Emergence and rapid dissemination of highly resistant NDM-14-producing Klebsiella pneumoniae ST147, France, 2022.

BackgroundSince 2021, an emergence of New Delhi metallo-ß-lactamase (NDM)-14-producing Klebsiella pneumoniae has been identified in France. This variant with increased carbapenemase activity was not previously detected in Enterobacterales.AimWe investigated the rapid dissemination of NDM-14 producers among patients in hospitals in France.MethodsAll NDM-14-producing non-duplicate clinical isolates identified in France until June 2022 (n = 37) were analysed by whole genome sequencing. The phylogeny of NDM-14-producers among all K. pneumoniae sequence type (ST) 147 reported in France since 2014 (n = 431) was performed. Antimicrobial susceptibility testing, conjugation experiments, clonal relationship and molecular clock analysis were performed.ResultsThe 37 NDM-14 producers recovered in France until 2022 belonged to K. pneumoniae ST147. The dissemination of NDM-14-producing K. pneumoniae was linked to a single clone, likely imported from Morocco and responsible for several outbreaks in France. The gene bla NDM-14 was harboured on a 54 kilobase non-conjugative IncFIB plasmid that shared high homology with a known bla NDM-1-carrying plasmid. Using Bayesian analysis, we estimated that the NDM-14-producing K. pneumoniae ST147 clone appeared in 2020. The evolutionary rate of this clone was estimated to 5.61 single nucleotide polymorphisms per genome per year. The NDM-14 producers were highly resistant to all antimicrobials tested except to colistin, cefiderocol (minimum inhibitory concentration 2 mg/L) and the combination of aztreonam/avibactam.ConclusionHighly resistant NDM-14 producing K. pneumoniae can rapidly spread in healthcare settings. Surveillance and thorough investigations of hospital outbreaks are critical to evaluate and limit the dissemination of this clone.

Unique clone of Coxiella burnetii causing severe Q fever, French Guiana.

Acute Q fever is an emergent and severe disease in French Guiana. We obtained 5 Coxiella burnetii isolates from samples of patients from Cayenne and found an epidemic clone circulating in Cayenne. This clone has caused pneumonia and endocarditis and seems to be more virulent than previously described strains.

Q fever pneumonia in French Guiana: prevalence, risk factors, and prognostic score.

BACKGROUND: Community-acquired pneumonia (CAP) is the major manifestation of Q fever, an emerging disease in French Guiana. Consequently, the empirical antibiotherapy used for the treatment of CAP combines doxycycline and the recommended amoxicillin. Our objectives were to estimate the prevalence of Q fever pneumonia and to build a prediction rule to identify patients with Q fever pneumonia for empirical antibiotic guidance. METHODS: A retrospective case-control study was conducted on inpatients admitted with CAP in the Department of Infectious Diseases of Cayenne Hospital from 2004 to 2007. Serodiagnosis for Coxiella burnetii was performed for all patients. Risk factor analysis was performed using multivariate logistic regression, and a prognostic score was computed using bootstrap procedures. The score performance characteristics were used to choose the best prediction rule to identify patients with Q fever pneumonia. RESULTS: One hundred thirty-one patients with CAP were included and the Q fever pneumonia prevalence was 24.4% (95% confidence interval [CI], 17.1-31.9). In multivariate analysis, male sex, middle age (age, 30-60 years), headache, leukocyte count <10 × 10(9)/L and C-reactive protein level >185 mg/L were independently associated with Q fever pneumonia. Patients with a predictive score ≤3 had a low risk of Q fever pneumonia with a negative predictive value of 0.97 (95% CI, .90-1) and a sensitivity of 0.97 (95% CI, .89-1). CONCLUSIONS: The prediction rule described here accurately identifies patients with low risk of Q fever pneumonia and may help physicians to make more rational decisions about the empirical use of antibiotherapy. Further prospective studies should be performed to validate this score.

Pneumocystis jiroveci pneumonia revealing de novo mutation causing X-linked hyper-IgM syndrome in an infant male. The first case reported from French Guiana.

