Dramatic decline in new HIV diagnoses in persons born in France in a large nationwide HIV cohort.

OBJECTIVES: As trends in new HIV diagnoses represent a measure of the HIV epidemic, we conducted a 6-year longitudinal study to evaluate the change in rates of new HIV diagnosis, stratified by birthplace, HIV risk groups and CD4 cell count at diagnosis in a large French multicentre cohort. STUDY DESIGN: We performed a retrospective cohort study using data from the mainland French Dat'AIDS cohort. METHODS: Data were obtained for subjects with a new HIV diagnosis date between 2013 and 2018. HIV diagnosis date was defined as the date of the first known positive HIV serology. RESULTS: Between 2013 and 2018, a total of 68,376 people living with HIV (PLHIV) were followed in the Dat'AIDS cohort; 9543 persons were newly diagnosed with HIV. The annual number of new HIV diagnoses decreased from 1856 in 2013, to 1149 in 2018 (-38.1%), P = 0.01; it was more pronounced among subjects born in France, from 858 to 484 (-43.6%), P < 0.01, than in those born abroad (-23.8%, from 821 to 626, P = 0.13). Among subjects born in France, the decrease over the period was -46.7% among men who have sex with men (MSM), -43.5% for heterosexual women and -33.3% for heterosexual men. CONCLUSION: Our findings show changes in HIV epidemiology in PLHIV born in France, with a decline around 40% in new HIV diagnoses, and a more pronounced decrease among MSM and heterosexual women. Our results support the long-term effectiveness of the antiretroviral therapy as a prevention strategy among the various tools for HIV prevention.

Post-exposure prophylaxis completion and condom use in the context of potential sexual exposure to HIV.

OBJECTIVES: Post-exposure prophylaxis (PEP) care remains a challenge for individuals with potential sexual exposure to HIV in terms of PEP completion and ongoing risk behaviours. METHODS: A retrospective analysis was carried out on data from the French Dat'AIDS prevention cohort (NCT03795376) for individuals evaluated for PEP between 2004 and 2017. A multivariable analysis was performed of predictors of both PEP completion and condom use [odds ratios (ORs)] and their associated probabilities (P, with P > 95% being clinically relevant). RESULTS: Overall, 29 060 sexual exposures to HIV were evaluated for PEP [36% in men who have sex with men (MSM) and 64% in heterosexuals]. Overall, 12 different PEP regimens were offered in 19 240 cases (46%). Tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) was the preferred backbone (n = 14 304; 74%). We observed a shift from boosted protease inhibitor-based regimens to nonnucleoside reverse transcriptase inhibitor- or integrase inhibitor-based regimens in recent years. Overall, 20% of PEP prescriptions were prematurely discontinued. Older age, MSM, intercourse with a sex worker, rape and intercourse with a known HIV-infected source patient were factors associated with increased rates of PEP completion (OR > 1; P > 98%). None of the 12 PEP regimens was associated with premature discontinuation. We also found 12 774 cases of unprotected sexual intercourse (48%). Condom use decreased (OR < 1; P > 99%) with the year of exposure, and was lower in MSM and rape victims. Condom use increased (OR > 1, P > 99%) with age, and was higher in those who had intercourse with a sex worker or with a female partner and in those with knowledge of the partner's HIV status. CONCLUSIONS: We provide new insights into how rates of condom use and PEP completion might be improved in those receiving PEP by targeting certain groups of individuals for interventions. In particular, youth and MSM at risk should be linked in a prevention-to-care continuum.

Too fast to stay on track? Shorter time to first anti-retroviral regimen is not associated with better retention in care in the French Dat'AIDS cohort.

