Incidence and factors associated with PrEP discontinuation in France.

OBJECTIVES: HIV pre-exposure prophylaxis (PrEP) is effective in preventing HIV, but some seroconversions occur due to poor adherence or PrEP discontinuation. Our objective was to estimate the incidence of PrEP discontinuation and describe the reasons and factors associated with discontinuations. METHODS: A retrospective cohort was conducted in three French hospitals between January 2016 and June 2022. PrEP users who attended at least twice within 6 months during study period were included and followed up until December 2022. The incidence rate of PrEP discontinuation was estimated by censoring lost to follow up individuals. Factors associated with PrEP discontinuations were identified using a multivariate Cox model. RESULTS: A total of 2785 PrEP users were included, with 94% men and 5% transgender people. Median age was 35 years. By December 2022, 653 users had stopped PrEP (24%). The incidence rate was 10.8 PrEP discontinuations for 100 person-years (PY). The main causes of discontinuation were being in a stable relationship (32%), and not judging the treatment useful anymore (12%). Individuals who discontinued PrEP were younger [<29, HR = 1.45 (1.17-1.80)], and more likely to be women [HR = 2.44 (1.50-3.96)] or sex workers [HR = 1.53 (0.96-2.44)]. They were more likely to report PrEP side effects [HR = 2.25 (1.83-2.77)] or ≥2 sexually transmitted infections [HR = 1.87 (1.53-2.27)] during the last year. CONCLUSION: The incidence of PrEP discontinuations was quite low compared to rates observed in other cohorts. Users who stopped PrEP were sometimes still exposed to HIV, emphasizing the need for targeted interventions to prepare and support PrEP discontinuations and limit seroconversion risk.

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.

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.

Clinical impact of tropism testing in a real-life cohort of HIV infected patients: a retrospective observational study.

BACKGROUND: The circumstances of prescription of tropism tests clinically relevant in treatment-experienced patients are unclear. METHODS: We performed a monocentric retrospective analysis of all tropism tests performed between 2006 and 2015 in HIV-infected patients on antiretroviral therapy (ART) without MVC. The motivation of tropism determination was collected. Factors associated with MVC prescription were determined using logistic regression analysis. RESULTS: Five hundred sixty-three tests were performed in experienced patients not receiving MVC. Reasons for tropism performance were: virological failure (44%), side effects or drug-interactions (37%), simplification or sparing strategies (11%), immunological failure (5%), and improvement of neurological diffusion (3%). MVC was prescribed in 110 cases (20%), though 366 tests (65%) revealed a tropism CCR5. MVC was more often prescribed before 2011 (OR 3.65, 95% CI 2.17-6.13) and in patients with multiple previous ART regimens (less than 4 ART regimens compare to more than 10 ART regimens (OR 0.34, 95% CI 0.15-0.74)). CONCLUSIONS: In experienced patients not receiving MVC, tropism test prescription should be restricted to patients with virological failure and limited therapeutic options such as patients already treated with a wide range of ART regimens.

Factors predictive of treatment failure in staphylococcal prosthetic vascular graft infections: a prospective observational cohort study: impact of rifampin.

BACKGROUND: There exists considerable debate concerning management of prosthetic vascular graft infection (PVGI), especially in terms of antimicrobial treatment. This report studies factors associated with treatment failure in a cohort of patients with staphylococcal PVGI, along with the impact of rifampin (RIF). METHODS: All data on patients with PVGI between 2006 and 2010 were reviewed. Cure was defined as the absence of evidence of infection during the entire post-treatment follow-up for a minimum of one year. Failure was defined as any other outcome. RESULTS: 84 patients (72 M/12 F, median age 64.5 ± 11 y) with diabetes mellitus (n = 25), obesity (n = 48), coronary artery disease (n = 48), renal failure (n = 24) or COPD (n = 22) were treated for PVGI (median follow-up was 470 ± 469 d). PVGI was primarily intracavitary (n = 47). Staphylococcus aureus (n = 65; including 17 methicillin-resistant S. aureus) and coagulase-negative Staphylocococcus (n = 22) were identified. Surgical treatment was performed in 71 patients. In univariate analysis, significant risk factors associated with failure were renal failure (p = 0.04), aortic aneurysm (p = 0.03), fever (p = 0.009), aneurysm disruption (p = 0.02), septic shock in the peri-operative period (p = 0.005) and antibiotic treatment containing RIF (p = 0.03). In multivariate analysis, 2 variables were independently associated with failure:septic shock [OR 4.98: CI 95% 1.45-16.99; p=0.01] and antibiotic containing rifampin [OR: 0.32: CI95% 0.10-0.96; p=0.04]. CONCLUSION: Results of the present study suggest that fever, septic shock and non-use of antibiotic treatment containing RIF are associated with poor outcome.

