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.

Treatment outcomes of integrase inhibitors, boosted protease inhibitors and nonnucleoside reverse transcriptase inhibitors in antiretroviral-naïve persons starting treatment.

OBJECTIVES: Although outcomes of antiretroviral therapy (ART) have been evaluated in randomized controlled trials, experiences from subpopulations defined by age, CD4 count or viral load (VL) in heterogeneous real-world settings are limited. METHODS: The study design was an international multicohort collaboration. Logistic regression was used to compare virological and immunological outcomes at 12 ± 3 months after starting ART with an integrase strand transfer inhibitor (INSTI), contemporary nonnucleoside reverse transcriptase inhibitor (NNRTI) or boosted protease inhibitor (PI/b) with two nucleos(t)ides after 1 January 2012. The composite treatment outcome (cTO) defined success as VL < 200 HIV-1 RNA copies/mL with no regimen change and no AIDS/death events. Immunological success was defined as a CD4 count > 750 cells/µL or a 33% increase where the baseline CD4 count was ≥ 500 cells/µL. Poisson regression compared clinical failures (AIDS/death ≥ 14 days after starting ART). Interactions between ART class and age, CD4 count, and VL were determined for each endpoint. RESULTS: Of 5198 ART-naïve persons in the International Cohort Consortium of Infectious Diseases (RESPOND), 45.4% started INSTIs, 26.0% PI/b and 28.7% NNRTIs; 880 (17.4%) were aged > 50 years, 2539 (49.4%) had CD4 counts < 350 cells/µL and 1891 (36.8%) had VL > 100 000 copies/mL. Differences in virological and immunological success and clinical failure among ART classes were similar across age groups (≤ 40, 40-50 and > 50 years), CD4 count categories (≤ 350 vs. > 350 cells/µL) and VL categories at ART initiation (≤ 100 000 vs. > 100 000 copies/mL), with all investigated interactions being nonsignificant (P > 0.05). CONCLUSIONS: Differences among ART classes in virological, immunological and clinical outcomes in ART-naïve participants were consistent irrespective of age, immune suppression or VL at ART initiation. While confounding by indication cannot be excluded, this provides reassuring evidence that such subpopulations will equally benefit from contemporary ART.

Kaposi sarcoma among people living with HIV in the French DAT'AIDS cohort between 2010 and 2015.

BACKGROUND: Although antiretroviral therapy (ART) has reduced the risk of Kaposi sarcoma (KS), KS cases still occur in HIV-infected people. OBJECTIVE: To describe all KS cases observed between 2010 and 2015 in a country with high ART coverage. METHODS: Retrospective study using longitudinal data from 44 642 patients in the French Dat'AIDS multicenter cohort. Patients' characteristics were described at KS diagnosis according to ART exposure and to HIV-plasma viral load (HIV-pVL) (≤50 or >50) copies/mL. RESULTS: Among the 209 KS cases diagnosed during the study period, 33.2% occurred in ART naïve patients, 17.3% in ART-experienced patients and 49.5% in patients on ART, of whom 23% for more than 6 months. Among these patients, 24 (11.5%) had HIV-pVL ≤50 cp/mL, and 16 (66%) were treated with a boosted-PI-based regimen. The distribution of KS localization did not differ by ART status nor by year of diagnosis. LIMITATIONS: Data on human herpesvirus 8, treatment modalities for KS and response rate were not collected. CONCLUSION: Half of KS cases observed in the study period occurred in patients not on ART, reflecting the persistence of late HIV diagnosis. Factors associated with KS in patients on ART with HIV-pVL ≤50 cp/mL remain to be explored.

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.

Factors associated with deaths from suicide in a French nationwide HIV-infected cohort.