BACKGROUND: Rapid antiretroviral therapy (ART) initiation has been proven beneficial for patients and the community. We aimed to analyze recent changes in timing of ART initiation in France and consequences of early start. METHODS: We selected from a prospective nationwide cohort, on 12/31/2017, patients with HIV-1 infection diagnosed between 01/01/2010 and 12/31/2015. We described time from (1) diagnosis to first specialized medical encounter, (2) from this encounter to ART initiation, (3) from diagnosis to first undetectable HIV viral load (VL). We analyzed the determinants of measured temporal trends. A multivariate logistic regression was performed to assess characteristics related with 1-year retention in care. RESULTS: In the 7 245 included patients, median time (1) from HIV diagnosis to first medical encounter was 13 (IQR: 6-32) days, (2) to ART initiation was 27 (IQR: 9-91) days, decreasing from 42 (IQR: 13-272) days in 2010 to 18 (IQR: 7-42) in 2015 (p<0.0001), (3) to first undetectable VL was 257 (IQR: 151-496) days, decreasing from 378 (IQR: 201-810) days in 2010 to 169 (IQR: 97-281) in 2015. After one year, proportion of patients alive and still in care was significantly lower in those in the lower quartile of time from first encounter to ART (<9 days) than those in the higher quartile (>90 days), 79.9% and 85.2%, respectively (p<0.0001). CONCLUSIONS: In a country with unrestricted rapid access to ART, keeping recently diagnosed HIV infected patients in care remains challenging. Starting ART rapidly did not seem to be profitable for all and every patient.

First year of pre-exposure prophylaxis implementation in France with daily or on-demand tenofovir disoproxil fumarate/emtricitabine.

BACKGROUND: In January 2016, the French Medicine Agency initiated a Temporary Recommendation for Use (TRU) to allow the use of oral intake of tenofovir disoproxil fumarate and emtricitabine for pre-exposure prophylaxis (PrEP) in adults at high risk of HIV. We report the results of the first year of PrEP implementation in France. METHODS: Data were collected by physicians using a secured web subject-monitoring interface, with two forms: an initiation form, with patients' baseline characteristics, and an HIV seroconversion form. Univariate and adjusted multivariate analysis using a logistic regression model were performed to identify baseline factors associated with on-demand PrEP regimen prescription. RESULTS: From 4 January 2016 to 28 February 2017, 3405 subjects were enrolled, with 2774 initiation forms completed; 98.1% were male and 96.9% were MSM. An on-demand regimen was prescribed to 57% of subjects. Older age (OR for participants older than 50 years = 1.76, 95% CI 1.35-2.3, P < 0.001) and site of prescription (OR of former IPERGAY sites = 2.28, 95% CI 1.84-2.83, P < 0.001) were associated with on-demand prescription. Those reporting sexually transmitted infection (STI) and condomless anal sex with at least two different partners were less likely to receive on-demand PrEP (OR = 0.68, 95% CI 0.57-0.82 and 0.75, 95% CI 0.57-0.98, respectively; P < 0.05 for all). Four breakthrough HIV infections were reported during the study, in the context of PrEP interruption or acute infection at the time of PrEP initiation. CONCLUSIONS: In a real-life setting in France, PrEP was used, either daily or on-demand, mostly by MSM, with breakthrough infections being rare.

Missed opportunities of HIV pre-exposure prophylaxis in France: a retrospective analysis in the French DAT'AIDS cohort.

BACKGROUND: HIV pre-exposure prophylaxis (PrEP) was implemented in France in November 2015 based on individual-level risk factors for HIV infection. We evaluated the proportion of missed opportunities for PrEP among newly HIV-diagnosed people entering the Dat'AIDS cohort in 2016. METHODS: Multicenter retrospective analysis in 15 French HIV clinical centers of patients with a new diagnosis of HIV infection. Among them we differentiated patients according to the estimated date of infection: those occurring in the PrEP area (a previous negative HIV test in the last 12 months or those with an incomplete HIV-1 western blot (WB) with no HIV-1 anti-Pol-antibody at time of HIV diagnosis) and those in the pre-PrEP area (older infections). Epidemiological, biological and clinical data at HIV diagnosis were collected. Clinicians retrospectively identified potential eligibility for PrEP based on individual-level risk factors for HIV infection among those infected in the PrEP area. RESULTS: Among 966 patients with a new HIV diagnosis, 225 (23.3%) were infected in the PrEP area and 121 (53.8%) had complete data allowing evaluation of PrEP eligibility. Among them, 110 (91%) would have been eligible for PrEP, median age 31 years, with 68 (75.6%) born in France and 10 (11.1%) in Central/West Africa, with more than one previous STI in 19 (15.7%). The main eligibility criteria for PrEP were being a man who had sex with men or transgender 91 (82.7%) with at least one of the following criteria: unprotected anal sex with ≥2 partners in the last 6 months: 67 (60.9%); bacterial sexually transmitted infection in the last 12 months: 33 (30%); Use of psychoactive substances in a sexual context (chemsex): 16 (14.5%). PrEP was indicated for other HIV risk factors in 25 (22.7%). CONCLUSION: With 91% (110/121) of patients infected in the PrEP area eligible for PrEP, this study highlights the high potential of PrEP in avoiding new infection in France but also shows a persistent delay in HIV testing. Thus, an important limit on PrEP implementation in France could be insufficient screening and care access.