BACKGROUND: The X-linked hyper-IgM (XHIM) syndrome is a rare form of primary immunodeficiency disorder characterized by hypogammaglobulinemia and impaired cell immunity. OBSERVATION: We report history of Guianese family affected by XHIM syndrome. The eldest boy died at 7 months from pneumonia. The 5-month-old youngest boy presented with a potentially fatal episode of Pneumocystis jiroveci pneumonia. The diagnosis was done in the Pediatric Unit of Immunohematology of Hopital Necker in Paris. CONCLUSIONS: This report points to the importance of diagnosis of XHIM to allow early treatment to minimize serious infections and to detect carriers in XHIM families for genetic counseling.

Impact of vaccination on the symptoms of hospitalised patients with SARS-CoV-2 Delta variant (B.1.617.1) infection.

OBJECTIVES: The diffusion of the SARS-CoV-2 Delta (B.1.617.2) variant and the waning of immune response after primary Covid-19 vaccination favoured the breakthrough SARS-CoV-2 infections in vaccinated subjects. To assess the impact of vaccination, we determined the severity of infection in hospitalised patients according to vaccine status. METHODS: We performed a retrospective observational study on patients hospitalised in 10 centres with a SARS-CoV-2 infection (Delta variant) from July to November 2021 by including all patients who had completed their primary vaccination at least 14 days before hospital admission and the same number of completely unvaccinated patients. We assessed the impact of vaccination and other risk factors through logistic regression. RESULTS: We included 955 patients (474 vaccinated and 481 unvaccinated). Vaccinated patients were significantly older (75.0 [63.25-84.0] vs. 55.0 [38.0-73.0]; p < 0.001), more frequently males (55.1% (261/474) vs. 46.4% (223/481); p = 0.009), and had more comorbidities (2.0 [1.0-3.0] vs. 1.0 [0.0-2.0]; p < 0.001). Vaccinated patients were less often admitted for Covid-19 (59.3% (281/474) vs. 75.1% (361/481); p < 0.001), had less extended lung lesions (≤25%: 64.3% (117/182) vs. 38.4% (88/229); p < 0.001), required oxygen less frequently (57.5% (229/398) vs. 73.0% (270/370); p < 0.001), at a lower flow (3.0 [0.0-8.7] vs. 6.0 [2.0-50.0] L/min, p < 0.001), and for a shorter duration (3 [0.0-8.0] vs. 6 [2.0-12.0] days, p < 0.001)., and required less frequently intensive care unit admission (16.2% (60/370) vs. 36.0% (133/369); p < 0.001) but had comparable mortality in bivariate analysis (16.7% (74/443) vs. 12.2% (53/433); p = 0.075). Multivariate logistic regression showed that vaccination significantly decreased the risk of death (0.38 [0.20-0.70](p = 0.002), ICU admission (0.31 [0.21-0.47](p < 0.001) and oxygen requirement (0.16 [0.10-0.26](p < 0.001), even among older patients or with comorbidities. CONCLUSIONS: Among patients hospitalised with a delta variant SARS-CoV-2 infection, vaccination was associated with less severe forms, even in the presence of comorbidities.

Q Fever as a Cause of Community-Acquired Pneumonia in French Guiana.

In French Guiana, community-acquired pneumonia (CAP) represents over 90% of Coxiella burnetii acute infections. Between 2004 and 2007, we reported that C. burnetii was responsible for 24.4% of the 131 CAP hospitalized in Cayenne. The main objective of the present study was to determine whether the prevalence of Q fever pneumonia remained at such high levels. The secondary objectives were to identify new clinical characteristics and risk factors for C. burnetii pneumonia. A retrospective case-control study was conducted on patients admitted in Cayenne Hospital, between 2009 and 2012. All patients with CAP were included. The diagnosis of acute Q fever relied on titers of phase II IgG ≥ 200 and/or IgM ≥ 50 or seroconversion between two serum samples. Patients with Q fever were compared with patients with non-C. burnetii CAP in bivariate and multivariate analyses. During the 5-year study, 275 patients with CAP were included. The etiology of CAP was identified in 54% of the patients. C. burnetii represented 38.5% (106/275; 95% CI: 31.2-45.9%). In multivariate analysis, living in Cayenne area, being aged 30-60 years, C-reactive protein (CRP) > 185 mg/L, and leukocyte count < 10 G/L were independently associated with Q fever. The prevalence of Q fever among CAP increased to 38.5%. This is the highest prevalence ever reported in the world. This high prevalence justifies the systematic use of doxycycline in addition to antipneumococcal antibiotic regimens.

