped cells, aggregates of newly formed blood vessels, and reactivity against anti-CD34, anti-CD31 and anti-human herpesvirus 8 antibodies. Retrospectively, after disclosure of the radiological findings, the patient reported mild localized back pain but only when he was questioned on the subject. The patient was treated with liposomal doxorubicin administered intravenously every 2 weeks. After 6 months of chemotherapy, the patient improved clinically, but there were no radiological changes.Fig. 1: Sagittal T1-weighted images of the patient's spine. (a) At the thoraco-lumbar junction: multiple vertebral lesions with perilesional fatty halo. (b) Fat-saturated contrast-enhanced image: marked enhancement of the lesions.KS is a multisystem and multicentric disease attributed to human herpesvirus 8 [6]. It primarly affects the skin and mucosa. Musculoskeletal KS lesions are rare, but they may also occur, mostly combined with aggressive cutaneous or mucosal KS lesions [2]. KS bone involvement develops either as a direct extension of an extensive overlying cutaneous disease or extensive lymph node lesion, or as part of a metastatic process. In a recent review of the medical literature, Caponetti and coworkers [2] identified reports concerning 66 patients with KS of the musculoskeletal system, 28 of whom had HIV infection. Bone lesions in these HIV-infected patients, as in the patient we report here, were mainly located on the axial skeleton; thus 11 of the 28 HIV-infected patients had vertebral lesions [2]. Bone KS lesions, especially of the vertebrae, may lead to spinal cord compression and neurological sequelae [7,8]. Early diagnosis of these lesions followed by systemic chemotherapy regimens and combination antiretroviral therapy are therefore essential because they may prevent the occurrence of neurological sequelae. Radiation therapy may be performed to relieve bone pain. We first suggest that patients with KS, especially those with aggressive widespread disease, should be carefully asked about bone pain. Although bone involvement in KS patients has rarely been found to be asymptomatic, bone pain is usually mild and may not be reported spontaneously [2]. In patients with bone pain a meticulous evaluation for osseous lesions should be performed using CT scans and magnetic resonance imaging. X-rays are not sensitive enough to detect osseous lesions. In addition, we would stress the fact that the presence of cutaneous abnormalities and bone lesions in HIV-infected patients should not only suggest a diagnosis of bacillary angiomatosis, but also KS with bone involvement [5]. To distinguish bacillary angiomatosis from KS, it is essential to obtain tissue for histological analysis and culture.
Abstract Background Hypermutated viruses induced by APOBEC3 (apolipoprotein B mRNA-editing, enzyme-catalytic, polypeptide-like 3) proteins comprise some of the defective viruses in the HIV reservoir. Here, we assessed the proportion of APOBEC3-induced defective proviruses in HIV-positive patients before and after receiving dolutegravir + lamivudine dual therapy. Methods PBMCs of virologically suppressed patients enrolled in the ANRS 167 LAMIDOL trial, evaluating a switch from triple therapy to dolutegravir + lamivudine, were collected 8 weeks before (W-8) and 48 weeks after (W48) dual-therapy initiation. The Vif and RT regions were subject to next-generation sequencing. Bioinformatic algorithms were developed to identify APOBEC3-defective sequences and APOBEC3-related drug resistance mutations (APOMuts). All hypermutated sequences and those containing at least one stop codon were considered as defective. Results One hundred and four patients were enrolled (median virological suppression duration: 4.2 years; IQR: 2.0–9.1). Proviral defective reads at W-8 and W48 were detected in Vif in 22% and 29% of patients, respectively, and in RT in 38% and 42% of patients, respectively. At least one APOMut was present in proviruses of 27% and 38% of patients at W-8 and W48, respectively. The ratio of APOMuts/number of potential APOMut sites was significantly higher at W48 (16.5%) than at W-8 (9.8%, P = 0.007). The presence of APOBEC3-defective viruses at W-8 was not associated with HIV total DNA level, nor with the third drug class received prior to switching to dolutegravir + lamivudine, nor with the duration of virological suppression. Conclusions Whereas no significant change in the proportion of patients with APOBEC3-defective proviruses was evidenced after 1 year of dolutegravir + lamivudine maintenance, enrichment in APOMuts was observed. Further longer-term studies are needed to assess the other forms of defective viruses with dual-therapy.
'%3e%3cpath fill='%23012169' d='M0 0v30h60V0z'/%3e%3cpath stroke='%23fff' stroke-width='6' d='m0 0 60 30m0-30L0 30'/%3e%3cpath stroke='%23C8102E' stroke-width='4' d='m0 0 60 30m0-30L0 30' clip-path='url(%23b)'/%3e%3cpath stroke='%23fff' stroke-width='10' d='M30 0v30M0 15h60'/%3e%3cpath stroke='%23C8102E' stroke-width='6' d='M30 0v30M0 15h60'/%3e%3c/g%3e%3c/svg%3e)