The burden of secrecy in the management of multimorbidity in older people living with HIV aged 70 and over.

The secrecy surrounding HIV continues to be a major concern for older people living with HIV (OPWH) despite their long-term experience of HIV and the presence of other chronic diseases. Our study aims to highlight how the secrecy surrounding HIV can affect the management of the other conditions. The results of this socio-anthropological sub-study of the ANRS EP66 SEPTAVIH study, which assesses frailty in OPWH, are based on in-depth interviews conducted with 20 OPWH with multimorbidities aged 70 years and over and 9 caregivers. Based on a cross-sectional thematic analysis, this study shows that HIV infection differs from other chronic diseases due to the secrecy and stigma associated with HIV. These specific issues associated with HIV complicate the lives of OPWH, depriving them of support from loved ones and forcing them to exclude their general practitioner from their care system. This then causes OPWH with multiple chronic diseases to become socially vulnerable and isolated. Interventions that support the sharing of information on HIV among OPWH and also among caregivers need to be identified as a matter of urgency in order to improve the lives and management of OPWH with multimorbidities.Trial Registration: ClinicalTrials.gov identifier: NCT03958786.

Risk of HIV transmission during combined ART initiation for HIV-infected persons with severe immunosuppression.

BACKGROUND: Individuals presenting for care with severe immunosuppression typically have high plasma HIV viral load (pVL) and may transmit HIV before and after initiation of combination antiretroviral therapies (cART). PATIENTS AND METHODS: Using risk equations and data collected in the IMEA 040 DATA trial on sexual behaviour and pVL level of 84 HIV-infected patients (23 women), we estimated monthly rates of HIV transmission for each virologically unsuppressed participant (pVL >50 copies/mL) who reported sex with HIV-negative or unknown serostatus (HNUS) partners at cART initiation, 24 weeks (W24) and W48 after; rates were considered negligible for other participants. RESULTS: At cART initiation, median pVL was 5.4 log10 copies/mL. The percentage of virologically unsuppressed patients decreased, from 100% at cART initiation to 27% (95% CI 16%-43%) for heterosexuals and 8% (95% CI 2%-22%) for MSM at W48 (P < 0.001). The percentage of patients reporting sex with HNUS partners increased between cART initiation and W48, from 23% (95% CI 10%-42%) to 42% (95% CI 25%-61%) for heterosexuals (P = 0.042) and from 41% (95% CI 21%-64%) to 73% (95% CI 52%-88%) for MSM (P = 0.004). Median monthly HIV transmission rates were 0.0540 (IQR 0.0339-0.0742) for MSM and 0.0018 (IQR 0.0014-0.0191) for heterosexuals at cART initiation, and were reduced by 95% (95% CI 87%-100%) for heterosexuals and 98% (95% CI 95%-100%) for MSM as early as W24. CONCLUSIONS: Risk of onward transmission for severely immunosuppressed individuals is high before and within the first weeks of cART, and persists, at a substantially reduced level, beyond 24 weeks of cART for some individuals. Earlier cART and protecting HIV-negative partners until full viral suppression is achieved could reduce HIV transmission.

Long-term efficacy of darunavir/ritonavir monotherapy in patients with HIV-1 viral suppression: week 96 results from the MONOI ANRS 136 study.

OBJECTIVES: Long-term results at week 96 are needed to evaluate the capacity of the darunavir/ritonavir monotherapy strategy to maintain a sustained control of the HIV-1 viral load. METHODS: MONOI is a prospective, open-label, non-inferiority, randomized, 96 week trial comparing darunavir/ritonavir monotherapy versus a darunavir/ritonavir triple-therapy strategy to maintain HIV-1 viral load suppression in HIV-1-infected patients. CLINICAL TRIAL REGISTRATION: NCT00412551. RESULTS: From 225 randomized patients, 219 patients reached the 48 week follow-up and 211 reached the 96 week follow-up (106 patients in the darunavir monotherapy arm and 105 in the darunavir triple-therapy arm). Baseline characteristics were well balanced between the two treatment groups. At week 96, in intent-to-treat analysis, 91/103 patients (88%, 95% CI 81-94) allocated to the darunavir/ritonavir monotherapy arm and 87/104 patients (84%, 95% CI 75-90) allocated to the darunavir triple-therapy arm achieved an HIV-1 viral load <50 copies/mL, with no statistical difference between the two groups. Throughout the 96 week follow-up, 66/112 patients (59%, 95% CI 49-68) and 79/113 patients (70%, 95% CI 61-78) consistently had HIV-1 RNA <50 copies/mL with darunavir/ritonavir monotherapy and darunavir/ritonavir triple therapy, respectively. CONCLUSIONS: The MONOI study establishes darunavir/ritonavir monotherapy as durable and efficacious for maintaining virological suppression in HIV-1 patients. Darunavir/ritonavir monotherapy should be considered as a (tailored) treatment option for standard triple-therapy patients who have had a substantial period of viral suppression.

