Impact of the COVID-19 pandemic on sexual behaviour and welfare of HIV preexposure prophylaxis users: a mixed-method study.

COVID-19 pandemic can affect people using HIV preexposure prophylaxis (PrEP). To assess its consequences on PrEP users' sexual behaviour and welfare, we conducted a mixed-method study. A self-administered questionnaire was given to PrEP users during scheduled consultation in Tourcoing Hospital from February to May 2021. In addition, a qualitative study included 14 participants who took part in semi-structured in-depth interviews (IDIs). Ninety-four PrEP users completed the questionnaire. During lockdown, 62% of participants continued PrEP. After lockdown release, the average number of sexual intercourses and partners increased from 6 ± 12 to 13 ± 17 intercourses/month (p < 0.001) and from 3 ± 11 to 11 ± 34 partners/month (p < 0.001). Similarly, the proportion of PrEP users who engaged in group sex, sex with alcohol or chemsex increased respectively from 28% to 55% (p < 0.001), 28% to 45% (p < 0.001) and 28% to 38% (p < 0.001). Analysis of IDIs revealed emotional deprivation and sexual frustration during the lockdown. After its release, frequent clandestine chemsex parties and curfew forcing overnight stay increased fears of intimate violence and overdoses. In conclusion, PrEP users reduced their sexual activity during the lockdown. Its release led to an increase in sexual risk-taking. Social distancing measures could favour medical and social harm of sexual risk-taking.

High Frequency of Specific Polysaccharide Antibody Deficiency in Adults With Unexplained, Recurrent and/or Severe Infections With Encapsulated Bacteria.

BACKGROUND: Primary immunodeficiencies (PIDs) in adults are mainly revealed by recurrent and/or severe bacterial infections. The objective of this study was to evaluate a systematic research strategy of PIDs in adults with unexplained bacterial infections, with a special focus on specific polysaccharide antibody deficiency (SPAD). METHODS: In this prospective multicenter study, inclusion criteria were recurrent benign upper and lower respiratory tract infections (RTIs) for at least two years (group 1), at least one upper or lower RTI requiring hospitalization (group 2), and/or at least one invasive infection documented with encapsulated bacteria (group 3). Main exclusion criteria were all local and general conditions that could explain infections. If no PID diagnosis was made, response to polysaccharide antigens was assessed using a pneumococcal polysaccharide vaccine. RESULTS: From March 2015 to March 2020, 118 patients were included (37 males, median age of 41 years): 73, 17, and 28 in groups 1, 2, and 3, respectively. Forty-seven PIDs were diagnosed, giving an estimated frequency of 39.8% (95% confidence interval [CI] [30.4, 48.8]). SPAD was the most frequent diagnosis by far (n = 37/47, 78.7%), and was made in 23, 5, and 9 patients from groups 1 to 3, respectively. All SPAD patients received conjugate vaccines and, according to their infectious history, were on surveillance or treated with preventive antibiotics (n = 6) and/or with immunoglobulins replacement therapy (n = 10), the latter being dramatically efficient in all cases. CONCLUSIONS: Considering its high prevalence among adults with unexplained recurrent and/or severe bacterial infections, SPAD should be screened in those patients. CLINICAL TRIALS REGISTRATION: NCT02972281.

Clinical and virological features of acute hepatitis A during an ongoing outbreak among men who have sex with men in the North of France.