A comparison of the pharmacodynamics and pharmacokinetics of bupivacaine, ropivacaine (with epinephrine) and their equal volume mixtures with lidocaine used for femoral and sciatic nerve blocks: a double-blind randomized study.

BACKGROUND: Mixtures of lidocaine with a long-acting local anesthetic are commonly used for peripheral nerve block. Few data are available regarding the safety, efficacy, or pharmacokinetics of mixtures of local anesthetics. In the current study, we compared the effects of bupivacaine 0.5% or ropivacaine 0.75% alone or in a mixed solution of equal volumes of bupivacaine 0.5% and lidocaine 2% or ropivacaine 0.75% and lidocaine 2% for surgery after femoral-sciatic peripheral nerve block. The primary end point was onset time. METHODS: In a double-blind, randomized study, 82 adults scheduled for lower limb surgery received a sciatic (20 mL) and femoral (20 mL) peripheral nerve block with 0.5% bupivacaine (200 mg), a mixture of 0.5% bupivacaine 20 mL (100 mg) with 2% lidocaine (400 mg), 0.75% ropivacaine (300 mg) or a mixture of 0.75% ropivacaine 20 mL (150 mg) with 2% lidocaine (400 mg). Each solution contained epinephrine 1:200,000. Times to perform blocks, onset times (end of injection to complete sensory and motor block), duration of sensory and motor block, and morphine consumption via IV patient-controlled analgesia were compared. Venous blood samples of 5 mL were collected for determination of drug concentration at 0, 5, 15, 30, 45, 60, and 90 min after placement of the block. RESULTS: Patient demographics and surgical times were similar for all four groups. Sciatic onset times (sensory and motor block) were reduced by combining lidocaine with the long-acting local anesthetic. The onset of bupivacaine-lidocaine was 16 +/- 9 min versus 28 +/- 12 min for bupivacaine alone. The onset of ropivacaine-lidocaine was 16 +/- 12 min versus 23 +/- 12 for ropivacaine alone. Sensory blocks were complete for all patients within 40 min for those receiving bupivacaine-lidocaine versus 60 min for those receiving bupivacaine alone and 30 min for those receiving ropivacaine-lidocaine versus 40 min for those receiving ropivacaine alone (P < 0.05). Duration of sensory and motor block was significantly shorter in mixture groups. There was no difference among groups for visual analog scale pain scores and morphine consumption during the 48 h postoperative period, except for bupivacaine alone (median: 9 mg) versus bupivacaine-lidocaine mixture (15 mg), P < 0.01. There was no difference in the incidence of adverse events among groups. Plasma concentrations of bupivacaine and ropivacaine were higher, and remained elevated longer, in patients who received only the long-acting local anesthetic compared to patients who received the mixture of long-acting local anesthetic with lidocaine (P < 0.01). CONCLUSION: Mixtures of long-acting local anesthetics with lidocaine induced faster onset blocks of decreased duration. Whether there is a safety benefit is unclear, as the benefit of a decreased concentration of long-acting local anesthetic may be offset by the presence of a significant plasma concentration of lidocaine.

Maintaining antiretroviral therapy reduces the risk of AIDS-defining events in patients with uncontrolled viral replication and profound immunodeficiency.