Should highly active antiretroviral therapy be prescribed in critically ill HIV-infected patients during the ICU stay? A retrospective cohort study.

BACKGROUND: The impact of highly active antiretroviral therapy (HAART) in HIV-infected patients admitted to the intensive care unit (ICU) remains controversial. We evaluate impact of HAART prescription in HIV-infected patients admitted to the ICU of Tourcoing Hospital from January 2000 to December 2009. RESULTS: There were 91 admissions concerning 85 HIV-infected patients. Reasons for ICU admission were an AIDS-related diagnosis in 46 cases (51%). Fifty two patients (57%) were on HAART at the time of ICU admission, leading to 21 immunovirologic successes (23%). During the ICU stay, HAART was continued in 29 patients (32%), and started in 3 patients (3%). Only one patient experienced an adverse event related to HAART. Mortality rate in ICU and 6 months after ICU admission were respectively 19% and 27%. Kaplan-Meier estimates of the cumulative unajusted survival probability over 6 months were higher in patients treated with HAART during the ICU stay (Log rank: p = 0.04). No benefit of HAART in ICU was seen in the adjusted survival proportion at 6 months or during ICU stay. Prescription of HAART during ICU was associated with a trend to lower incidence of new AIDS-related events at 6 months (respectively 17% and 34% with and without HAART, p = 0.07), and with higher incidence of antiretroviral resistance after ICU stay (respectively 25% and 7% with and without HAART, p = 0.02). CONCLUSIONS: Our results suggest a lower death rate over 6 months in critically ill HIV-infected patients taking HAART during ICU stay. The optimal time to prescribe HAART in critically ill patients needs to be better defined.

Outcome and predictors of treatment failure in total hip/knee prosthetic joint infections due to Staphylococcus aureus.

BACKGROUND: Variables associated with the outcome of patients treated for prosthetic joint infections (PJIs) due to Staphylococcus aureus are not well known. METHODS: The medical records of patients treated surgically for total hip or knee prosthesis infection due to S. aureus were reviewed. Remission was defined by the absence of local or systemic signs of implant-related infection assessed during the most recent contact with the patient. RESULTS: After a mean posttreatment follow-up period of 43.6 ± 32.1 months, 77 (78.6%) of 98 patients were in remission. Retention of the infected implants was not associated with a worse outcome than was their removal. Methicillin-resistant S. aureus (MRSA)-related PJIs were not associated with worse outcome, compared with methicillin-susceptible S. aureus (MSSA)-related PJIs. Pathogens identified during revision for failure exhibited no acquired resistance to antibiotics used as definitive therapy, in particular rifampin. In univariate analysis, parameters that differed between patients whose treatment did or did not fail were: American Society of Anesthesiologists (ASA) score, prescription of adequate empirical postsurgical antibiotic therapy, and use of rifampin combination therapy upon discharge from hospital. In multivariate analysis, ASA score ≤2 (odds ratio [OR], 6.87 [95% confidence interval {CI}, 1.45-32.45]; P = .04) and rifampin-fluoroquinolone combination therapy (OR, 0.40 [95% CI, 0.17-0.97]; P = .01) were 2 independent variables associated with remission. CONCLUSIONS: The results of the present study suggest that the ASA score significantly affects the outcome of patients treated for total hip and knee prosthetic infections due to MSSA or MRSA and that rifampin combination therapy is associated with a better outcome for these patients when compared with other antibiotic regimens.

Comparison of vancomycin and teicoplanin trough serum levels in patients with infected orthopedic devices: new data for old therapies.