Satisfaction with sexual life in people living with HIV/AIDS: the persistent weight of the fear of transmission.

Sexual life is an important dimension of quality of life, which may be affected by the fear of transmission in people living with HIV/AIDS (PLWHA), despite the fact that antiretroviral therapy prevents person-to-person transmission. We, therefore, aimed to explore the sexual life satisfaction of PLWHA and its correlation with their fear of HIV transmission and self-esteem. Consecutive adult PLWHA from seven HIV care facilities in the Rhone-Alpes region, France, were asked to complete a self-administered, anonymous questionnaire concerning sociological and medical data, satisfaction with sexual life (18 questions), and self-esteem (Rosenberg score). Overall, 690 PLWHA answered the questionnaire (mean age 49.2 ± 11 years); 74.9% were men, of which 75.1% had sex with men. Overall, 68.0% of respondents feared transmitting HIV (a lot/a bit). A lower satisfaction with sexual life was significantly associated with being female, not having a stable sexual partner, being unemployed, having a low income, experiencing a fear of HIV transmission, having lower self-esteem, and not reporting an excellent/very good health status. These results strongly suggest that the information concerning the antiretroviral-induced suppression of infectivity should be widely diffused, as this may enhance the quality of sexual life in PLWHA.

Which antiretrovirals should be prescribed as first-line treatments? Changes over the past 10 years in France.

OBJECTIVE: To describe the changes in first-line antiretroviral (ART) regimens in France between 2005 and 2015 and patients' characteristics related to the use of protease inhibitors in 2015. METHODS: We extracted all patients starting ART between 2005 and 2015 from a large prospective cohort. Regimens were classified as three nucleoside reverse transcriptase inhibitors (NRTI), or two NRTIs with a boosted protease inhibitor (bPI), with a non-nucleoside reverse transcriptase inhibitor (NNRTI), or with an INSTI. Patients' characteristics at the time of initiation were collected. A multinomial logit model was fitted to analyze characteristics related to the choice of regimen in 2015. RESULTS: We analyzed data from 15,897 patients. The proportion of patients starting with (i) a bPI decreased from 60% before 2014 to 38.1% in 2015; (ii) an NNRTI decreased from 30% to 17.8% in 2015; (iii) an INSTI gradually increased to 39.4% in 2015. In 2015, patients with an initial viral load ˃5 log copies/mL were less likely to receive NNRTI (OR=0.08) or INSTI regimens (OR=0.69) than bPIs. Patients with initial CD4+ T cell count ˂200/mm3 were less likely to receive an NNRTI (OR=0.28) or an INSTI regimen (OR=0.52) than a bPI. Women were less likely to receive an NNRTI (OR=0.79) or an INSTI regimen (OR=0.71) than a bPI; although this depended on age. CONCLUSION: The use of bPI as first-line ART declined sharply in France from 2005 to 2015. bPI remained of preferential use in patients with high viral load, low CD4+ T cell count, and in women.

Risk of diabetes in HIV-infected patients is associated with cirrhosis but not with chronic HCV coinfection in a French nationwide HIV cohort.

BACKGROUND: Both human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections have been reportedly associated with a higher risk of diabetes mellitus (DM) but results are conflicting. AIMS: To determine whether there is an association between chronic HCV and the incidence of DM, and to study the role of factors such as cirrhosis, IFN-based HCV therapy, sustained virologic response (SVR) and chronic HBV infection among patients living with HIV (PLHIV) followed in a large French multicentre cohort in the combination antiretroviral therapy (cART) era. METHODS: All PLHIV followed up in the Dat'AIDS cohort were eligible. Cox models for survival analysis were used to study the time to occurrence of DM. RESULTS: Among 28 699 PLHIV, 4004 patients had chronic HCV infection. The mean duration of HCV follow-up was 12.5 ± 8.1 years. The rate ratio of DM was 2.74 per 1000 person-years. By multivariate analysis, increasing age, body mass index>25, AIDS status, nadir CD4 cell count ≤200/mm3 , detectable HIV viral load and cirrhosis (HR 2.26 95% CI 1.14-1.18; P < 0.0001) were predictors of DM, whereas longer cART duration was associated with a lower risk of DM. Chronic HCV and HBV infection and IFN-based HCV therapy were not associated with DM. In a subanalysis among HCV-infected patients, SVR was not related to DM. CONCLUSIONS: Our study shows that in the HIV population, cirrhosis is associated with an increased occurrence of DM, but not chronic HCV infection or duration of HCV infection.