OBJECTIVES: Since February 2017, an increase of acute hepatitis A (AHA) cases has been notified in North of France. We aimed to report clinical and virological features of 49 cases treated in three hospitals in Lille European Metropolis (LEM). METHODS: All adult patients treated for AHA in 3 LEM hospitals between 20 February and 5 July 2017 were included. Demographic characteristics, exposure risk factors to hepatitis A virus (HAV), AHA manifestations and concomitant sexually transmitted infections (STI) were retrospectively recorded. RESULTS: Forty-nine cases of AHA were diagnosed among which 34 (69%) were hospitalised. Severe AHA occurred in 7 (14%) patients. The median age of cases was 36 years. All cases except 1 were men and 32 (65%) were identified as men having sex with men (MSM). Eleven (23%) patients were HIV-infected, 5 were under HIV pre-exposure prophylaxis (PrEP), 6 had a history of HIV postexposure prophylaxis and 19 had a history of at least one STI. Only three patients had received HAV vaccine. Proportion of patients tested for syphilis, chlamydial and gonococcal infections was 75% (18/24) in those seen by sexual health specialists and 21% (6/29) in those seen by other specialists. At least one concomitant STI was diagnosed in 13 out of 24 tested patients (54%). RT-PCR sequencing was available for 38 cases and confirmed co-circulation of 3 different strains of subgenotype IA (VRD 521 2016: n=24, RIVM-HAV16-090: n=13, V16-25801: n=1), already identified in several European countries. CONCLUSIONS: We are facing an outbreak of AHA among MSM in the North of France with a high rate of hospitalisation. Analysis of cases highlighted missed opportunities of vaccination and lack of concomitant STI screening. Awareness among healthcare providers and MSM should be increased and HAV vaccination promoted.

Impact and Tolerance of Immunosuppressive Treatments in Patients Living with HIV with Inflammatory or Autoimmune Diseases.

BACKGROUND: Patients living with HIV (PLWHIV) can develop autoimmune diseases (AD) needing immunosuppressive treatments (IST). This study aims to describe the impact of IST in PLWHIV. METHODS: This was a multicentric retrospective observational study in six HIV referral centers on PLWHIV under IST for AD. Demographic factors, viral co-infections, immunovirological status before and under IST, infectious events, and their descriptions were collected and described focusing on infectious events, immunovirological variations, and IST effectiveness. RESULTS: 9480 PLWHIV were screened for inclusion. Among them, 138 (1.5%) had a history of auto-immune disease, among which 32 (23%) received IST. There was mainly spondyloarthropathy (28%) and the most commonly used IST was methotrexate. The median follow-up under IST was 3.8 years (2.7; 5.9). There were 15 infectious events (0.5 events/individuals) concerning nine patients. At the last medical follow-up, 81% of these were in remission of their AD. Under IST, there was an increase in CD4 during follow-up (629 vs. 827 CD4/mm3, p = 0.04). No HIV virological failure was noted. CONCLUSIONS: This study supports a growing evidence base that IST can be used safely and effectively in PLWHIV with careful monitoring.

A rare case of invasive non-typeable Haemophilus influenzae spondylodiscitis and periprosthetic joint infection.

A non-typeable Haemophilus influenzae (NTHi) was responsible for an invasive infection including bacteremia, spondylodiscitis with epidural abscess, and periprosthetic hip infection in a 79-year-old woman, triggered by a superinfected ethmo-orbital mucocele. Surgical drainage and antibiotic therapy allowed recovery. PET-scan full cartography of NTHi infection dissemination enabled the discovery of spondylodiscitis. This rare cause of spondylodiscitis and periprosthetic joint infection suggests a complete work-up is unavoidable.

In vivo effect of adhesion inhibitor heparin on Legionella pneumophila pathogenesis in a murine pneumonia model.