We compared retrospectively vancomycin and teicoplanin trough serum levels after loading doses and, subsequently, after high daily doses, in 52 patients (26 in each group) who had developed infections after implantation of an orthopedic device. The target trough serum level was > 25 mg/l. Trough levels were significantly higher at 2 days (±1) and 5 days (±1) in patients who received teicoplanin compared with patients who received a continuous perfusion of vancomycin (26.1 vs. 16 mg/l at day 2 ± 1, P = 0.01; 27.8 vs. 19.9 mg/l at day 5 ± 1, P = 0.01). One of the 26 patients taking vancomycin reached the target trough serum level by day 2 (±1), whereas 10 of the 26 patients taking teicoplanin reached the target by that time (P = 0.002). At day 5 (±1), 6/26 patients taking vancomycin reached the target, versus 13/26 patients taking teicoplanin (P = 0.04). However, physicians should remain cautious when administering teicoplanin empirically because of the higher MIC90 values observed for coagulase-negative staphylococci compared with vancomycin.

Tolerability of prolonged linezolid therapy in bone and joint infection: protective effect of rifampicin on the occurrence of anaemia?

BACKGROUND: Linezolid therapy has shown high rates of clinical success in patients with osteomyelitis and prosthetic joint infections caused by Gram-positive cocci. Recent studies have demonstrated that linezolid/rifampicin combination therapy prevents the emergence of rifampicin-resistant mutations in vitro. However, linezolid/rifampicin combination-related haematological and neurological toxicities have not been evaluated. OBJECTIVES: To assess the tolerability of prolonged linezolid/rifampicin combination therapy compared with other linezolid-containing regimens in patients with bone and joint infections. METHODS: We reviewed the medical records of 94 patients who had received linezolid for >4 weeks after bone and joint infections. Anaemia was defined as a ≥2 g/dL reduction in haemoglobin, leucopenia as a total leucocyte count <4 × 10(9)/L, and thrombocytopenia as a reduction in platelet count to <75% of baseline. RESULTS: Anaemia was less frequent among patients on linezolid/rifampicin combination therapy than among patients on linezolid alone or in combination with other drugs (9.3%, 44% and 52%, respectively; P<0.01). In multivariate analysis, age and treatment group were independently associated with anaemia. Thrombocytopenia was reported in 44% of patients on linezolid/rifampicin combination therapy, in 48% of patients on linezolid alone and in 57.7% of patients on other linezolid-containing regimens. Age was the only variable associated with thrombocytopenia (P=0.019) in univariate analysis. CONCLUSIONS: Linezolid/rifampicin combination therapy was associated with a significantly reduced incidence of anaemia among patients with bone and joint infections, but it did not have an effect on thrombocytopenia and peripheral neuropathy rates. Linezolid/rifampicin combination therapy was not associated with poor clinical outcomes.

Culture of percutaneous bone biopsy specimens for diagnosis of diabetic foot osteomyelitis: concordance with ulcer swab cultures.

BACKGROUND: We assessed the diagnostic value of swab cultures by comparing them with corresponding cultures of percutaneous bone biopsy specimens for patients with diabetic foot osteomyelitis. METHODS: The medical charts of patients with foot osteomyelitis who underwent a surgical percutaneous bone biopsy between January 1996 and June 2004 in a single diabetic foot clinic were reviewed. Seventy-six patients with 81 episodes of foot osteomyelitis who had positive results of culture of bone biopsy specimens and who had received no antibiotic therapy for at least 4 weeks before biopsy constituted the study population. RESULTS: Pathogens isolated from bone samples were predominantly staphylococci (52%) and gram-negative bacilli (18.4%). The distributions of microorganisms in bone and swab cultures were similar, except for coagulase-negative staphylococci, which were more prevalent in bone samples (P < .001). The results for cultures of concomitant foot ulcer swabs were available for 69 of 76 patients. The results of bone and swab cultures were identical for 12 (17.4%) of 69 patients, and bone bacteria were isolated from the corresponding swab culture in 21 (30.4%) of 69 patients. The concordance between the results of cultures of swab and of bone biopsy specimens was 42.8% for Staphylococcus aureus, 28.5% for gram-negative bacilli, and 25.8% for streptococci. The overall concordance for all isolates was 22.5%. No adverse events--such as worsening peripheral vascular disease, fracture, or biopsy-induced bone infection--were observed, but 1 patient experienced an episode of acute Charcot osteoarthropathy 4 weeks after bone biopsy was performed. CONCLUSIONS: These results suggest that superficial swab cultures do not reliably identify bone bacteria. Percutaneous bone biopsy seems to be safe for patients with diabetic foot osteomyelitis.