No relationship between late HIV diagnosis and social deprivation in newly diagnosed patients in France.

OBJECTIVES: The aim of the study was to determine whether there is a relationship between social deprivation and time of HIV diagnosis in France. METHODS: Prospectively collected data from a multicentre database were used in the study. Patients with a first HIV diagnosis between 1 January 2014 and 31 December 2015 were selected from the database. Deprivation was measured using the European Deprivation Index (EDI), which is an ecological index constructed from the address of residence and based on the smallest geographical census unit, in which individuals are classified so as to be comparable with national quintiles. Time of diagnosis was classified as being at an early, intermediate, late, or advanced stage of disease. Age, gender, distance from home to HIV centre, most probable route of infection, and hepatitis B or C coinfection were considered in the analysis. Because of a strong interaction between gender and most probable route of infection, we constructed a 'population' variable: men who have sex with men (MSM), heterosexual men and women. RESULTS: Of 1421 newly diagnosed patients, 44% were diagnosed either late or at an advanced stage of disease, and 46.3% were in the highest deprivation quintile. Using multivariate logistic regression, 'population' [odds ratio (OR) 0.62 (95% confidence interval (CI) 0.48-0.78) for MSM compared with women] and age [OR 1.39 (95% CI 1.07-1.80), 1.72 (1.32-2.23) and 1.86 (1.40-2.47) for the second, third and fourth quartiles, respectively, compared with the first quartile] were found to be related to late diagnosis. EDI level was not related to late HIV diagnosis. CONCLUSIONS: 'Population' seems to be more relevant than EDI to define evidence-based interventions to limit late diagnosis.

Efficacy, safety and patient-reported outcomes of ledipasvir/sofosbuvir in NS3/4A protease inhibitor-experienced individuals with hepatitis C virus genotype 1 and HIV coinfection with and without cirrhosis (ANRS HC31 SOFTRIH study).

OBJECTIVES: Studies evaluating the efficacy and safety of the fixed-dose combination ledipasvir (LDV)/sofosbuvir (SOF) in patients coinfected with HIV-1 and hepatitis C virus (HCV) have mainly included treatment-naïve patients without cirrhosis. We aimed to evaluate the efficacy and safety of this combination in treatment-experienced patients with and without cirrhosis. METHODS: We conducted a multicentre, open-label, double-arm, nonrandomized study in patients coinfected with HIV-1 and HCV genotype 1 with and without cirrhosis, who had good viral suppression on their antiretroviral regimens. All patients were pretreated with a first-generation NS3/4A protease inhibitor (PI) plus pegylated interferon/ribavirin. Patients received a fixed-dose combination of LDV/SOF for 12 weeks, or for 24 weeks if cirrhosis was present. The primary endpoint was a sustained virological response (SVR) 12 weeks after the end of therapy. Secondary endpoints included safety, pharmacokinetics and patient-reported outcomes. RESULTS: Of the 68 patients enrolled, 39.7% had cirrhosis. Sixty-five patients [95.6%; 95% confidence interval (CI): 87.6-99.1%; P < 0.0001] achieved an SVR, with similar rates of SVR in those with and without cirrhosis. Tolerance was satisfactory, with mainly grade 1 or 2 adverse events. Among patient-reported outcomes, only fatigue significantly decreased at the end of treatment compared with baseline [odds ratio (OR): 0.36; 95% CI: 0.14-0.96; P = 0.04]. Mean tenofovir area under the plasma concentration-time curve (AUC) at week 4 was high, with mean ± SD AUC variation between baseline and week 4 higher in cirrhotic than in noncirrhotic patients (3261.57 ± 1920.47 ng/mL vs. 1576.15 ± 911.97 ng/mL, respectively; P = 0.03). Mild proteinuria (54.4%), hypophosphataemia (50.0%), blood bicarbonate decrease (29.4%) and hypokalaemia (13.2%) were reported. The serum creatinine level was not modified. CONCLUSIONS: LDV/SOF provided a high SVR rate in PI-experienced subjects coinfected with HCV genotype 1 and HIV-1, including patients with cirrhosis.