OBJECTIVE: To examine the effect of intratracheal heparin instillation on Legionella pneumophila-related acute lung injury (ALI) and systemic dissemination. DESIGN: Prospective, controlled experimental study. SETTING: University research laboratory. INTERVENTIONS: A/J mice received 5 microg of sulfated heparin intratracheally co-instilled with 10(6) or 10(8) colony-forming units (CFU) of a virulent isolate of L. pneumophila. MEASUREMENTS AND RESULTS: ALI was assessed in control groups (PBS and PBS-heparin) and on days 1, 2 and 3 post-infection, in terms of the lung wet-to-dry (W/D) weight ratios and of lung endothelial permeability to radio-labeled albumin (Perm-I(125)). Lung bacterial loads were measured and systemic spread was assessed by blood and target organ culture. The alveolar inflammatory response was evaluated by measuring the cytokine levels (TNF-alpha, IFN-gamma, IL-6 and IL-12p70) in bronchoalveolar lavage fluids (BALF). Co-instilled heparin improved mouse survival after the 10(8) CFU challenge (p < 0.01). On day 2, heparin co-instillation significantly reduced the W/D ratio and Perm-I(125) (p < 0.01 and p < 0.001 respectively), improved lung bacterial clearance (p < 0.001), prevented systemic dissemination (blood, liver, spleen, kidneys and brain cultures, all p < 0.05) and significantly increased IFN-gamma and IL-12p70 levels in BALF (p < 0.05). CONCLUSIONS: Heparin co-instillation during intratracheal L. pneumophila challenge has a protective effect on the alveolar-capillary barrier and prevents bacterial dissemination. These results tend to confirm the competitive inhibition by heparin of L. pneumophila attachment to lung epithelium in vivo, and point to the possible involvement of a heparan-sulfate adhesin in L. pneumophila binding to pneumocytes.

Reduced bone mineral density among HIV-infected, virologically controlled young men: prevalence and associated factors.

OBJECTIVE: Reduced bone mineral density (BMD) is a frequent comorbidity observed in people living with HIV (PLHIV). We aimed to determine the prevalence of reduced BMD and its associated factors among young PLHIV men, virologically controlled by combination antiretroviral therapy (cART). DESIGN: A bicentric cross-sectional study. METHODS: We selected men, aged less than 50 years, treated by cART, with HIV-RNA less than 50 copies/ml. BMDs of lumbar spine and hip were measured by dual-energy X-ray absorptiometry (DXA). A Z-score at either site between -1.0 and -2.0 or -2 or less defined osteopenia or osteoporosis, respectively. Linear and polytomous logistic regression analyses were performed. RESULTS: Among 230 men with a median age of 43 [interquartile range (IQR), 36-47] years, BMI of 23.5 (21.3-25.3) kg/m(2) and median duration of cART of 4.2 (1.7-8.5) years, reduced BMD was diagnosed in 48.3%. In multivariate analyses, BMI decrease was associated with a risk of osteopenia [odds ratio (OR) = 1.17, P < 0.01] and osteoporosis (OR = 1.24, P < 0.01). Oestradiol levels decrease were associated with osteoporosis (OR = 1.32, P < 0.05) and lower lean mass with osteopenia (OR = 2.98, P < 0.01). There was a protective effect of the duration of cART (OR = 0.87, P < 0.01), which was even greater when the duration was more than 3 years (OR = 0.44, P = 0.02). CONCLUSION: There is a high prevalence of reduced BMD among young men, despite persistent virological control of HIV-infection. This observation raises the question of extending current recommendations for BMD assessment to PLHIV aged < 50 years for whom BMD has stabilized after cART initiation, i.e. treated for more than three years.

Inhaled nitric oxide increases endothelial permeability in Pseudomonas aeruginosa pneumonia.

OBJECTIVE: Pneumonia is a frequent cause of acute respiratory distress syndrome (ARDS), and Pseudomonas aeruginosa is a leading pathogen in nosocomial pneumonia. The management of ARDS remains a major problem, and only a limited number of options can improve the oxygenation. Inhaled nitric oxide (iNO) has been widely used, although this molecule is a free radical potentially harmful through the generation of toxic radical derivatives. The goal of our study was to assess the consequences of iNO (10 ppm) in a rat model of P. aeruginosa-induced lung injury. DESIGN: The animals were exposed for 24 h to iNO after instillation of the pathogen. Distal alveolar fluid clearance (DAFC) and epithelial and endothelial permeability were measured with a double flux of radio-labeled albumin. RESULTS: DAFC and epithelial permeability were increased in pneumonia but not influenced by iNO. In contrast, endothelial permeability was statistically significantly higher in the pneumonic animals exposed to iNO than in the pneumonic group without iNO (0.24+/-0.03 vs 0.47+/-0.1, p<0.05). This increase was not related to the production of nitrate/nitrite, nor to the increase of the inflammatory response evaluated by cytokine levels in the bronchoalveolar lavage fluid (TNF-alpha, IL-6, IL-10). The alveolar recruitment of polymorphonuclear neutrophils was comparable in the pneumonic group exposed to iNO and the pneumonic group without iNO. CONCLUSION: iNO increases the endothelial permeability in P. aeruginosa pneumonia. The mechanism is not related to the production of nitrate/nitrite or to a greater inflammatory response.