BACKGROUND: The benefits of continuing antiretroviral therapy are questionable in human immunodeficiency virus (HIV) type 1-infected patients with profound immunodeficiency and multiple treatment failure due to viral resistance. METHODS: From the French Hospital Database on HIV, we selected 12,765 patients with a CD4(+) cell count <200 cells/mm(3) who received a combination antiretroviral therapy (cART) during 2000-2005. Three groups of patients were defined: patients who interrupted cART at least once, patients who had at least 2 consecutive detectable viral loads (VLs) while receiving cART, and patients who had undetectable VL during treatment with cART. Incidence rates and risks of new acquired immunodeficiency syndrome-defining events (ADEs) were assessed among the 3 groups of patients, overall and after CD4(+) cell count stratification (<50 and 50-200 cells/mm(3)). RESULTS: The estimated incidence rates +/- standard deviation of ADEs were 18.5+/-1.9, 14.5+/-0.7, and 4.9+/-0.5, respectively, for patients who interrupted cART, patients who had detectable VL during treatment with cART, and patients who had undetectable VL during treatment with cART. These differences were observed in both CD4(+) cell count strata. Overall, after adjustment, risks of a new ADE in patients who had detectable VL and in patients who had undetectable VL while receiving cART were 22% and 62% lower, respectively, than in patients who stopped cART. Among patients with CD4(+) cell count <50 cells/mm(3), the risk of a new ADE was 22% lower in patients who continued to receive a failing cART regimen than in patients who stopped treatment with cART. Likewise, among patients with a CD4(+) cell count of 50-200 cells/mm(3), the risk was 34% lower in patients who continued to receive a failing cART regimen than in those who stopped taking cART. CONCLUSIONS: Even when effective virological control is no longer achievable, cART still reduces the risk of ADEs in profoundly immunodeficient HIV-infected patients.

Q fever epidemic in Cayenne, French Guiana, epidemiologically linked to three-toed sloth.

A Q fever epidemic occurred in 2013 in a small military residential area in Cayenne, French Guiana. A retrospective cohort study was conducted to identify Q fever risk factors. Confirmed acute Q fever case was defined as positive serology (IgM ≥ 50 and phase II IgG ≥ 200) and/or positive qPCR on serum or blood. In addition, wild mammals were captured at the study site and tested by serology and real-time PCR performed on blood, vaginal swabs and ticks. The attack rate was 20 percent (11/54). All the cases were symptomatic with fever >38.5 °C and community-acquired pneumonia for four cases. Log binomial multivariate models identified two independent risk factors associated with Q fever: to clean the house (RRa = 7.5 CI95% [1.03-55.3]) and to carry a three-toed sloth in arms (RRa = 2.6 CI95% [1.1-5.8]). Eighteen marsupial individuals were captured, all PCRs were negative but 17% (3/18) had a positive serology. Another study conducted after the epidemic found only one (1/4) three-tooth sloth (Bradypus tridactylus) with feces highly infectious for C. burnetii MST17. The same strain C. burnetii genotype 17 has been laboratory- confirmed in this mammal and in human cases. These results support the implication of three-toed-sloth in this epidemic. Human contamination mainly occurs through inhalation of infectious aerosols as suggested by high relative risk associated with house cleaning activities and pulmonary forms of the disease, and through direct contact with three- toed-sloth. Positive serological results among marsupials confirm wildlife exposure and suggest a more complex sylvatic transmission cycle among wild mammals.

Influence of geographic origin on AIDS and serious non-AIDS morbidity/mortality during cART among heterosexual HIV-infected men and women in France.

BACKGROUND: The influence of geographic origin on the risk of severe illness and death on cART has not been explored in European countries. METHOD: We studied antiretroviral-naïve heterosexual HIV-1-infected individuals enrolled in the FHDH-ANRS CO4 cohort in France who started cART between 2006 and 2011. Individuals originating from France (French natives), sub-Saharan Africa (SSA) and non-French West-Indies (NFW) were studied until 2012. Crude and adjusted rate ratios (aRR) of severe morbid events/deaths (AIDS-related and non-AIDS-related) were calculated using Poisson regression models stratified by sex, comparing each group of migrants to French natives. RESULTS: Among 2334 eligible men, 1379 (59.1%) originated from France, 838 (35.9%) from SSA and 117 (5.0%) from NFW. SSA male migrants had a higher aRR for non-AIDS infections, particularly bacterial infections (aRR 1.56 (95% CI 1.07-2.29), p = 0.0477), than French natives. Among 2596 eligible women, 1347 (51.9%) originated from France, 1131 (43.6%) from SSA, and 118 (4.5%) from NFW. SSA and NFW female migrants had a higher aRR for non-AIDS infections, particularly non-bacterial infections (respectively, 2.04 (1.18-3.53) and 7.87 (2.54-24.4), p = 0.0010), than French natives. We observed no other significant differences related to geographic origin as concerns the aRRs for AIDS-related infections or malignancies, or for other non-AIDS events/deaths such as cardiovascular disease, neurological/psychiatric disorders, non-AIDS malignancies and iatrogenic disorders, in either gender. CONCLUSION: Heterosexual migrants from SSA or NFW living in France have a higher risk of non-AIDS-defining infections than their French native counterparts. Special efforts are needed to prevent infectious diseases among HIV-infected migrants.