OBJECTIVES: People living with HIV (PLHIV) are at a higher risk of dying by suicide than the general population. Epidemiological data regarding determinants of suicide in PLHIV are scarce. The aim of this study was thus to study demographic, socio-economic, psychiatric history and immunovirological characteristics associated with death from suicide in the French multicenter Dat'AIDS cohort, from January 2000 to July 2013. METHODS: This was a nested case-control study. All deceased PLHIV during the study period who died by suicide and whose medical files could be checked were included as cases. Controls were selected using incidence density sampling. For each case, up to four controls were selected among all actively followed PLHIV at the index date (date of death of cases). Controls were matched for time from HIV diagnosis (5-year periods) and clinical centre. RESULTS: Seventy cases and 279 controls were included in the study. By multivariable analysis, the factors significantly associated with death from suicide were: not having children, active or substituted drug consumption, alcohol intake > 20 g/day or history of alcohol abuse, history of depressive disorder and/or of attempted suicide, and psychotropic drug intake. Conversely, age, gender, country of birth, positive HCV serology and HIV-related factors, such as AIDS status, use of combination antiretroviral therapy (cART), nadir and current CD4 counts and HIV viral load, were not significantly associated with the risk of death from suicide. CONCLUSIONS: In the cART era, HIV-related factors are not associated with a higher risk of suicide mortality. Suicide prevention measures should target PLHIV with the psychological morbidities observed in our cohort.

Long-term effectiveness of recommended boosted protease inhibitor-based antiretroviral therapy in Europe.

OBJECTIVES: The aim of the study was to evaluate the long-term response to antiretroviral treatment (ART) based on atazanavir/ritonavir (ATZ/r)-, darunavir/ritonavir (DRV/r)-, and lopinavir/ritonavir (LPV/r)-containing regimens. METHODS: Data were analysed for 5678 EuroSIDA-enrolled patients starting a DRV/r-, ATZ/r- or LPV/r-containing regimen between 1 January 2000 and 30 June 2013. Separate analyses were performed for the following subgroups of patients: (1) ART-naïve subjects (8%) at ritonavir-boosted protease inhibitor (PI/r) initiation; (2) ART-experienced individuals (44%) initiating the new PI/r with a viral load (VL) ≤500 HIV-1 RNA copies/mL; and (3) ART-experienced patients (48%) initiating the new PI/r with a VL >500 copies/mL. Virological failure (VF) was defined as two consecutive VL measurements >200 copies/mL ≥24 weeks after PI/r initiation. Kaplan-Meier and multivariable Cox models were used to compare risks of failure by PI/r-based regimen. The main analysis was performed with intention-to-treat (ITT) ignoring treatment switches. RESULTS: The time to VF favoured DRV/r over ATZ/r, and both were superior to LPV/r (log-rank test; P < 0.02) in all analyses. Nevertheless, the risk of VF in ART-naïve patients was similar regardless of the PI/r initiated after controlling for potential confounders. The risk of VF in both treatment-experienced groups was lower for DRV/r than for ATZ/r, which, in turn, was lower than for LPV/r-based ART. CONCLUSIONS: Although confounding by indication and calendar year cannot be completely ruled out, in ART-experienced subjects the long-term effectiveness of DRV/r-containing regimens appears to be greater than that of ATZ/r and LPV/r.

Hospitalization of HIV positive patients: Significant demand affecting all hospital sectors.

BACKGROUND: In a context of the evolution of severe morbidities in patients living with HIV (PLWH), the aim of this study was to describe reasons for hospitalization and the mode of care for the patients requiring hospitalization. METHODS: All admissions (≥24h) of PLWH to 10 hospitals in the south of Paris (COREVIH Ile-de-France Sud) between 1/1/2011 and 12/31/2011 were identified. The hospital database and the file of patients followed in the HIV referral department of each hospital were matched. Detailed clinical and biological data were collected, by returning to the individual medical records, for a random sample (65% of hospitalized patients). RESULTS: A total of 3013 hospitalizations (1489 patients) were recorded in 2011. The estimated rate of hospitalized patients was about 8% among the 10105 PLWH routinely managed in COREVIH Ile-de-France Sud in 2011. The majority (58.5%) of these hospitalizations occurred in a unit other than the HIV referral unit. Non-AIDS-defining infections were the main reason for admission (16.4%), followed by HIV-related diseases (15.6%), hepatic/gastrointestinal diseases (12.0%), and cardiovascular diseases (10.3%). The median length of stay was 5 days overall (IQR: 2-11), it was longer among patients admitted to a referral HIV care unit than to another ward. HIV infection had been diagnosed >10 years previously in 61.4% of these hospitalized patients. They often had associated comorbidities (coinfection HCV/HVB 40.5%, smoking 45.8%; hypertension 33.4%, dyslipidemia 28.8%, diabetes 14.8%). Subjects over 60 years old accounted for 15% of hospitalized patients, most of them were virologically controlled under HIV treatment, and cardiovascular diseases were their leading reason for admission. CONCLUSION: Needs for hospitalization among PLWH remain important, with a wide variety in causes of admission, involving all hospital departments. It is essential to prevent comorbidities to reduce these hospitalizations, and to maintain a link between the management of PLWH, that becomes rightly, increasing ambulatory, and recourse to specialized inpatient services.