[When to initiate antiretroviral therapy and what to start with?]. / Ouand et comment commencer un traitement antirétroviral?

The decision to initiate antiretroviral therapy is influenced by the assessment of potential benefits and risks associated with early versus deferred therapy. The potential risks of deferred therapy include the increase probability of progression to AIDS, and the possibility that damage to the immune system would be irreversible. The potential benefits of deferred treatment are avoidance of drug-related toxicities and treatment-related negative effects on quality of life; preservation of treatment options, and more time for the patient to have a greater understanding of treatment demands. Once the decision is made, the primary goals of antiretroviral therapy are to reduce HIV-related morbidity and mortality, improve quality of life, restore and preserve immunologic function, and maximally and durably suppress viral load. However, regimen selection should be individualized, taking into consideration a number of factors such as pre-treatment viral load and CD4 lymphocyte cell count, co-morbidities, adherence potential, dosing convenience regarding pill burden, potential adverse drug effects, and potential drug interactions with other medications.

Impact of human immunodeficiency virus type 1 subtype on first-line antiretroviral therapy effectiveness.

OBJECTIVE: The effectiveness of antiretroviral treatment (ART) was compared in 416 naive patients from a French clinical cohort infected with B and non-B HIV-1 subtypes. METHODS: Time to HIV viral load (VL) undetectability was calculated for each subtype group. Three other parameters were estimated 3, 6 and 12 months after enrolment: clinical progression (that is, AIDS-defining events or death), changes in CD4 cell counts from baseline and proportion of patients achieving an undetectable VL (<400 HIV-RNA copies/ml). RESULTS: In this cohort, 317 patients (76%) were infected with a B subtype and 99 (24%) with a non-B subtype. Median time to VL undetectability was similar in the B subtype group [147 days, 95% confidence interval (CI) 119-165] and non-B subtype group (168 days, 95% CI: 105-234; P=0.16). After adjusting for AIDS-defining events at enrolment, baseline CD4 cell counts and VL, and for the treatment on which patients were initiated, no association was found between HIV subtypes and time to VL undetectability (B subtype vs non-B subtype: hazard ratio=0.80, 95% CI: 0.62-1.02, P=0.07). In the 3, 6 and 12 months after enrolment, subtype had no impact on clinical progression, CD4 cell count or VL responses to ART. This suggests that B and non-B subtypes do not affect first-line therapy efficacy, which is encouraging in view of the worldwide spread of non-B HIV-1 subtypes and the increasing availability of ART in developing countries. However, in this study we did not take into account individual non-B subtype species, therefore further studies should be designed to evaluate the efficacy of these regimens in patients with particular non-B subtypes.

Pneumocystis jiroveci (carinii) pneumonia following initiation of infliximab and azathioprine therapy in a patient with Crohn's disease.

Anti-TNFalpha therapy is an effective treatment of Crohn's disease. There is an increased risk of infection, including atypical infection associated in infliximab treated patients. We report a case of a young man who developed Pneumocystisjiroveci pneumonia shortly after starting therapy with infliximab. Thus, although rare, prophylaxis against Pneumocystis jiroveci pneumonia might be considered when starting a treatment with infliximab, especially in patients receiving concomitant immunosuppressive agents.

Ventilation-induced lung injury is associated with an increase in gut permeability.

