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.

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.

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.

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.

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.

Bone loss in patients with HIV infection.

The prognosis of HIV infection has been considerably improved by the introduction of antiretroviral drugs. However, the longer survival times are associated with the emergence of new complications including decreased bone mineral density (BMD) values and/or bone insufficiency fractures. A meta-analysis of studies published between 1966 and 2005 showed bone absorptiometry results indicating osteoporosis in 15% of HIV patients and osteopenia in 52%. Longitudinal studies found no evidence that antiretroviral drug therapy contributed to the occurrence of bone loss. Available data indicate uncoupling with increases in bone resorption markers and decreases in bone formation markers. In addition to conventional risk factors for osteoporotic fractures, factors in HIV-infected patients may include malnutrition (wasting syndrome), hypogonadism, disorders in calcium and phosphate metabolism, and HIV infection per se. In patients with established bone insufficiency, bisphosphonate therapy should be considered. Alendronate in combination with vitamin D and calcium supplementation has been found effective in improving BMD values.

Impact of HIV infection on severity of imported malaria is restricted to patients with CD4 cell counts < 350 cells/microl.

OBJECTIVES: To study the relative impact of HIV-1 infection and associated immunodepression on the severity of Plasmodium falciparum malaria in adults returning from areas of endemic malaria. METHODS: We conducted a cross-sectional study, based on data from 104 HIV-infected patients from the French Hospital Database on HIV cohort (FHDH-ANRS CO4) and 161 HIV-negative patients from Bichat hospital, with a diagnosis of imported P. falciparum malaria between 2000 and 2003. The severity of falciparum malaria episode was graded with World Health Organization (WHO) criteria 2000 or on 2007 French recommendations. RESULT: Depending on criteria used, 40% (WHO) and 28% (2007 French recommendations) of episodes of imported P. falciparum malaria in HIV-infected patients were classified as severe, compared with 21% (WHO) and 11% (2007 French recommendations) of episodes among HIV-negative patients. Among HIV-infected patients, the episodes were severe in between 22 (CD4 cell counts > or =350/microl) and 51% (CD4 cell counts <350/microl) of cases using WHO criteria, and between 12 (CD4 cell counts > or =350/microl) and 41% (CD4 cell counts <350/microl) of cases using 2007 French recommendations criteria. Relative to HIV-negative patients, after adjusting for confounding factors, HIV-infected patients with severe immunodepression (CD4 cell counts <350/microl) were at a significantly higher risk of severe malaria than HIV-negative patients (odds ratio 3.2-4.7, depending on the criteria) contrary to HIV-infected patients with CD4 cell counts more than 350/microl (odds ratio 0.7-0.9). CONCLUSION: The association between HIV infection and severity of imported P. falciparum malaria is only observed for HIV-infected patients with severe immunodepression (CD4 cell counts <350/microl).

Imported malaria in HIV-infected patients enrolled in the ANRS CO4 FHDH study.

BACKGROUND: To describe episodes of imported malaria in human immunodeficiency virus type 1-infected patients and to study the risk factors for severe Plasmodium falciparum malaria. METHODS: Patients enrolled in the French Hospital Database on HIV who were diagnosed with a first episode of malaria between 1996 and 2003 were included. The severity of P. falciparum imported malaria was graded with World Health Organization criteria. Geographic areas were classified according to P. falciparum chemoresistance. Risk factors for severe malaria were identified with logistic regression. RESULTS: We studied 190 patients infected by P. falciparum in 178 cases. All but four of the patients were infected in sub-Saharan Africa, and half were returning from a country with a high P. falciparum chloroquine resistance. Their median age was 37.5 years, and 57% came from a country endemic with malaria. The median CD4 cell count was 299/mm, and the median plasma human immunodeficiency virus type 1 RNA load was 4.5 log10 copies/mL. Sixty-five (36.5%) episodes of P. falciparum malaria were severe. Severe imported malaria was associated with CD4 cells/mm <350 (odds ratio = 2.58; 95% confidence interval: 1.19 to 5.57). The risk of severe malaria was lower in patients returning from a country with a high prevalence of chemoresistance (odds ratio = 0.50; 95% confidence interval: 0.25 to 0.99). CONCLUSIONS: Severe imported malaria in human immunodeficiency virus type 1-infected patients is associated with decreased CD4 cell count. The risk seems lower when P. falciparum infection was acquired in areas of high prevalence of chemoresistance.

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.

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.