Effectiveness and tolerability of prolonged linezolid treatment for chronic osteomyelitis: a retrospective study.

BACKGROUND: Linezolid is an oxazolidinone agent which is apparently well designed for treating chronic osteomyelitis, but data on effectiveness and tolerability as prolonged therapy is currently lacking. OBJECTIVE: The purpose of this study was to assess the effectiveness and tolerability of linezolid in the treatment of chronic osteomyelitis. METHODS: The charts of hospitalized patients who had been treated with linezolid for >4 weeks because of chronic osteomyelitis and were followed up for > or =12 months after the end of treatment were retrospectively reviewed for clinical outcome and tolerability. Cure was defined as the absence of clinical, biological, or radiological evidence of infection throughout the posttreatment follow-up. Linezolid tolerability was assessed on the basis of hematologic properties during treatment. RESULTS: Of the 66 patients included, all were white (mean [SD] age, 67.7 [18.1] years; 41 men and 25 women; mean [SD] weight, 80.7 [18.6] kg). Thirty-seven (56.1%) patients had infection due to implants including 27 prosthetic joints. Pathogens were predominantly methicillin-resistant staphylococci (49/72 strains, 68.1 %). Every patient was administered N linezolid (600 mg BID) treatment for 6 to 8 days as inpatients, and then, as outpatients, they were switched to PO treatment. Fifty (75.8%) patients received a combination of linezolid and other antimicrobial agents, including rifampin (32 [48.5%]). Surgery was performed in 52 (78.8%) patients. The median hospital stay was 14 days (mean [SD], 19 [11.4] days [range, 7-70 days] ). The median duration of treatment was 13 weeks (mean [SD], 14.3 [8.2] weeks [range, 5-36 weeks]). At the end of treatment, 56 (84.8%) patients were cured, and during the post-treatment follow-up (median duration, 15 months [range, 12-36 months]), 4 relapses occurred, resulting in an overall successful cure for 52 (78.8%) patients. Reversible anemia was reported in 21 patients (31.8%), of whom 16 (24.2%) required blood transfusions. Median time from treatment initiation to anemia onset was 7.3 weeks (range, 4-12 weeks). Peripheral neuropathy was reported in 6 (9.1%) patients, of whom 4 remained symptomatic for up to 24 months after linezolid discontinuation. Other reported adverse events included nausea (6 [9.1%]), diarrhea (1 [1.5%]), and headache (2 [3.0%]), although none of these patients discontinued treatment. CONCLUSIONS: In this retrospective chart review, treatment with linezolid as monotherapy or in combination with antimicrobials and/or surgery was associated with cure of chronic osteomyelitis in 84.8% of subjects at 12 weeks after the end of treatment and 78.8% at follow-up. Adverse events were reported in 51.5% of subjects, and 34.8% of subjects discontinued the study because of adverse events. The potential for severe complications justifies close monitoring of these patients.

Six-week versus twelve-week antibiotic therapy for nonsurgically treated diabetic foot osteomyelitis: a multicenter open-label controlled randomized study.

OBJECTIVE: Little is known about the optimal duration of antibiotic therapy for diabetic foot osteomyelitis (DFO). This study sought to compare the effectiveness of 6 versus 12 weeks of antibiotic therapy in patients with DFO treated nonsurgically (i.e., antibiotics alone). RESEARCH DESIGN AND METHODS: This was a prospective randomized trial comparing 6- versus 12-week duration of antibiotic treatment. Remission of osteomyelitis during the monitoring period was defined as complete and persistent (>4 weeks) healing of the wound (if present initially), absence of recurrent infection at the initial site or that of adjacent rays, and no need for surgical bone resection or amputation at the end of a follow-up period of at least 12 months after completion of antibiotic treatment. RESULTS: Forty patients followed at five French general hospitals were randomized between January 2007 and January 2009, with 20 treated for 6 weeks and 20 treated for 12 weeks with antibiotics. The two groups were comparable for all variables recorded at inclusion in the study. Remission was obtained in 26 (65%) patients, with no significant differences between patients treated for 6 versus 12 weeks (12/20 vs. 14/20, respectively; P = 0.50). We did not identify any significant parameters associated with patient outcome. Fewer patients treated for 6 weeks experienced gastrointestinal adverse events related to antimicrobial therapy compared with patients treated for 12 weeks (respectively, 15 vs. 45%; P = 0.04). CONCLUSIONS: The present multicenter prospective randomized study provides data suggesting that 6-week duration of antibiotic therapy may be sufficient in patients with DFO for whom nonsurgical treatment is considered.