Psychiatric and substance use disorders in HIV/hepatitis C virus (HCV)-coinfected patients: does HCV clearance matter? [Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS) HEPAVIH CO13 cohort].

OBJECTIVES: The objective of this nested study was to assess the prevalence of psychiatric disorders in a sample of HIV/hepatitis C virus (HCV)-coinfected patients according to their HCV status. METHODS: The nested cross-sectional study, untitled HEPAVIH-Psy survey, was performed in a subset of HIV/HCV-coinfected patients enrolled in the French Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS) CO13 HEPAVIH cohort. Psychiatric disorders were screened for using the Mini International Neuropsychiatric Interview (MINI 5.0.0). RESULTS: Among the 286 patients enrolled in the study, 68 (24%) had never received HCV treatment, 87 (30%) were treatment nonresponders, 44 (15%) were currently being treated and 87 (30%) had a sustained virological response (SVR). Of the 286 patients enrolled, 121 patients (42%) screened positive for a psychiatric disorder other than suicidality and alcohol/drug abuse/dependence, 40 (14%) screened positive for alcohol abuse/dependence, 50 (18%) screened positive for drug abuse/dependence, 50 (17.5%) were receiving an antidepressant treatment and 69 (24%) were receiving an anxiolytic. Patients with an SVR did not significantly differ from the other groups in terms of psychiatric disorders. Patients receiving HCV treatment screened positive less often for an anxiety disorder. The highest rate of drug dependence/abuse was among HCV treatment-naïve patients. CONCLUSIONS: Psychiatric disorders were frequent in HIV/HCV-coinfected patients and their rates were comparable between groups, even for patients achieving an SVR. Our results emphasize the need for continuous assessment and care of coinfected patients, even after HCV clearance. Drug addiction remains an obstacle to access to HCV treatment. Despite the recent advent and continued development of directly acting antiviral agents (DAAs), it is still crucial to offer screening and comprehensive care for psychiatric and addictive disorders.

Frequency dependence of capnography in anesthetized rabbits.

Aspirative capnography may be of help to diagnose early childhood asthma, but clinical usefulness in young children is limited by the relatively high respiratory rate. This study aimed to characterize the [Formula: see text] time course during airway constriction in 8 anesthetized rabbits, artificially ventilated at 30, 60 and 80breaths/min. Methacholine was inhaled to double the respiratory resistance measured at 8Hz by the forced oscillation technique. The capnogram shape changed in response to both methacholine and ventilatory frequency. Slope of phase II, the peak of first-order time derivative and trough of the second-order time derivative of the [Formula: see text] signal, were significantly attenuated after methacholine compared with baseline at all breathing rates (p<0.02). Moreover, significant correlations between respiratory reactance and resistance were observed with the phase III slope and the angle described by phase II and phase III (p<0.01). It is concluded that capnography may be useful to identify acute airway changes related to bronchoconstriction, even at high breathing frequencies.

[Value of the Linton-Nachlas balloon for the management of post-partum hemorrhage: a series of 25 cases]. / Intérêt de la sonde de Linton-Nachlas dans la prise en charge des hémorragies du post-partum : une série de 25 cas.

