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.
In this sero-epidemiological study, we investigated humoral immunity to three vaccine-preventable diseases—tetanus, diphtheria and pertussis—among 331 adults (aged 18–60 years) attending vaccination centres for travellers and who had been vaccinated according to national recommendations in France. Serological results showed that the percentage of subjects with antibodies to diphtheria and tetanus decreases with age. Results also confirmed surveillance data on vaccination in France, with 7.6% of the study population (13.4% of those aged 18–29 years) having recently acquired a pertussis infection. These results confirm the importance of following French recommendations for regular boosters for tetanus and diphtheria among adults. They also indicate the need for better implementation of the current recommendations for pertussis-vaccine boosters in adults.
Abstract Background Raltegravir (RAL) has favorable tolerability and safety profile, with few and manageable drug interactions. The use of RAL 1200 mg once daily (qd) for first-line therapy is well established. We assessed efficacy and safety of RAL 1200 mg qd, as part of triple combined antiretroviral therapy (cART), for maintenance strategy. Methods The QDISS trial (NCT03195452) was a 48-week multicenter, single-arm, open-label study designed to evaluate the ability of 2 NRTIs + RAL 1200 mg qd to maintain virological suppression in HIV-1 infected subjects on a stable cART with 2 NRTIs and a third agent for at least 6 months. The primary endpoint was the proportion of participants with HIV-1 RNA < 50 copies/mL at week 24, by the FDA snapshot algorithm. Results Of 100 participants 91% maintained viral suppression (95% CI: 83.6–95.8) at week 24 and 89% (81.2–94.4) at week 48. At week 24, there was one virological failure, without emergence of resistance-associated mutation and 10 participants had discontinued, 4 because of adverse events (AEs). Over 48 weeks, 7 AEs of grade 3–4 were reported, one possibly study-drug related (spontaneous abortion). BMI remained stable regardless of previous therapy or baseline BMI category. Over 48 weeks, total cholesterol ( p = 0.023) and LDL-cholesterol ( p = 0.009) decreased, lifestyle and ease subscale significantly improved ( p = 0.04). The quality of life and Patients Reported Outcomes (PROs) also improved at W12 ( p = 0.007). Conclusion RAL 1200 mg qd as part of a maintenance triple therapy showed a high efficacy in virologically suppressed HIV-1 infected subjects, with good safety profile and improved lipid profile and patient reported outcomes. Trial registration: Clinical trials.gov NCT03195452 and EudraCT 2016-003702-13.
A 38‐year‐old woman, known to be HIV‐antibody‐positive for 2 months, presented with a progressive swelling of the right thigh of 1‐month duration. She had no history of trauma or breaking of the skin. She suffered from oral candidiasis, but had no previous AIDSdefining illness. She had no systemic symptoms such as pulmonary symptoms, weight loss, organ enlargement, or fever. Her laboratory tests were unremarkable, except for a CD4 count of 115/mm3. On examinafion, an ulcerated, fluctuating 3‐cm mass with surrounding erythema was noted with only a small volume of purrulent discharge. A punch biopsy, showing a necrotizing inflammation of the hypodermis without granulomas, and a swab and two blood cultures (Isolator 10, DuPont, Wilmington, DE, USA) were performed. The patient was discharged with a diagnosis of a bacterial abscess and treated with pristinamycin, 1 g t.i.d., and local wound care. One month later, the ulceration persisted, but the inflammation and purulent discharge had disappeared. Because direct examination of a Ziehl‐Neelsen stained specimen had revealed acid‐fast bacilli, later identified as Mycobacterium avium complex, the therapy was changed to clarithromycin, 2 g b.l.d., given for 3 months, complete healing was obtained without incision and drainage. She was given rifabutine, 300 mg once daiiy, 7 months later as her CD4 cell count became <100/mm”, No relapse had occurred after a 18‐month follow‐up.