Mechanical ventilation is associated with several harmful effects mainly related to high tidal volumes (Vt). Ventilator-induced lung injury can be responsible for an increased production of inflammatory mediators. We evaluated remote consequences on the gut of lung triggered inflammatory response, neutralizing anti-tumor necrosis factor (TNF) antibody was administered to assess the role of TNF in lung and gut permeability changes. Rats were anesthetized and ventilated for 2 h. A control group (Con: Vt = 10 mL/kg) was compared with a high Vt group (HV: Vt = 30 ml/kg). One microCi of I125-labeled human serum albumin was injected to measure extravascular albumin space. Gut permeability was evaluated by plasma-to-lumen ratio leakage of I125 human serum albumin. Extravascular albumin space increased in the HV group from 446 +/- 50 microL to 2783 +/- 887 microL. Gut index of permeability increased from 5.1 +/- 1.2 to 14.2 +/- 4.9. Anti-TNF antibody prevented both lung and gut increase in permeability. High tidal volume ventilation resulted in an increase in lung edema and gut permeability, antagonism of TNF with neutralizing antibodies abrogated the increase in gut permeability as well as lung edema.

Apoptosis inhibition in P. aeruginosa-induced lung injury influences lung fluid balance.

OBJECTIVE: Pseudomonas aeruginosa-induced lung injury is characterized not only by the alteration in lung fluid movement but also by apoptosis of lung epithelial and endothelial cells. We studied whether inhibition of apoptosis using a broad spectrum caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp fluoromethylketone (Z-VAD.fmk), would affect lung fluid balance in rat P. aeruginosa pneumonia. METHODS: Z-VAD.fmk (3 mg/kg) was administered intravenously simultaneously with P. aeruginosa intratracheal instillation (0.5 ml/kg, 2 x 10(9) CFU/ml). Apoptosis was evaluated with the TUNEL technique, cytoplasmic oligonucleosome assay, and caspase 3 activation. To evaluate lung permeability, extravascular plasma equivalent (EPE) and lung wet to dry weight ratio (W/D) were measured 4 h after intratracheal instillation of P. aeruginosa. RESULTS: We found an increase of lung apoptosis 4 h after P. aeruginosa instillation: cytoplasmic oligonucleosome assay increased from 3.17+/-0.78 to 26.82+/-4.67 ODx1000/mg of proteins/ml, Z-VAD.fmk administration decreased this parameter to 10.3+/-2.98 ODx1000/mg of proteins/ml. Caspase 3 levels followed the same pattern. Apoptosis involved both epithelial cells and endothelial cells. Endothelial permeability was increased after Pseudomonas instillation: W/D increased from 3.75+/-0.28 in the Co group to 4.42+/-0.23 in the Pn group; EPE was also higher in the Pn group compared with the Co group (0.125+/-0.04 and 0.002+/-0.01 ml, respectively). Both of these parameters were improved after Z-VAD.fmk administration; W/D decreased to 3.36+/-0.25 and EPE to 0.02+/-0.02 ml. CONCLUSION: Apoptosis occurs in the early phase of P. aeruginosa pneumonia. Administration of Z-VAD.fmk significantly decreases DNA fragmentation and caspase 3 levels. This is associated with an improvement of endothelial permeability and lung fluid balance.

Hyperlactataemia during antiretroviral therapy: incidences, clinical data and treatment.

Lactic acidosis is a serious complication of antiretroviral therapy. Symptomatic hyperlactataemia is a milder form of this syndrome, but its incidence is unclear. In this prospective ongoing observational study of a large cohort of HIV-infected adults, hyperlactataemia was diagnosed in 64 patients. Incidences were 18.3/1000 person-years with antiretroviral therapy, and 35.8/1000 person-years for stavudine (d4T) regimens. Ten of the 64 patients developed lactic acidosis during the first 13 months of treatment (incidence 2.9/1000 treated person-years). In four of ten patients, symptoms were absent or mild. More patients on d4T first-line therapy developed lactic acidosis than patients previously treated with other drugs (p = 0.008). Despite the occurrence of one death, the subsequent outcome for the remaining patients was favourable after antiretroviral therapy was stopped and supportive treatment with vitamins and antioxidants initiated. The early diagnosis of cases was the result of great vigilance and, combined with routine measurements of the anion gap, might be the most crucial factor explaining the low mortality rate observed here.