Body fat distribution in HIV-infected patients treated for 96 weeks with darunavir/ritonavir monotherapy versus darunavir/ritonavir plus nucleoside reverse transcriptase inhibitors: the MONOI-ANRS136 substudy.

OBJECTIVES: The aim of the study was to evaluate fat tissue distribution in HIV-infected patients with suppressed viraemia treated with darunavir/ritonavir (darunavir/r) monotherapy versus darunavir/r triple therapy. METHODS: This study was a substudy of the randomized, multicentre, open-label MONOI-ANRS 136 trial. Body fat distribution and metabolic parameters were measured at baseline, week 48 and week 96. RESULTS: In total, 156 patients of the 225 initially enrolled in the MONOI trial participated in this study, 75 in the darunavir/r monotherapy arm and 81 in the darunavir/r triple-therapy arm. The median limb fat increase from baseline was +0.34 kg [interquartile range (IQR) -0.040 to +1.140 kg; P < 0.001] at week 48 and +0.33 kg (IQR -0.14 to +1.26 kg; P = 0.001) at week 96 in the monotherapy arm, while there was no change (-0.02 kg; IQR -0.53 to +0.52 kg) at week 48 and then an increase of +0.23 kg (IQR -0.45 to +0.87 kg; P = 0.046) at week 96 in the triple-therapy arm. The two arms differed significantly at week 48 (P = 0.001) but not at week 96. The median increase in trunk fat was +0.73 kg (IQR -0.24 to +1.60 kg; P < 0.001) and 0.60 kg (IQR -0.41 to +1.49 kg; P = 0.03) at week 48 and +1.16 kg (IQR -0.17 to +2.75 kg; P < 0.001) and +0.90 kg (IQR -0.51 to +2.34 kg; P = 0.001) at week 96 in the monotherapy and triple-therapy arms, respectively, with no difference between arms. At week 96, the only biological change was a glucose level elevation in the monotherapy arm (median +4.0 mg/dL; IQR -4.0 to +7.0 mg/dL) compared with the triple-therapy arm (P = 0.012). CONCLUSIONS: Overall, body fat tissue increased in patients on darunavir/r monotherapy and triple therapy, with no difference between the arms over 96 weeks. The only difference found was a delayed increase in limb fat tissue in the triple-therapy arm compared with the monotherapy arm in the first year.

[Recurrent acute fatty liver of pregnancy: About a case and a review of the literature]. / La stéatose hépatique aiguë gravidique récidivante : à propos d'un cas et une revue de la littérature.

Acute fatty liver of pregnancy (AFLP) is a specific but rare hepatopathy that can usually complicate the third trimester of pregnancy. It is potentially fatal for the mother and the fetus. To our knowledge, only eight cases of recurrence have been published, we report a new case. The first episode presented by our 23-year-old patient was suspected in front of a cutaneous-mucosal jaundice with vomiting occurring on pregnancy of 35weeks of gestation (WG). Hyperleucytosis, abnormalities of the hepatic balance, as well as a hypoglycemia were biological elements supporting the diagnostic beam. On the other hand, medical imaging could not bring a clear confirmation. The evolution was favorable after deferred delivery by caesarean section for pulmonary maturation. Three years later, she presented to the obstetrical emergency room at 36weeks and six days of gestation, with a clinical and biological picture almost similar to that of the first episode. A caesarean section was then indicated for suspicion of recurrence. The evolution is favorable for the mother and her children. The interest of the communication on the risk of recurrence, the clinical and biological monitoring in particular in the third trimester of the subsequent pregnancy are imperative, in order to improve the prognosis of this pathology.

Randomized comparison of metabolic and renal effects of saquinavir/r or atazanavir/r plus tenofovir/emtricitabine in treatment-naïve HIV-1-infected patients.