Increased incidence of cutaneous mycoses after HAART initiation: a benign form of immune reconstitution disease?

Immune reconstitution disease (IRD) has been associated with many pathogens after the initiation of antiretroviral therapy for advanced HIV infection. A retrospective cohort study was conducted to determine whether cutaneous mycoses were also associated with IRD. After adjusting for various confounding factors, the recent initiation of HAART was found to be associated with an increased incidence of cutaneous mycoses when compared with untreated patients.

Salmonella enterica serovar Panama meningitis in exclusive breastfeeding infants: Report of 4 cases, clinical features and therapeutic challenges.

RATIONALE: The pathway of Nontyphoid Salmonella meningitis, especially in exclusive breastfeeding infants, has not been well characterized. PATIENT CONCERNS: We analyzed data related to nontyphoid Salmonella meningitis in 4 infants. DIAGNOSES: No diarrhea was observed and the coproculture was negative for all patients. INTERVENTIONS: Early diagnosis and treatment with combination of third-generation cephalosporins plus quinolones for a minimum of 3 weeks is necessary to avoid severe sequelae and death. OUTCOMES: The first 3 patients had a good evolution, whereas the last patient had multiple brain abscesses and hydrocephalus requiring treatment with a ventriculoperitoneal shunt. LESSONS: The highlights of our study are that all infants were exclusively breastfed, no diarrhea observed and the negative coproculture for all the 4 patients, which is relatively rare for Salmonella infection.

A comparison of mepivacaine versus lidocaine for episcleral (sub-tenon's) block for cataract surgery in an ambulatory setting.

BACKGROUND AND OBJECTIVES: For eye surgery, motor block is still often requested by the surgeon. For cataract surgery, rapid block resolution allows eyelids to move and allows eye-patch removal. Therefore, short-duration block is useful in early rehabilitation for ambulatory surgery. Lidocaine is classically assumed to have shorter duration than mepivacaine. Therefore, lidocaine alone might be considered as an alternative to mepivacaine. METHODS: In this randomized, double-blind study, we compared mepivacaine 2% (n = 22) and lidocaine 2% (n = 25) in 47 patients who received episcleral (sub-Tenon's) block for cataract surgery. Akinesia score was measured 1, 5, 10, and 15 minutes and 1, 2, 4, and 6 hours after the end of injection. Primary outcome was block duration (time from injection to full recovery). Secondary outcomes were time to block onset and best akinesia score for each patient. Complications were recorded. RESULTS: The 2 groups were similar for demographic and anesthetic features. We observed no significant difference between mepivacaine and lidocaine in terms of onset, quality of akinesia, and block duration. One case of ocular hypertonia and 1 case of strabismus were observed in the lidocaine group, which could be imputed to hyaluronidase unavailability during the study period or to increased lidocaine myotoxicity. CONCLUSIONS: We found no argument to favor lidocaine over mepivacaine in episcleral (sub-Tenon's) eye block, especially in terms of motor-block duration.

Clinical epidemiology and resistance mechanisms of carbapenem-resistant Acinetobacter baumannii, French Guiana, 2008-2014.