Ageing with HIV: do comorbidities and polymedication drive treatment optimization?

OBJECTIVES: The aim of the study was to describe the ageing HIV-infected population (> 50 years old) and their current antiretroviral therapy (ART), comorbidities and coprescriptions in France in 2013 and to compare them to the younger population. METHODS: A retrospective analysis of a prospectively collected database was performed. The characteristics of patients receiving ART as well as their current ART and their numbers of comorbidities and comedications at the censoring date (1 July 2013) were compared between patients ageing with HIV infection, patients who seroconverted while ageing, and younger patients. RESULTS: We compared 10 318 ageing patients [median age 56 years; 25% interquartile range (IQR) 53-62 years] with 13 302 younger patients (median age 42 years; 25% IQR 36-47 years). The ageing patients were more frequently male than the younger patients (77 vs. 65%). Among the ageing patients, 7025 were diagnosed with HIV infection before 2000 and represented a distinct group, the 'experienced ageing' group, by comparison with the 'recently diagnosed ageing' group. Triple therapy containing a boosted protease inhibitor was used in 28.2% of the patients (vs. 39% and 36% of the younger and "recently diagnosed ageing" groups, respectively); a nonnucleoside reverse transcriptase inhibitor in 27% (vs. 33% and 38%, respectively), an integrase strand transfer inhibitor (INSTI) in 9% (vs. 7% and 9%, respectively), and another regimen (fewer or more than three drugs) in 35.8% (vs. 21% and 16.5%, respectively). "Experienced ageing" patients typically had one or more comorbidities (62.1%) and were receiving at least one comedication (71%). Central nervous system (CNS) agents (prescribed in 44.6% of the "experienced ageing" patients) and antilipidaemics (in 44.2%) were the most frequently prescribed comedications. INSTIs were used in 23% of the population and were used significantly more often in patients with comorbidities and coprescriptions. For all comparisons, P < 0.0001. CONCLUSIONS: In ageing HIV-infected patients, especially those with a long history of HIV infection, comorbidities and coprescriptions are highly prevalent.

Pre-exposure prophylaxis: a useful tool to prevent human immunodeficiency virus infection?

The aim of preventive measures against human immunodeficiency virus (HIV) is to reduce the incidence of HIV infection in the general population and in high-risk groups, such as men having sex with men (MSM), and to reduce the risk that a given individual will contract or spread the virus. Male and female condoms, post-exposure prophylaxis and circumcision are preventive methods currently recognized or promoted worldwide. Although modest success has been reported in a phase-III vaccine trial, other methods are being evaluated, such as vaginal and rectal microbicides, and pre-exposure prophylaxis (PrEP). Herein, we discuss results from prevention trials, especially those focusing on PrEP and particularly on recent results from 'on-demand' PrEP regimens. The efficacy of PrEP (rates of 0%-86%) is strongly correlated with adherence and plasma concentrations of antiretrovirals. Adverse events are rare. Selection of emtricitabine-resistant strains is mainly reported in individuals with an undiagnosed HIV infection using PrEP. PrEP is now strongly recommended in WHO prevention programmes for individuals at substantial risk for HIV with a view to controlling this epidemic by 2030.

Comparative risk of failure of ABC/3TC or TDF/FTC based first-line regimens in patients with a high viral load.

OBJECTIVES: To compare the efficacy, in current clinical practice, of first regimens containing abacavir with lamivudine (ABC/3TC) or tenofovir with emtricitabine (TDF/FTC) in patients with baseline viral load ≥100,000 HIV-1 RNA copies/mL. METHODS: Using a prospective cohort, we selected all patients starting a first HIV regimen based either on ABC/3TC or on TDF/FTC. The propensity score (PS) method was used to limit the indication bias due to the observational nature of the data. Adjusting and weighting methods via PS were used to compare the effectiveness of a first regimen containing ABC/3TC or TDF/FTC. The primary outcome was treatment failure by month 12 (M12). RESULTS: Overall, 2781 patients started an antiretroviral (ARV) regimen with ABC/3TC or TDF/FTC each in combination with efavirenz, boosted atazanavir or boosted darunavir. Among the 2472 uncensored patients before M12, 962 (39%) had a baseline viral load ≥100,000 copies/mL of whom 294 were in treatment failure at or before M12. Our analyses showed no difference between ABC/3TC and TDF/FTC in the risk of treatment failure at M12 in patients starting an ARV regimen with a high viral load (≥100,000 copies/mL). CONCLUSIONS: Using a large prospectively collected cohort of patients seeking care in France, we found no evidence that ABC/3TC based regimens led to more failures than TDF/FTC based ones in patients with high baseline viral loads.