Cohort Profile: French hospital database on HIV (FHDH-ANRS CO4).

The French Hospital Database on HIV (FHDH) is a hospital-based multicentre open cohort with inclusions ongoing since 1989. The research objectives focus mainly on mid- and long-term clinical outcomes and therapeutic strategies, as well as severe AIDS and non-AIDS morbidities, and public health issues relative to HIV infection. FHDH also serves to describe HIV-infected patients receiving hospital care in France. FHDH includes data on more than 120,000 HIV-infected patients from 70 French general or university hospitals distributed throughout France. Patients are eligible for inclusion if they are infected by HIV-1 or HIV-2 and give their written informed consent. Standardized variables are collected at each outpatient visit or hospital admission during which a new clinical manifestation is diagnosed, a new treatment is prescribed or a change in biological markers is noted, and/or at least every 6 months. Since its inception, variables collected in FHDH include demographic characteristics, HIV-related biological markers, the date and type of AIDS and non AIDS-defining events, antiretroviral treatments and the date and causes of death, as reported in the medical records. Since 2005, data have also been collected on: co-infection with hepatitis B or C virus; alcohol and tobacco use; and non HIV-related biomarkers. Anyone can submit a research project by completing a standardized form available on the FHDH website (http://www.ccde.fr/_fold/fl-1385734776-429.pdf) or from the corresponding author, describing the context and objectives of the study. All projects are reviewed by the scientific committee.

Risk of Kaposi sarcoma during the first months on combination antiretroviral therapy.

OBJECTIVE: To determine whether incident AIDS-defining Kaposi sarcoma or Pneumocystis jiroveci pneumonia (PJP) is associated with combination antiretroviral therapy (cART) initiation. DESIGN: Compare risk for Kaposi sarcoma and PJP by time on cART and CD4 reconstitution. METHODS: : In the FHDH-ANRS CO4 cohort (N = 66 369), Kaposi sarcoma (N = 1811) and PJP (N = 1718) incidence rates were computed by demographic and HIV strata. Crude and adjusted relative risk (RR) with 95% confidence intervals (CIs) following cART initiation were calculated by Poisson regression with untreated patients during 1996-2009 as reference. CD4 cell counts were compared by Wilcoxon rank sum tests. RESULTS: The risk of Kaposi sarcoma was very high during months 1-3 on cART (N = 160, RRCrude 3.94, 95% CI 3.26-4.76), which was incompletely attenuated by adjustment for demographics and contemporaneous CD4 cell count (RRAdj 1.25, 95% CI 1.02-1.53). Corresponding PJP risk was minimally elevated (N = 84, RRCrude 1.80, 95% CI 1.42-2.30) and markedly reduced with adjustment on the same variables and PJP prophylaxis (RRAdj 0.52, CI 0.41-0.67). HIV load had no added effect. Median CD4 cell count at cART initiation was much lower in patients with incident Kaposi sarcoma (82 cells/µl) or PJP (61 cells/µl) within 3 months than in those who did not develop these conditions (>250 cells/µl). Notably, median CD4 cell count change was +44 cells/µl per month with incident Kaposi sarcoma within 3 months of cART initiation versus 0 cells/µl per month with incident PJP (P = 0.0003). CONCLUSION: Failure of CD4 cell count reconstitution during months 1-3 on cART fully accounted for incident PJP. In contrast, there were 1.6 additional Kaposi sarcoma cases per 1000 person-years during months 1-3 on cART, suggesting that immune reconstitution may contribute to the risk for AIDS-defining Kaposi sarcoma.