OBJECTIVES: The aim of the study was to compare the effects on lipids, body composition and renal function of once-daily ritonavir-boosted saquinavir (SQV/r) or atazanavir (ATV/r) in combination with tenofovir/emtricitabine (TDF/FTC) over 48 weeks. METHODS: An investigator-initiated, randomized, open-label, multinational trial comparing SQV/r 2000/100 mg and ATV/r 300/100 mg once daily, both in combination with TDF/FTC, in 123 treatment-naïve HIV-1-infected adults was carried out. The primary endpoint was to demonstrate noninferiority of SQV/r compared with ATV/r with respect to the change in fasting cholesterol after 24 weeks. Secondary outcome measures were changes in metabolic abnormalities, body composition, renal function, and virological and immunological efficacy over 48 weeks. Patients who had used at least one dose of trial drug were included in the analysis. RESULTS: Data for 118 patients were analysed (57 patients on SQV/r and 61 on ATV/r). At week 24, changes in lipids were modest, without increases in triglycerides, including a significant rise in high-density lipoprotein (HDL) cholesterol and a nonsignificant decrease in the total:HDL cholesterol ratio in both arms with no significant difference between arms. Lipid changes at week 48 were similar to the changes observed up to week 24, with no significant change in the homeostasis model assessment (HOMA) index. Adipose tissue increased regardless of the regimen, particularly in the peripheral compartment and to a lesser extent in the central abdominal compartment, with an increase in adipose tissue reaching statistical significance in the ATV/r arm. A slight decline in the estimated glomerular filtration rate (eGFR) was observed in both arms during the first 24 weeks, with no progression thereafter. The immunological and virological responses were similar over the 48 weeks. CONCLUSIONS: Combined with TDF/FTC, both SQV/r 2000/100 mg and ATV/r 300/100 mg had comparable modest effects on lipids, had little effect on glucose metabolism, conserved adipose tissue, and similarly reduced eGFR. The virological efficacy was similar.

Switching the nucleoside reverse transcriptase inhibitor backbone to tenofovir disoproxil fumarate + emtricitabine promptly improves triglycerides and low-density lipoprotein cholesterol in dyslipidaemic patients.

OBJECTIVES: To assess the impact of switching to tenofovir disoproxil fumarate + emtricitabine on lipid parameters. METHODS: HIV-infected patients with plasma viral load <400 copies/mL, fasted triglycerides from 2.3 to 11.4 mmol/L and/or fasted low-density lipoprotein (LDL)-cholesterol >4.1 mmol/L were randomized to switch the nucleoside reverse transcriptase inhibitor (NRTI) backbone to fixed-dose combination tenofovir disoproxil fumarate + emtricitabine or to maintain the baseline antiretroviral regimen (the control group). The study has been registered with ClinicalTrials.gov under the identifier NCT00323492. RESULTS: Ninety-one patients were included in the intent-to-treat (ITT) analysis with triglycerides 2.4 mmol/L and LDL-cholesterol 4.0 mmol/L (median values). At week 12, the median changes from baseline of triglycerides were -0.5 mmol/L (-25%; n = 46) and -0.1 mmol/L (-6%; n = 45) in the tenofovir disoproxil fumarate + emtricitabine and control groups, respectively, indicating a difference of -0.4 mmol/L (P = 0.034) [95% confidence interval (CI): -0.9 to -0.0]. Similarly for LDL-cholesterol, changes of -0.4 mmol/L (-9%) and -0.1 mmol/L (-1%) were observed in the tenofovir disoproxil fumarate + emtricitabine and control groups, respectively, indicating a difference of -0.4 mmol/L (P = 0.031) [95% CI: -0.7 to -0.0]. The proportion of patients with LDL-cholesterol >4.1 mmol/L decreased from 48% at baseline to 26% at week 12 in the tenofovir disoproxil fumarate + emtricitabine group versus no change in the control group. No virological failure was observed during the study. CONCLUSIONS: Switching to tenofovir disoproxil fumarate + emtricitabine in dyslipidaemic HIV-infected patients improves triglycerides and LDL-cholesterol.

[Potentially malignant disorders of the oral mucosa: terminology and classification]. / Affections potentiellement malignes de la muqueuse buccale: nomenclature et classification.

The last WHO expert workgroup recommended abandoning the distinction between potentially malignant lesions and conditions. The term to use is "potentially malignant disorders". Leukoplakia is the most common of these disorders, while erythroplakia is rather rare. The diagnosis is still made by excluding other documented white or red lesions. Despite progress in molecular biology, no marker allows predicting malignant transformation. These lesions are treated surgically with or without dysplasia. It is unknown if this surgery can really prevent transformation into squamous cell carcinoma. The potential malignancy of oral lichen planus is still debated. The risk of malignant transformation is lower than that of leukoplakia. No treatment may prevent this. Other potentially malignant conditions such as oral submucous fibrosis, actinic cheilitis, lupus, and immunodeficiency are rare.