This study investigated the clinical epidemiology and resistance mechanisms of Acinetobacter baumannii and characterised the clonal diversity of carbapenem-resistant A. baumannii (CRAB) during an ICU-associated outbreak at Cayenne Hospital, French Guiana. All non-duplicate A. baumannii isolates from 2008 to 2014 were tested for antibiotic susceptibility by disk diffusion. Multilocus sequence typing, pulsed-field gel electrophoresis (PFGE) and characterisation of carbapenemase-encoding genes were performed on CRAB. Of the 441 A. baumannii isolates, most were from males (54.0%) and were detected mainly from the ICU (30.8%) and medicine wards (21.8%). In the ICU, strains were mainly isolated from the respiratory tract (44.1%) and bloodstream (14.0%), whereas in medicine wards they mainly were from wound/drainage (36.5%) and bloodstream (25.0%). A. baumannii showed the greatest susceptibility to piperacillin/tazobactam (92.7%), imipenem (92.5%), colistin (95.6%) and amikacin (97.2%), being lower in the ICU and medicine wards compared with other wards. An outbreak of OXA-23-producing CRAB occurred in the 13-bed ICU in 2010. CRAB strains were more co-resistant to other antimicrobials compared with non-CRAB. Molecular genetics analysis revealed five sequence types [ST78, ST107 and ST642 and two new STs (ST830 and ST831)]. Analysis of PFGE profiles indicated cross-transmissions of CRAB within the ICU, between the ICU and one medicine ward during transfer of patients, and within that medicine ward. This study provides the first clinical and molecular data of A. baumannii from French Guiana and the Amazon basin. The ICU was the highest risk unit of this nosocomial outbreak of OXA-23-producing CRAB, which could subsequently disseminate within the hospital.

A predictive score for hypotension in patients with confirmed dengue fever in Cayenne Hospital, French Guiana.

Background: Identifying patients at risk of developing severe dengue is challenging. The objective of the present study was to determine the incidence of hypotension and its predictive factors during the Dengue 2 epidemic in 2013. Methods: In 2013, a longitudinal study was performed using data from all confirmed cases of dengue seen in Cayenne General Hospital. The analysis used Cox proportional modeling to obtain adjusted hazards ratios for hypotension. Results: A total of 806 confirmed patients were included 78 (9.6%) of whom developed hypotension. Extensive purpura, cutaneomucous hemorrhage, serous effusion and age 1-15 years were associated with subsequent hypotension whereas 'aches' and a rash were associated with a lower incidence of hypotension. The biological variables independently associated with hypotension were: increase of hematocrit, low protein concentrations, low sodium concentration and lymphocytes over 1400/ml. A risk score was computed from the scaled Cox model coefficient. Conclusions: From a clinician's perspective, extensive purpura, cutaneomucous hemorrhage, serous effusion, age 1-15 years, hematocrit increase, low protein, low sodium, lymphocytosis and the absence of aches or of a rash, may be important warning signs to predict subsequent hypotension and shock. Over half of the patients with the highest risk score subsequently developed hypotension. The prognostic score had a 48.2% sensitivity with less than 10% of false positives. This score requires external validation before its impact on clinical practice is evaluated.

Influence of geographic origin, sex, and HIV transmission group on the outcome of first-line combined antiretroviral therapy in France.

BACKGROUND: More data are needed on the influence of geographic origin, sex, and the HIV transmission group on biological and clinical outcomes after first-line combined antiretroviral therapy (cART) initiation. METHODS: We studied antiretroviral-naive HIV-1-infected adults enrolled in the French Hospital Database on HIV cohort in France and who started cART between 2006 and 2011. The censoring date of the study was 31 December 2012. According to geographic origin [French natives (FRA) or sub-Saharan Africa/non-French West Indies (SSA/NFW)], sex, and HIV transmission group, we assessed 2-year Kaplan-Meier probabilities and adjusted hazard ratios (aHRs) for plasma viral load undetectability and CD4 cell recovery, and 5-year cumulative incidences and aHRs for negative clinical outcomes (AIDS-defining event, serious non-AIDS events, or death). RESULTS: Of 9746 eligible individuals, 7297 (74.9%) were FRA and 2449 (25.1%) were sub-Saharan Africa/non-French West Indies migrants. More migrants (38.1%) than nonmigrants (27.5%) started cART with a CD4 cell count less than 200/µl (P < 0.0001). By comparison with FRA MSM, nonhomosexual men, whatever their geographic origin, had lower aHRs for viral undetectability; all patient groups, particularly migrants, had lower aHRs for CD4 cell recovery than FRA MSM; aHRs for negative clinical outcome (360 new AIDS-defining events, 1376 serious non-AIDS events, 38 deaths) were also higher in nonhomosexual men, regardless of geographic origin. Preexisting AIDS status, a lower CD4 cell count and older age at cART initiation had the biggest impact on changes between the crude and aHRs of clinical outcomes. CONCLUSION: Compared with FRA MSM, all migrants had a lower likelihood of CD4 cell recovery, and nonhomosexual men had a higher likelihood of negative virological and clinical outcomes.

