As people living with HIV (PLHIV) age, the burden of non-HIV related comorbidities increases resulting in additional healthcare costs. The present study aimed to describe the profile, the prevalence ...and the incremental costs of non-HIV related comorbidities in PLHIV compared to non-HIV matched controls (1:2 ratio) in France.
The French permanent sample of health beneficiaries (Echantillon généraliste de bénéficiaires EGB), a claims database representative of the national population, was used to assess comorbidities in PLHIV which were identified by the ICD-10 diagnosis codes of hospitalization, full healthcare coverage, and drug reimbursements between 2011 and 2014. The control group was matched by year of birth, gender, region of residence, and economic status. Total costs of outpatient care and hospitalizations were analysed from a societal perspective. A general linear model was used to assess the incremental cost per patient in PLHIV.
A total of 1,091 PLHIV and 2,181 matched controls were identified with a mean ± standard deviation age of 46.7 ± 11.5 years. The prevalence of alcohol abuse (5.8% vs 3.1%; p<0.001), chronic renal disease (1.2% vs 0.3%; p = 0.003), cardiovascular disease (7.4% vs 5.1%; p = 0.009), dyslipidaemia (22% vs 15.9%; p<0.001), hepatitis B (3.8% vs 0.1%; p<0.001) and hepatitis C (12.5% vs 0.6%; p<0.001) was significantly higher in PLHIV compared with non-HIV controls. Other comorbidities such as anaemia, malnutrition, psychiatric diseases, and neoplasms were also more prevalent in PLHIV. Hospitalizations were significantly increased in PLHIV compared to controls (33.2% vs 16%; p<0.001). Mean total cost was 6 times higher for PLHIV compared to controls and 4 times higher after excluding antiretroviral drugs (9,952€ vs. 2,593€; p<0.001). Higher costs per person in PLHIV were significantly associated to aging (42€ per patient/year), chronic cardiovascular disease (3,003€), hepatitis C (6,705€), metastatic carcinoma (6,880€) and moderate or severe liver disease (6,299€).
Our results demonstrated an increase in non-HIV related comorbidities among PLHIV compared to matched controls. This study contributes to raise awareness on the burden of chronic comorbidities.
Patients with autoimmune and/or inflammatory diseases (AIIDs) are prone to serious infectious complications such as Pneumocystis jirovecii pneumonia (PJP). In non-HIV patients, the prognosis is ...poorer, and diagnostic tests are of lower sensitivity. Given the low incidence of PJP in AIIDs, with the exception of granulomatosis with polyangiitis, and the non-negligible side effects of chemoprophylaxis, routine prescription of primary prophylaxis is still debated. Absolute peripheral lymphopenia, high doses of corticosteroids, combination with other immunosuppressive agents, and concomitant lung disease are strong predictors for the development of PJP and thus should warrant primary prophylaxis. Trimethoprim-sulfamethoxazole is considered first-line therapy and is the most extensively used drug for PJP prophylaxis. Nevertheless, it may expose patients to side effects. Effective alternative drugs such as atovaquone or aerosolized pentamidine could be used when trimethoprim-sulfamethoxazole is not tolerated or contraindicated. No standard guidelines are available to guide PJP prophylaxis in patients with AIIDs. This review covers the epidemiology, risk factors, and prevention of pneumocystis in the context of AIIDs.
Human monkeypox virus is spreading in Europe and the USA among individuals who have not travelled to endemic areas.1 On July 23, 2022, monkeypox was declared a Public Health Emergency of ...International Concern by WHO Director-General Tedros Adhanom Ghebreyesus.2 Human-to-human transmission of monkeypox virus usually occurs through close contact with the lesions, body fluids, and respiratory droplets of infected people or animals.3 The possibility of sexual transmission is being investigated, as the current outbreak appears to be concentrated in men who have sex with men and has been associated with unexpected anal and genital lesions.1,4 Whether domesticated cats and dogs could be a vector for monkeypox virus is unknown. Both samples contained virus of the hMPXV-1 clade, lineage B.1, which has been spreading in non-endemic countries since April, 2022, and, as of Aug 4, 2022, has infected more than 1700 people in France, mostly concentrated in Paris, where the dog first developed symptoms. ...the virus that infected patient 1 and the virus that infected the dog showed 100% sequence homology on the 19·5 kilobase pairs sequenced. Given the dog's skin and mucosal lesions as well as the positive monkeypox virus PCR results from anal and oral swabs, we hypothesise a real canine disease, not a simple carriage of the virus by close contact with humans or airborne transmission (or both).