Preexposure prophylaxis (PrEP) of HIV infection in France: a nationwide cross-sectional study (PREVIC study).

Although preliminary studies showed that preexposure prophylaxis (PrEP) lowers the HIV transmission in individuals with HIV, confirmative trials are ongoing and PrEP is not routinely recommended. The aim of this study was to assess whether individuals with HIV share antiretroviral (ARV) drugs for PrEP and to describe awareness and discussion on PrEP in this population. A cross-sectional survey was conducted in France in 23 representative departments of infectious diseases and internal medicine. Physicians administered an anonymous standardized questionnaire to all individuals with HIV receiving ARVs and followed between 24 and 31 October 2011. The questionnaire included items regarding PrEP (awareness; discussion with their close circle, physician or patients' association; experience), personal sociodemographic characteristics, risk behaviors and HIV status of the participants. Five hundred and ninety three participants were recruited: male 74.2% (men who have sex with men 52.4%, heterosexuals 21.6%), member of patient's association 9.8%. Half of them (50.6%) lived with a stable partner and 35.2% with an HIV-negative partner. Almost half (41.8%) were aware and 29.5% had had discussion about PrEP. In logistic regression, awareness and discussion on PrEP were more frequent: (1) among males, in patients' association members (p< 0.001 for both) and in nonheterosexuals (p=0.023 and 0.057, respectively); (2) among women, in those not living with a stable partner (p=0.035 and p=0.03, respectively) or living with an HIV-negative partner (p=0.049 and p=0.083, respectively). One percent of the participants declared having shared ARVs with someone and 8.3% reported PrEP in their close circle. Men reporting PrEP in their close circle shared ARVs more frequently than those who did not (10.3% vs. 0.2%, p < 0.001). Today, individuals with HIV do not seem to widely share personal ARVs for PrEP with seronegative people. A significant number of individuals with HIV are aware of and commonly discuss PrEP.

Evolution of glomerular filtration rate in HIV-infected, HIV-HBV-coinfected and HBV-infected patients receiving tenofovir disoproxil fumarate.

We aimed to compare the evolution of estimated glomerular filtration rate (eGFR) in HIV-, HIV-HBV- and HBV-infected patients treated with tenofovir disoproxil fumarate (TDF). Three groups of patients receiving TDF > 12 months were recruited: 194 HIV-infected patients, 85 HIV-HBV-coinfected patients and 50 HBV-infected patients. eGFR was estimated using the Modification of the Diet in Renal Disease (MDRD) equation. Multivariate regression models were constructed to estimate factors associated with eGFR decrease from baseline. A total of 329 patients were studied. Median follow-up was 2.7 years. Median eGFR decrease was -4.9 (-16.6 to +7.2) mL/min/1.73 m(2) . After multivariate stepwise regression analysis, age (P = 0.0002), non-African origin (P < 0.0001), baseline eGFR (P < 0.0001) and TDF duration (P = 0.02) were associated with eGFR decrease in the whole population, while hypertension, diabetes and type of infection were not. Age (P < 0.0001), non-African origin (P = 0.0004), baseline eGFR (P < 0.0001) and TDF duration (P = 0.007) remained associated with eGFR decline in HIV and HIV-HBV-infected patients, while other variables including HIV risk factor, CDC stage, CD4 and HIV-RNA levels were not. Age (P = 0.03), non-African origin (P = 0.004), baseline eGFR (P < 0.0001) and baseline HBV-DNA > 2000 IU/mL (P = 0.04) were associated with eGFR decline in HBV and HIV-HBV-infected patients, while other variables including HBV risk factor and fibrosis stage were not. Estimated glomerular filtration rate decline under TDF therapy appears mainly associated with older age, non-African origin, higher baseline eGFR and longer TDF administration but not with the type of viral infection. Regular follow-up of renal function, especially tubular function is recommended during TDF therapy.