Outcome of diabetic foot osteomyelitis treated nonsurgically: a retrospective cohort study.

OBJECTIVE: The purpose of this article was to identify criteria predictive of remission in nonsurgical treatment of diabetic foot osteomyelitis. RESEARCH DESIGN AND METHODS: Diabetic patients who were initially treated without orthopedic surgery for osteomyelitis of the toe or metatarsal head of a nonischemic foot between June 2002 and June 2003 in nine French diabetic foot centers were identified, and their medical records were reviewed. Remission was defined as the absence of any sign of infection at the initial or contiguous site assessed at least 1 year after the end of treatment. A total of 24 demographic, clinical, and therapeutic variables including bone versus swab culture-based antibiotic therapy were analyzed. RESULTS: Fifty consecutive patients aged 62.2 +/- 11.1 years (mean +/- SD) with diabetes duration of 16 +/- 10.9 years were included. The mean duration of antibiotic treatment was 11.5 +/- 4.21 weeks. Bone biopsy was routinely available in four of the nine centers. Overall patient management was similar in the different centers except for the use of rifampin, which was recorded more frequently in patients from centers in which a bone biopsy was available. At the end of a 12.8-month posttreatment mean follow-up, 32 patients (64%) were in remission. Bone culture-based antibiotic therapy was the only variable associated with remission, as determined by both univariate (18 of 32 [56.3%] vs. 4 of 18 [22.2%], P = 0.02) and multivariate analyses (odds ratio 4.78 [95% CI 1.0-22.7], P = 0.04). CONCLUSIONS: Bone culture-based antibiotic therapy is a factor predictive of success in diabetic patients treated nonsurgically for osteomyelitis of the foot.

Risk factors for anaemia in patients on prolonged linezolid therapy for chronic osteomyelitis: a case-control study.

OBJECTIVES: The intrinsic properties of the new antibiotic linezolid make it an attractive candidate for the treatment of chronic osteomyelitis. However, data regarding the tolerance of long-term linezolid administration are still lacking. METHODS: The medical charts of patients given linezolid for >4 weeks were retrospectively analysed, especially their haematology. In a case-control study, we compared the respective characteristics of patients who developed anaemia during linezolid therapy and those who did not. RESULTS: Forty-five adults with chronic osteomyelitis received 600 mg linezolid intravenously twice daily for 7 days, and then orally, for a mean total duration of 15.9 weeks (range, 6-36). Anaemia episodes requiring blood transfusion occurred in 13/45 patients (28.9%). Median time from treatment initiation to anaemia onset was 7.4 weeks (range, 4-16). Anaemia was significantly associated with premature linezolid therapy cessation (P = 0.0012). No linezolid-related thrombocytopenia was observed. By univariate analysis, four variables were associated with the occurrence of anaemia: age >58 years, alcohol abuse, diabetes mellitus and low haemoglobin before linezolid treatment. Logistic regression analysis revealed two independent risk factors for anaemia: age >58 years (OR = 20.5, 95% CI 0.69-599; P = 0.0001) and pre-treatment haemoglobin <10.5 g/dL (OR = 16.49, 95% CI 1.06-255; P = 0.04). CONCLUSIONS: Profound anaemia may occur in adult patients with chronic osteomyelitis on prolonged linezolid therapy, and often necessitates linezolid cessation. These patients are likely to be aged >58 years and to have low pre-treatment haemoglobin. The results for the present series might help physicians to identify patients who should not be given long-term linezolid treatment for chronic osteomyelitis.