[Anti-inflammatory and repair activity of two toothpastes in an ex-vivo human gingival mucosa model]. / Comparaison de l'effet anti-inflammatoire et réparateur de deux dentifrices sur un modèle expérimental de muqueuse gingivale humaine.

INTRODUCTION: Our aim was to compare the anti-inflammatory activity of two toothpastes, one including enoxolone 1%, the other including plant extracts and sodium bicarbonate. MATERIAL AND METHODS: Gingival fragments were kept alive ex-vivo. Inflammation, inflammatory mediators (SP and LPS) were applied to culture medium on contact with corium to induce inflammation. The effect of both toothpastes was assessed with histological and biochemical parameters (inflammatory cytokine IL8) of inflammation on the synthesis of collagen and cellular viability. RESULTS: Both toothpaste "A" including enoxolone at 1% and "P" including plant extracts and sodium bicarbonate were effective on edema and vasodilatation. "A" acted on IL8 synthesis, unlike "P". Both toothpastes boosted collagen synthesis by fibroblasts. The percentage of cellular viability for "A" was superior to the currently admitted standard (80%), unlike to "P". DISCUSSION: The mechanisms of action of each toothpaste seem to be different. "A" modulates pro-inflammatory cytokine IL8 expression, unlike "P". The toothpaste "A" seems to be better tolerated.

[Anti-inflammatory effect of enoxolone in an ex-vivo human gingival mucosa model]. / Effet anti-inflammatoire de l'enoxolone dans un modèle ex-vivo de muqueuse gingivale humaine.

INTRODUCTION: Our aim was to assess the modalities of use and the anti-inflammatory activity of enoxolone included in toothpaste and in a mouthwash solution. MATERIAL AND METHODS: We used gingival fragments kept alive during 3 days at 37 degrees C. To induce inflammation, inflammatory mediators (SP and LPS) were applied to culture medium on contact with corium. The toothpaste versus placebo was applied on epithelium, in double blind. Histological analysis was then performed on hematoxylin and eosin stained slides. Edema was evaluated with semi-quantitative scores. Vasodilatation was studied by counting the percentage of dilated vessels according to scores and the surface of these dilated vessels by morphometrical image analysis. An inflammatory cytokine, IL8, was measured in culture supernatants. Dosing IL1alpha tested the mouth solution. RESULTS: The toothpaste induced a significant decrease of edema, vasodilatation, and IL8 excretion. The enoxolone solution induced a decrease of IL1alpha. DISCUSSION: Enoxolone demonstrated an anti-inflammatory property whatever the carrier was.

Metabolic disorders and chronic viral disease: the case of HIV and HCV.

The importance of metabolic disorders in the pathophysiology of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections is becoming increasingly apparent. Metabolic anomalies, with their potential for multiple-organ involvement, are to be expected, given the chronic nature of these diseases, and the intracellular dysregulation associated with them. Not only have the endocrine and cytokine metabolic anomalies seen in HIV and HCV infections been linked with the metabolic syndrome, but they also appear to have some pathways in common. Studying the differences and similarities between these metabolic anomalies may add to our understanding of HIV and HCV infection, and provide guidance on how to treat these chronic diseases. This review highlights the principal underlying factors for metabolic disorders in these chronic viral diseases-namely insulin resistance and liver damage. Both the chronic viral state itself and the host immune response give rise to glucose and lipid metabolic disorders that, in turn, are risk factors for hepatic damage. The various interactions between HIV and/or HCV with insulin resistance, type 2 diabetes, steatosis and fibrogenesis should be considered when determining the treatment and long-term follow-up of patients. Recent data indicate that HCV clearance improves insulin resistance and hepatic function in HCV-infected patients treated with interferon with or without ribavirin.

[Carcinoma of the lips]. / Carcinomes des lèvres.

Epidermoid carcinoma, that is, squamous cell carcinoma of the skin, is the most common malignant tumor of the lips. It occurs especially in men. Its primary causes are sun exposure, smoking, and chronic irritation. Leukoplakia is the most frequent precancerous lesion. Epidermoid carcinoma may appear clinically as a scaly erosion or an ulceration. Standard treatment is surgical excision with reconstruction.