OBJECTIVES: Post-partum hemorrhage (PPH) is the first cause of maternal mortality in France. Uterine tamponade is an alternative in the management of PPH. We investigated the efficiency of the Linton-Nachlas balloon in treating severe PPH in a French Guiana center where interventional radiology is not available. MATERIALS AND METHODS: In this retrospective study, 25 women with severe PPH were included. Severe PPH is defined by the persistence of PPH despite sulprostone treatment. All women included in the study gave birth by vaginal delivery. The Linton-Nachlas balloon (Coloplast(®), France) used for digestive hemorrhage was inserted transvaginally. The primary endpoint for the efficiency was stopping PPH. RESULTS: The use of this balloon stopped the bleeding for 24 out of 25 patients (96 %). There was one case in which the treatment by the balloon was a failure. In that case, vaginal packing stopped the hemorrhage. No patient needed any complementary surgical treatment. CONCLUSION: This technique is a non-invasive, inexpensive, easy and efficient treatment. Most of the time, its use can stop hemorrhage and preserve fertility of young women wishing further pregnancies.

Efficacy, safety, and pharmacokinetics of once-daily boosted darunavir in pretreated HIV-infected patients.

OBJECTIVE AND METHODS: The efficacy and safety of switching to a combined regimen containing darunavir/ritonavir (DRV/r) was investigated in a retrospective study. RESULTS: Sixty-six experienced patients receiving once-daily DRV/r (900/100 mg) in various regimens were included (median age 51 y; male 82%; Centers for Disease Control and Prevention (CDC) stages B or C 70%). The number of patients with plasma HIV RNA < 50 copies/ml increased from 71% (45/63) at baseline (before switch) to 84% (52/62) at visit 1 (weeks 3-11), and to 92% (60/65) at visit 2 (weeks 12-24). CD4 cells increased from 498 ± 201 cells/mm³ at baseline to 567 ± 232 cells/mm³ by visit 2. Good digestive and metabolic tolerance was observed. The median steady-state DRV plasma concentration, measured 24 ± 4 h after the last drug intake, was 1427 ng/ml. All DRV plasma concentrations were above the protein-binding corrected median effective concentration (EC50) for the wild-type virus (55 ng/ml). CONCLUSIONS: Once-daily DRV/r (900/100 mg) was efficacious in pretreated patients, with safe responses.

Prevalence of CXCR4-tropic viruses in clustered transmission chains at the time of primary HIV-1 infection.

During 2003-2010, 555 strains isolated from sexually-infected patients at the time of primary HIV-1 infection (PHI) were characterized. Tree topology revealed that 11.7% of PHIs segregated into transmission clusters. CXCR4-usage was identified in 27 strains (4.9%) and was significantly associated with subtype B (p 0.003) and low CD4 cell count (p 0.01). In clustered and unique PHIs, the prevalence of CXCR4-tropic strains was 1.5% and 5.3%, respectively (p 0.35). Our results are in line with the hypothesis of a mucosal bottleneck contributing to the high prevalence of CCR5 variants during PHI.

High frequency of vitamin D deficiency in HIV-infected patients: effects of HIV-related factors and antiretroviral drugs.

OBJECTIVES: The aim of this study was to assess 25-hydroxyvitamin D (vitamin D) status in an HIV-infected adult population and to define HIV- and antiretroviral-related factors associated with vitamin D deficiency. METHODS: Using data from a prospective cohort of HIV-infected adult patients followed in five French centres (Dat'AIDS cohort), we evaluated the prevalence of vitamin D deficiency/insufficiency (<30 ng/mL). A multiple linear regression model was used to examine risk factors for vitamin D deficiency (≤10 ng/mL). RESULTS: Vitamin D deficiency/insufficiency was observed in 86.7% of the 2994 patients, including 55.6% with vitamin D insufficiency and 31.1% with vitamin D deficiency. In multivariate analysis, factors associated with vitamin D deficiency were current smoking [adjusted OR (aOR) 1.55], estimated glomerular filtration rate ≥90 mL/min/1.73 m(2) (aOR 1.51), vitamin D measurement not performed in summer (aOR 0.27), CD4 <350 cells/mm(3) (aOR 1.37 for CD4 200 to <350 and 1.62 for CD4 <200 cells/mm(3)) and antiretroviral therapy (aOR 2.61). Gender, body mass index, age, coinfection and previous AIDS were not associated factors. In the antiretroviral-treated population (n = 2660), besides the same factors found in the whole population, efavirenz was the only drug to be significantly associated with deficiency, with an aOR of 1.89 (95% CI 1.45-2.47). CONCLUSIONS: Vitamin D deficiency is frequent in this HIV-infected population. Patients on antiretroviral therapy are at higher risk of vitamin D deficiency than antiretroviral-naive patients, with an increased risk in patients receiving efavirenz. No effect of the other antiretrovirals, including the latest (etravirine, darunavir, raltegravir), was found.