Pulmonary manifestations of leptospirosis.

BACKGROUND: Pulmonary manifestations in leptospirosis are considered a major complication and are related to a poor prognosis. We present a large series of patients with pulmonary involvement using a practical approach based on the presence of acute respiratory failure (ARF). METHODS: A retrospective study of patients with confirmed leptospirosis. RESULTS: One hundred and sixty-nine patients with a laboratory-confirmed diagnosis of leptospirosis were investigated. One hundred and thirty-four patients (36.7±14 years of age) had pulmonary involvement. Severe pulmonary involvement was defined by evidence of ARF. Univariate analysis found the following factors related to severe pulmonary leptospirosis: dyspnoea (OR=10.14, p<0.0001), pulmonary crepitations (OR=4.8, p<0.0004), abnormal chest X-ray (OR=9.88, p<0.007) with alveolar shadowing (OR=8.12, p<0.0001), oliguria/anuria (OR=5.48, p<0.0001), hepatomegaly (OR=7.11, p< 0.0001), shock (OR=8.38, p< 0.0001), ICU admission (OR=60.08, p< 0.0001), dialysis (OR=4.87, p< 0.001), mechanical ventilation (OR=216, p< 0.0001) and development of nosocomial infection (OR=21.5, p< 0.0001). The mortality rate was significantly different between severe (40%) and non-severe (5.3%) pulmonary forms (OR=11.87, p< 0.0001). Multivariate analysis found two independent factors related to severe pulmonary involvement: dyspnoea (OR=10.18, p< 0.0001) and oliguria/anuria (OR=4.87, p< 0.0009). We performed a multivariate analysis to assess independent factors related to mortality and found: mechanical ventilation requirement (OR=27.85, p< 0.0001) and AST greater than 150 IU/L (OR=4.57, p< 0.02). Haemoptysis was associated with survival (OR=0.2, p< 0.02). CONCLUSIONS: Severe pulmonary involvement in leptospirosis is associated with extensive disease involving other organs. The association of multiple factors is associated with severe forms of the disease and a high mortality rate.

Factors associated with pandemic influenza A/H1N1 vaccine coverage in a French cohort of HIV-infected patients.

BACKGROUND: A mass influenza A/H1N1 vaccination campaign took place in France during the 2009 winter. Overall, 7.9% of the general population was vaccinated. However, vaccine coverage data are missing for at-risk groups. METHODS: A vaccination centre was implemented for HIV-infected patients followed-up in a French University Hospital. Demographical, clinical and biological characteristics were collected. Adjusted odds ratios (aOR) were calculated to identify factors associated with being vaccinated against A/H1N1 influenza. RESULTS: A/H1N1 vaccine coverage was 44.4% (635/1430) in HIV-infected patients. In univariate analysis, uptake of vaccination was significantly associated with male gender, men who have sex with men, age ≥ 50 years, ≥ 1 seasonal influenza risk factor, longer HIV disease, longer duration of antiretroviral therapy, greater number of lines of antiretroviral treatments, lower nadir CD4, recent HIV-RNA<50 copies/ml, previous pneumococcal vaccination, > 2 visits to the unit during the study period and follow-up by a physician who assessed ≥ 100 patients/year (senior physician). CDC stage, recent CD4 count, diabetes, BMI>30 and pregnancy were not associated with vaccination. After multivariate analysis, vaccination remained significantly associated with age ≥ 50 years (aOR 1.56, CI 1.16-2.09), time since HIV diagnosis (aOR per 1 year 1.02, CI 1.00-1.04), previous pneumococcal vaccination (aOR 2.56, CI 1.96-3.34), >2 visits to the unit (aOR 5.09, CI 3.87-6.68) and follow-up by a senior physician (aOR 1.73, CI 1.20-2.48). CONCLUSION: A/H1N1 vaccination was more successful in HIV-infected patients than in the French general population. Organization of the vaccination in a convenient location and implication of the physicians seem to be determining factors for A/H1N1 acceptability in this population.

Proficiency of transient elastography compared to liver biopsy for the assessment of fibrosis in HIV/HBV-coinfected patients.