Anecdotal evidence rapidly accumulated during March 2020 from sites around the world that sudden hyposmia and hypogeusia are significant symptoms associated with the SARS-CoV-2 pandemic. Our ...objective was to describe the prevalence of hyposmia and hypogeusia and compare it in hospitalized and non-hospitalized COVID-19 patients to evaluate an association of these symptoms with disease severity. We performed a cross-sectional survey during 5 consecutive days in March 2020, within a tertiary referral center, associated outpatient clinic, and two primary care outpatient facilities in Paris. All SARS-CoV-2-positive patients hospitalized during the study period and able to be interviewed (
n
= 198), hospital outpatients seen during the previous month (
n
= 129), and all COVID-19-highly suspect patients in two primary health centers (
n
= 63) were included. Hospitalized patients were significantly more often male (64 vs 40%) and older (66 vs 43 years old in median) and had significantly more comorbidities than outpatients. Hyposmia and hypogeusia were reported by 33% of patients and occurred significantly less frequently in hospitalized patients (12% and 13%, respectively) than in the health centers’ outpatients (33% and 43%, respectively) and in the hospital outpatients (65% and 60%, respectively). Hyposmia and hypogeusia appeared more frequently after other COVID-19 symptoms. Patients with hyposmia and/or hypogeusia were significantly younger and had significantly less respiratory severity criteria than patients without these symptoms. Olfactory and gustatory dysfunction occurs frequently in COVID-19, especially in young, non-severe patients. These symptoms might be a useful tool for initial diagnostic work-up in patients with suspected COVID-19.
Monkeypox virus (MPXV) is currently spreading among men who have sex with men, outside of sub-Saharan Africa, and close contact during sex seems to be one of the key pathways of viral transmission in ...the current outbreak. Our aim was to describe the distribution of MPXV in the human body, as it might play a role in its dissemination through sexual contact.
The study population in this case series consisted of patients with confirmed MPXV infection attending the Pitié-Salpêtrière Hospital (Paris, France), who had been sampled from multiple anatomical sites, including skin, anus, throat, blood, urine, and semen, at diagnosis and 2 weeks later. We compared the proportion of positive samples and MPXV viral loads (given as PCR cycle thresholds Ct) between anatomical sites, and between day 0 (D0) and D14.
Overall, 356 samples were collected between May 20 and June 13, 2022, from 50 men with a median age of 34 years (IQR 29–40). 22 (44%) of the 50 men were classified as HIV-negative on day (D)0, and 22 (44%) were living with HIV. At D0, MPXV detection was more frequent from skin (44 88% of 50), anus (30 71% of 42), and throat (36 77% of 47) than from blood (13 29% of 45), urine (nine 22% of 41), or semen (13 54% of 24). Viral loads were significantly higher from skin lesions (Ct 19·8) and anal samples (Ct 20·9) than from throat (Ct 27·2), blood (Ct 32·8), urine (31·1), or semen samples (Ct 27·8). When analysing the 107 samples taken from 24 patients at D14, the proportion of positive samples strongly decreased between D0 and D14 at all sites: skin (four 22% of 18), anus (two 9% of 22), throat (none of 21), blood (one 5% of 21), urine (none of 14), and semen (two 9% of 11).
These data contribute to a better understanding of how the virus might spread between sexual partners over a relatively short period of time. High MPXV viral loads from skin and mucosa, including genital and anal sites, suggest that transmission most likely occurs through direct body contact rather than through the respiratory route or contact with body fluids, which should help to refine the prevention messages delivered to individuals most exposed to the virus.
None.
Abstract
Background
Although some integrase strand transfer inhibitors (INSTIs) promote peripheral and central adipose tissue/weight gain in people with human immunodeficiency virus (PHIV), the ...underlying mechanism has not been identified. Here, we used human and simian models to assess the impact of INSTIs on adipose tissue phenotype and function.
Methods
Adipocyte size and fibrosis were determined in biopsies of subcutaneous and visceral adipose tissue (SCAT and VAT, respectively) from 14 noninfected macaques and 19 PHIV treated or not treated with an INSTI. Fibrosis, adipogenesis, oxidative stress, mitochondrial function, and insulin sensitivity were assessed in human proliferating or adipocyte-differentiated adipose stem cells after long-term exposure to dolutegravir or raltegravir.
Results
We observed elevated fibrosis, adipocyte size, and adipogenic marker expression in SCAT and VAT from INSTI-treated noninfected macaques. Adiponectin expression was low in SCAT. Accordingly, SCAT and VAT samples from INSTI-exposed patients displayed higher levels of fibrosis than those from nonexposed patients. In vitro, dolutegravir and, to a lesser extent, raltegravir were associated with greater extracellular matrix production and lipid accumulation in adipose stem cells and/or adipocytes as observed in vivo. Despite the INSTIs’ proadipogenic and prolipogenic effects, these drugs promoted oxidative stress, mitochondrial dysfunction, and insulin resistance.