Rainfall and sloth births in may, Q fever in July, Cayenne, French Guiana.

Q fever in French Guiana is correlated with the rainy season. We found a 1- to 2-month lagged correlation between Q fever incidence and the number of births of three-toed sloth. This result strengthens the hypothesis that the three-toed sloth is the wild reservoir of Q fever in French Guiana.

Later cART initiation in migrant men from sub-Saharan Africa without advanced HIV disease in France.

OBJECTIVE: To compare the time from entry into care for HIV infection until combination antiretroviral therapy (cART) initiation between migrants and non migrants in France, excluding late access to care. METHODS: Antiretroviral-naïve HIV-1-infected individuals newly enrolled in the FHDH cohort between 2002-2010, with CD4 cell counts >200/µL and no previous or current AIDS events were included. In three baseline CD4 cell count strata (200-349, 350-499, ≥ 500/µL), we examined the crude time until cART initiation within three years after enrollment according to geographic origin, and multivariable hazard ratios according to geographic origin, gender and HIV-transmission group, with adjustment for baseline age, enrollment period, region of care, plasma viral load, and HBV/HBC coinfection. RESULTS: Among 13338 individuals, 9605 (72.1%) were French natives (FRA), 2873 (21.4%) were migrants from sub-Saharan Africa/non-French West Indies (SSA/NFW), and 860 (6.5%) were migrants from other countries. Kaplan-Meier probabilities of cART initiation were significantly lower in SSA/NFW than in FRA individuals throughout the study period, regardless of the baseline CD4 stratum. After adjustment, the likelihood of cART initiation was respectively 15% (95%CI, 1-28) and 20% (95%CI, 2-38) lower in SSA/NFW men than in FRA men who had sex with men (MSM) in the 350-499 and ≥ 500 CD4 strata, while no difference was observed between other migrant groups and FRA MSM. CONCLUSION: SSA/NFW migrant men living in France with CD4 >350/µL at entry into care are more likely to begin cART later than FRA MSM, despite free access to treatment. Administrative delays in obtaining healthcare coverage do not appear to be responsible.

Immunologic and clinical responses to highly active antiretroviral therapy over 50 years of age. Results from the French Hospital Database on HIV.

OBJECTIVE: To study immunologic and clinical responses to HAART in patients over 50 years old. DESIGN AND METHODS: A prospective cohort study which included 68 hospitals in France. A total of 3015 antiretroviral-naive patients, 401 of whom were aged 50 years or over, were enrolled following initiation of HAART. The influence of age on the mean CD4 cell count increase on HAART was studied by using a two-slope mixed model. Progression, defined by the occurrence of a new AIDS-defining event (ADE) or death, was studied by Cox multivariate analyses. RESULTS: Among patients with baseline HIV RNA above 5 log copies/ml, CD4 mean increase during the first 6 months on HAART was +42.9 x 10(6) cells/l per month in patients under 50 years and +36.9 x 10(6) cells/l per month in patients over 50 years (P < 0.0001); subsequently, the respective monthly changes were +17.9 and +15.6 x 10(6) cells/l per month (P < 0.0001). Similar trends were observed in patients with baseline HIV RNA below 5 log copies/ml, and also after stratification for the baseline CD4 cell count. After a median follow-up of 31.5 months, 263 patients had a new ADE and 44 patients died. After adjustment for baseline characteristics, older patients had a significantly higher risk of clinical progression (hazard ratio (HR) = 1.52 [95% confidence interval (CI), 1.15-2.00]) and were more likely to achieve a viral load below 500 copies/ml [HR = 1.23, (95% CI, 1.11-1.38)]. CONCLUSION: Patients over 50 years of age have an immunologic response to HAART. However, their CD4 cell reconstitution is significantly slower than in younger patients, despite a better virologic response. This impaired immunologic response may explain their higher risk of clinical progression.