Transient elastography (TE) is a noninvasive technique to evaluate liver fibrosis. We compared the performance of TE with liver biopsy (LB) in patients with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) coinfection. Patients prospectively underwent TE and LB. The diagnosis accuracy of TE was calculated using receiver operating characteristic (ROC) curves for different stages of fibrosis, and optimal cut-off values were defined. A sequential algorithm combining TE with biochemical score (Fibrotest) is proposed. Fifty-seven patients had both TE and LB (median time: 3 days) and two with proven cirrhosis, only TE. Forty-six (78%) were under antiretroviral therapy with anti-HBV drugs in 98%, and 19 (32%) had elevated alanine aminotransferase (ALT). A significant correlation was observed between liver stiffness measurement (LSM) and METAVIR fibrosis stages (P < 0.0001). Patients with elevated ALT tended to have higher LSM than those with normal ALT. The areas under the ROC curves were 0.85 for significant fibrosis (≥ F2), 0.92 for advanced fibrosis (≥ F3) and 0.96 for cirrhosis. Using a cut-off of 5.9 kPa for F ≥ 2 and 7.6 kPa for F ≥ 3, the diagnosis accuracy was 83% and 86%, respectively. With an algorithm combining TE and Fibrotest, 97% of patients were well classified for significant fibrosis. Using this algorithm, the need for LB can be reduced by 67%. In HIV/HBV-coinfected patients, most of them with normal ALT under antiretroviral treatment including HBV active drugs, TE was proficient in discriminating moderate to severe fibrosis from minimal liver disease.

[Pulmonary manifestations of leptospirosis]. / Manifestations pulmonaires de la leptospirose.

BACKGROUND: Pulmonary manifestations in leptospirosis are considered a major complication, and are related to a poor prognosis. We present a large series of patients with pulmonary involvement using a practical approach based on the presence of acute respiratory failure (ARF). METHODS: A retrospective study of patients with confirmed leptospirosis. RESULTS: 169 patients with a laboratory-confirmed diagnosis of leptospirosis were investigated. 134 patients (36.7 + or - 14 years of age) had pulmonary involvement. Severe pulmonary involvement was defined by evidence of acute respiratory failure. Univariate analysis found the following factors related to severe pulmonary leptospirosis: dyspnoea (OR 10.14, p<0.0001), pulmonary crepitations (OR 4.8, p<0.0004), abnormal chest X Ray (OR 9.88, p<0.007) with alveolar shadowing (OR 8.12, p<0.0001), oliguria/anuria (OR 5.48, p<0.0001), hepatomegaly (OR 7.11, p<0.0001), shock (OR 8.38, p<0.0001), ICU admission (OR 60.08, p<0.0001), dialysis (OR 4.87, p<0.001), mechanical ventilation (OR 216, p<0.0001) and development of nosocomial infection (OR 21.5, p<0.0001). The mortality rate was significantly different between severe (40%) and non-severe (5.3%) pulmonary forms (OR 11.87, p<0.0001). Multivariate analysis found 2 independent factors related to severe pulmonary involvement: dyspnoea (OR 10.18, p<0.0001), and oliguria/anuria (OR 4.87, p<0.0009). We performed a multivariate analysis to assess independent factors related to mortality and found: Mechanical ventilation requirement (OR 27.85, p<0.0001) and ASAT>150 UI/L (OR 4.57, p<0.02). Haemoptysis was associated with survival (OR 0.2, p<0.02). CONCLUSION: Severe pulmonary involvement in leptospirosis is associated with extensive disease involving other organs. The association of multiples factors is associated with severe forms of the disease and a high mortality rate.

Sexually transmitted HCV infection and reinfection in HIV-infected homosexual men.

Multiple, concomitant or successive hepatitis C virus (HCV) infections have been described in injection drug users and following organ transplantation and blood transfusion. However, data on sexual HCV reinfection is scarce. We report sexual HCV reinfection following viral eradication of a first HCV infection in two homosexual HIV-infected men. The first patient acquired HCV genotype 4 infection after resolution of an initial acute HCV genotype 1a infection. The second patient was infected with genotype 1a HCV following remission of an initial acute HCV genotype 4c/d infection. The two subjects were successfully treated with peginterferon alpha-2a and ribavirin for their first and second infection and achieved a sustained virological response on both occasions. Unprotected anal intercourse with multiple partners known to be HIV-positive (serosorting) was the only risk factor for HCV transmission reported by both patients. Therefore, sexual HCV reinfection can occur in homosexual men having unprotected sex and "serosorting" should be considered a risk factor for the sexual transmission of HCV.