Conclusions
Dolutegravir and raltegravir can directly impact adipocytes and adipose tissue. These INSTIs induced adipogenesis, lipogenesis, oxidative stress, fibrosis, and insulin resistance. The present study is the first to shed light on the fat modifications observed in INSTI-treated PHIV.
Some integrase strand transfer inhibitors promote peripheral and central fat/weight gain in people with HIV. We used unique simian and human adipose tissue models and in vitro adipocytes and revealed that dolutegravir and raltegravir induced adipogenesis, oxidative stress, lipogenesis, fibrosis, and insulin resistance.
Abstract
Background
There is no precise idea whether patients with chronic symptoms attributed to Lyme borreliosis (LB) have LB or another disease.
Methods
We evaluated patients consulting for a ...presumed LB with a holistic approach including presumptive treatment. We included symptomatic patients consulting for presumed LB. They were classified as confirmed LB when they met four criteria, and possible LB if three with a positive clinical response to presumptive treatment.
Results
Amongst the 301 patients, 275 (91%) were exposed to tick bites, and 165 (54%) were bitten by a tick. At presentation, 151 patients (50.1%) had already been treated with a median of one (1–22) course of antimicrobials, during 34 (28–730) days. Median number of symptoms was three (1–12) with a median duration of 16 (1–68) months. Median number of signs was zero (0–2). ELISA was positive in 84/295 (28.4%) for IgM and 86/295 (29.1%) for IgG, and immunoblot was positive in 21/191 (10.9%) for IgM and 50/191 (26.1 %) for IgG. Presumptive treatment after presentation failed in 46/88 patients (52%). Diagnosis of LB was confirmed in 29 patients (9.6%), and possible in 9 (2.9%). Of the 243 patients with non-LB diagnosis, diseases were psychological, musculoskeletal, neurological or other origin in 76 (31.2%), 48 (19.7%), 37 (15.2%) and 82 (33.7%) patients respectively. Patients with other diseases were significantly younger, having more symptoms, longest duration of symptoms, less clinical signs and less frequent LB positive serologies.
Conclusions
Overdiagnosis and overtreatment of LB is worsening. Health authorities should investigate this phenomenon.
In about 300 patients who consulted for presumed Lyme borreliosis, this diagnosis was confirmed in fewer than 10%, whereas 80% were found to have another disease. Overall, the presumptive treatment administered before or after referral failed in about 80%.
HIV infection has become a chronic disease, with a lower mortality, but a consequent increase in age-related noninfectious comorbidities. Metabolic disorders have been linked to the effect of cART as ...well to the effects of immune activation and chronic inflammation. Whereas it is known that aging is intrinsically associated with hyperinflammation and immune system deterioration, the relative impact of chronic HIV infection on such inflammatory and immune activation has not yet been studied focusing on an elderly HIV-infected population.The objectives of the study were to assess 29 blood markers of immune activation and inflammation using an ultrasensitive technique, in HIV-infected patients aged ≥75 years with no or 1 comorbidity (among hypertension, renal disease, neoplasia, diabetes mellitus, cardiovascular disease, stroke, dyslipidemia, and osteoporosis), in comparison with age-adjusted HIV-uninfected individuals to identify whether biomarkers were associated with comorbidities. Wilcoxon nonparametric tests were used to compare the levels of each marker between control and HIV groups; logistic regression to identify biomarkers associated to comorbidity in the HIV group and principal component analysis (PCA) to determine clusters associated with a group or a specific comorbidity.A total of 111 HIV-infected subjects were included from the Dat'AIDS cohort and compared to 63 HIV-uninfected controls. In the HIV-infected group, 4 biomarkers were associated with the risk of developing a comorbidity: monocyte chemoattractant protein-1 (MCP-1), neurofilament light chain (NF-L), neopterin, and soluble CD14. Six biomarkers (interleukin IL-1B, IL-7, IL-18, neopterin, sCD14, and fatty acid-binding protein) were significantly higher in the HIV-infected group compared to the control group, 11 biomarkers (myeloperoxydase, interleukin-1 receptor antagonist, tumor necrosis factor receptor 1, interferon-gamma, MCP-1, tumor necrosis factor receptor 2, IL-22, ultra sensitivity C-reactive protein, fibrinogen, IL-6, and NF-L) were lower. Despite those differences, PCA to determine clusters associated with a group or a specific comorbidity did not reveal clustering nor between healthy control and HIV-infected patients neither between the presence of comorbidity within HIV-infected group.In this highly selected geriatric HIV population, HIV infection does not seem to have an additional impact on age-related inflammation and immune disorder. Close monitoring could have led to optimize prevention and treatment of comorbidities, and have limited both immune activation and inflammation in the aging HIV population.