Lipid profiles for etravirine versus efavirenz in treatment-naive patients in the randomized, double-blind SENSE trial.

BACKGROUND: Etravirine is approved for use in treatment-experienced patients at a dose of 200 mg twice daily. Efavirenz has been associated with greater increases in serum lipids compared with other non-nucleosides in randomized trials of first-line treatment. METHODS: In this double-blind, placebo-controlled trial, 157 treatment-naive patients with HIV RNA >5000 copies/mL were randomized 1:1 to either 400 mg of etravirine once daily (n=79) or 600 mg of efavirenz once daily (n=78) plus two nucleoside analogues (either abacavir/lamivudine, zidovudine/lamivudine or tenofovir/emtricitabine) for 48 weeks. Lipids were measured under fasting conditions at baseline and all visits to Week 48. Clinicaltrials.gov identifier: NCT00903682. RESULTS: Overall, the patients had a median baseline CD4 count of 302 cells/mm(3) (range 74-722) and a median HIV RNA of 4.8 log(10) copies/mL (range 3.5-6.6). Both the non-nucleosides and the nucleoside analogues used caused changes in serum lipids. In the efavirenz arm, patients showed significantly larger increases in high-density lipoprotein (HDL) (+0.15 mmol/L, P=0.004), low-density lipoprotein (LDL) (+0.35 mmol/L, P=0.005), total cholesterol (+0.61 mmol/L, P<0.0001) and triglycerides (+0.33 mmol/L, P=0.03) at Week 48 compared with the etravirine arm. Across the two arms, patients taking abacavir/lamivudine showed greater increases in total cholesterol (+0.47 mmol/L, P=0.005) compared with patients taking tenofovir/emtricitabine. There were fewer grade 3/4 elevations in total cholesterol, LDL and triglycerides in the etravirine arm (2 patients, 1 patient and 0 patients, respectively) versus the efavirenz arm (8 patients, 6 patients and 2 patients, respectively). CONCLUSIONS: In the SENSE trial, first-line treatment with 400 mg of etravirine once daily plus two nucleoside analogues led to fewer grade 3 or 4 lipid elevations compared with efavirenz plus two nucleoside analogues.

Kidney transplantation in HIV-positive patients: report of our first 7 cases.

INTRODUCTION: Infection with human immunodeficiency virus (HIV) is associated with end-stage renal disease (ESRD). Although many teams initially were reluctant to offer kidney transplantation as a therapeutic option in HIV-positive patients with ESRD, new drug regimens introduced in the late 1990s have dramatically improved the life expectancy in these patients. OBJECTIVE: To report the results of the first 7 kidney transplantation procedures in HIV-positive patients at our institution. PATIENTS AND METHODS: Patients were selected to minimize the risks of HIV disease progression, opportunistic infections, and tumors. Protease-inhibitor therapies were suspended because of possible interaction with immunosuppression drugs. The induction regimen did not include lymphocyte-depleting drugs. After undergoing transplantation, patients were monitored by the transplantation and infectious disease teams. RESULTS: To date, all patients are alive with functioning grafts. We did not observe any episodes of acute rejection, and there were few adverse events. Drug tolerance was good for both immunosuppression and antiretroviral therapies. CONCLUSION: Kidney transplantation in HIV-positive patients with ESRD is warranted. Provided that patients are carefully selected, good results can be achieved with few adverse events, episodes of acute rejection, and drug interactions. Posttransplantation, these patients must be closely monitored by both the transplantation and infectious diseases teams to ensure optimal management.