Dolutegravir is a widespread integrase strand-transfer inhibitor (INSTI) recommended for treatment of primary HIV infection (PHI). PHI is a high-risk stage for sexual transmission because of the high viral load in semen. Yet dolutegravir concentrations in semen are lower than in blood during chronic treatment.To compare the kinetics of HIV-RNA and total HIV-DNA in the genital compartment in subjects receiving either tenofovir/emtricitabine/dolutegravir or tenofovir/emtricitabine/darunavir/cobicistat as a first-line combined ART (cART) at the time of PHI.Eighteen subjects receiving tenofovir/emtricitabine/dolutegravir and 19 receiving tenofovir/emtricitabine/darunavir/cobicistat enrolled in the ANRS169 OPTIPRIM-2 trial participated in the genital substudy.Between week (W) 0 and W2 HIV-RNA in seminal plasma (SP) decreased by 1 log10 copies/mL. Undetectable SP HIV-RNA was achieved in similar proportions between the two regimens at each timepoint. Overall, eight patients still presented detectable HIV-RNA or HIV-DNA in semen at W48; 15.4% and 28.6% presented detectable HIV-RNA and 9.1% and 14.3% presented detectable HIV-DNA in dolutegravir- and darunavir-based cART groups, respectively, with no significant difference.For the first time, to the best of our knowledge, we showed that a dolutegravir-based regimen initiated as soon as PHI reduces HIV-RNA and HIV-DNA with no difference compared with a control group receiving a darunavir-based regimen. Although the viral purge in semen seems longer after treatment in PHI than CHI, due to high viral loads, early dolutegravir-based treatment initiation permits a major decay of both viral particles and infected cells in semen, efficiently reducing the high risk of transmission during PHI.
Burkholderia pseudomallei is a gram-negative bacillus mainly distributed in South Asia, northern Australia and Iran. 1 However, its incidence is probably greatly underestimated in other regions of the tropical world due to the lack of diagnostic microbiology facilities. Multiple clinical presentations of B. pseudomallei have been reported ranging from localized,benign infection to fulminant septicemia. 2 Relapse of the infection is frequent even among those completing a full course of antibiotic treatment. Septic arthritis and osteomyelitis are an uncommon presentation of the disease; 14 cases have been reported during the last 10 years. 3,4 The optimal treatment remains elusive. We describe a case of melioidotic osteomyelitis treated with an imipenem and doxycycline regimen. A 46-year-old Englishman, who had a 3-week history of traveling in Thailand and jungle tracking at Perhentian Island, Malaysia, presented with a 10-day history of fever, chills, rigors, and right thigh pain and was admitted to Kuala Terengganu Hospital in Malaysia. On examination, he was febrile with temperature of 39.6°C. The right thigh was painful with some limitation of range of movement. A full blood count demonstrated a white cell count of 11.7 � 10 9 /L with predominant neutrophilia and an erythrocyte sedimentation rate (ESR) of 106 mm/h. Blood cultures grew B. pseudomallei and he was started with intravenous ceftazidime and amoxicillinclavulanate. Seven days later he was repatriated to France, where he used to live, and therefore was admitted to our
We investigated the decline of hepatitis B virus surface antigen (HBsAg) and core related antigen (HBcrAg) in chronic hepatitis B patients sussessfully treated with nucleos(t)ide analogues. In patients with plasma viral suppression, the baseline median levels of HBsAg and HBcrAg were 3.1 and 3.0 log U/mL, respectively. The levels in naïve patients were 4.2 and 3.6 log U/mL for HBsAg and HBcrAg, respectively. No significant decline was observed in patients with viral suppression within a year period. A low reduction was observed during the first months after treatment initiation, especially regarding HBcrAg. The dynamics of these antigens after viral suppression should be further investigated.
Abstract Chagas disease (CD) is endemic to Latin America; its prevalence is highest in Bolivia. CD is sometimes seen in the United States and Canada among migrants from Latin America, whereas it is rare in Europe. We report 9 cases of imported CD in France from 2004 to 2006.
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