[Langerhans cell histiocytosis]. / Histiocytose langerhansienne.

Langerhans cell histiocytosis (ex histiocytosis X) is usually present in children. It is a clonal proliferation of non-functional Langerhans's cells. Histological aspects are variable. The diagnosis is made in immunolabeling by anti-CD1a. Clinical presentations are variable, depending on their extension. Three syndromes are actually the same pathogenic process: eosinophilic granuloma (single or multiple osseous localizations), Hand-Schüller-Christian disease (chronic form with bone and visceral dissemination) and Abt-Letterer-Siwe disease (disseminated and acute malignant presentation).

[Nasopalatine duct cyst]. / Kyste du canal nasopalatin.

The nasopalatine cyst is the most common epithelial and non-odontogenic cyst of the maxilla. It is of embryological origin. It is different from a radicular cyst. The diagnosis is based on radiographic and histological data. The treatment is enucleation. The surgical approach depends on the size of the cyst and its anterior or posterior extension. Excision must be total to avoid relapse which may occur beyond 5 years. Long-term follow-up is essential.

[Jaw muscle tumors]. / Tumeurs musculaires des mâchoires.

Muscular tumors are rare. They hardly ever present in jaws. Rhabdomyoma have never been reported in this localization. Clinical and radiological features are non-specific. The diagnosis is based on histopathological features. It is difficult to make for leiomyosarcoma. Surgical excision is the recommended treatment, conservative for leiomyoma, radical for other malignant tumors. Rhabdomyosarcoma has a good prognosis unlike leiomyosarcoma.

[Nasolabial cyst]. / Kyste nasolabial.

Nasolabial cyst is a rare epithelial and non-odontogenic cyst of the jaw. It is situated behind the ala nasi, extending backwards into the inferior nasal meatus and forward into the labio-gingival sulcus. Predominant symptoms are swelling of the nasal vestibule, local pain, and nasal obstruction. Radiology is not specific and CT scan may be contributive. Surgical excision is the first line treatment; it proves the diagnosis and prevents recurrence.

[Desmoplastic fibroma]. / Fibrome desmoïde.

Desmoplastic fibroma is a rare benign intraosseous neoplasms. They can affect the jaw. Posterior mandibular bone involvement is the most frequent localization. They are locally aggressive and recurrence is frequent. Radioclinical signs are not specific and the histological diagnosis may be difficult. Extended surgical removal is the recommended treatment.

Viral efficacy maintained and safety parameters improved with a reduced dose of stavudine: a pilot study.

OBJECTIVES: Stavudine (d4T) is a potent but potentially toxic nucleoside reverse transcriptase inhibitor that is still widely used in developing countries. This study's aim was to determine the efficacy and safety profile of lower-dose d4T. METHODS: Multi-centre, open-label, single-arm, pilot, 48-week study in French patients weighing >60 kg with viral load <400 HIV-1 RNA copies/mL who were receiving d4T 40 mg twice daily and then switched to 30 mg twice daily. The primary endpoint was the proportion with plasma viral load <400 copies/mL at week 24. Secondary endpoints included the proportion with <50 copies/mL at weeks 24 and 48, changes in mitochondrial DNA, CD4 cell count and pharmacokinetics, and clinical and laboratory safety. RESULTS: Fifty-seven patients enrolled. Baseline CD4 count was 584 cells/microL; viral loads were <400 copies/mL and <50 copies/mL in 100% and 89%, respectively. Prior antiretroviral drug exposure was 6.9 years, d4T exposure was 6.3 years. Fifty-six out of 57 (98%) patients had viral load <400 copies/mL and 51 (89%) had viral load <50 copies/mL at week 24. Median CD4 count increased by 63 cells/microL at week 48 (P=0.006). At 48 weeks, total cholesterol decreased by 0.24 mmol (P=0.02), high-density lipoprotein cholesterol by 0.15 mmol (P=0.0001) and alanine aminotransferase by 5.74 mg/dL (P=0.01). Paired baseline DNA and week 24 RNA mutations were unchanged. Mitochondrial DNA (copies/cell) content increased from 672+/-254 to 682+/-269. d4T area under the plasma concentration time curve (AUC) decreased by 31% (P=0.003) and C(max) by 44% (P=0.004). Clinical and laboratory parameters improved or were unchanged. CONCLUSIONS: Reduced-dose d4T is effective with improved safety parameters.