Safety and efficacy of raltegravir in HIV-infected transplant patients cotreated with immunosuppressive drugs.

Solid organ transplantations (SOT) are performed successfully in selected HIV-infected patients. However, multiple and reciprocal drug-drug interactions are observed between antiretroviral (ARV) drugs and calcineurin inhibitors (CNIs) through CYP450 metabolization. Raltegravir (RAL), a novel HIV-1 integrase inhibitor, is not a substrate of CYP450 enzymes. We retrospectively reviewed the outcomes of 13 HIV-infected transplant patients treated by an RAL + two nucleosidic reverse transcriptase inhibitor (NRTI) regimen, in terms of tolerability, ARV efficacy (plasma viral load, CD4 cell count), drug interactions, RAL pharmacokinetics and transplant outcome. Thirteen patients with liver (n = 8) or kidney (n = 5) transplantation were included. RAL was initiated (400 mg BID) either at time of transplantation (n = 6), or after transplantation (n = 7). Median RAL trough concentration was 507 ng/mL (176-890), which is above the in vitro IC95 for wild type HIV-1 strains (15 ng/mL). Target trough levels of CNIs were promptly obtained with standard dosages of tacrolimus or cyclosporine. RAL tolerability was excellent. There was no episode of acute rejection. HIV infection remained controlled. After a median follow-up of 9 months (range: 6-14), all patients were alive with satisfactory graft function. The use of an RAL + two NRTI-based regimen is a good alternative in HIV-infected patients undergoing SOT.

Atazanavir in patients with persistent viral replication despite HAART: results from the French prospective NADIS cohort.

OBJECTIVE: To assess virological efficacy of a ritonavir-boosted atazanavir (ATV/r)-containing regimen in patients with persistent viral replication despite HAART. PATIENTS AND METHOD: Prospective cohort of French HIV-infected patients. Patients were included if pretreated and viral load (VL) >400 copies/mL at the time of ATV/r first prescription (baseline). Demographic and epidemiologic data, therapeutic history, and clinical and biological values at baseline and during follow-up were analyzed. Primary endpoint was failure of the regimen defined as either VL>400 copies/mL at Week 24 or treatment interruption before Week 24. Multivariate analysis was performed of baseline characteristics related with treatment failure. RESULTS: There were 424 patients with available data. Primary endpoint was met by 36%: 24% VL>400 copies/mL and 12% treatment interruption. Treatment interruption due to drug-related toxicity was significantly more frequent in women (20.5% vs. 8.8%, p= .001). Female gender (adjusted odds ratio [OR]=1.91), previous use of lopinavir (LPV; OR=2.76), number of new drugs and of active drugs in the regimen (OR=0.48 and 0.3, respectively), and baseline VL (OR=1.75) were independently related with treatment failure. CONCLUSION: ATV/r-containing regimens, because of low pill burden and good tolerance, can be a useful strategy as long as the patients did not suffer previous LPV failures. The issue of gender deserves further studies in larger populations.

[Demographic, clinical, immunovirological and therapeutic features of 8714 HIV infected French patients included in the Nadis Hospital Cohorte in 2006]. / Caractéristiques démographiques, cliniques, immunovirologiques et thérapeutiques de 8714 patients infectés par le VIH de la cohorte Nadis en 2006.

OBJECTIVES: The authors had for aim to describe demographic, immunovirilogical and therapeutic characteristics of HIV infected patients enrolled in a French clinical cohort. STUDY DESIGN: A cross-sectional analysis was performed on 30 September 2006, among patients followed in seven French University Medical Centers using the Nadis computerized medical file. RESULTS: Among 8714 patients enrolled (median age 43 years: 15-86, sex ratio 2.37), sexual transmission was the most frequent route of infection (heterosexual: 39.3%, homosexual: 34.8%). HIV and hepatitis C (HCV) or B (HBV) co-infection rates were at 19.2 and 5.8%, respectively. The number of patients who had a triple infection with HIV-HBV-HCV were 1.7%. CDC aids classification was A: 56.7%, B: 19.6%, C: 23.7%. We observed a higher proportion of female patients and an increase of the median age. The number of patients receiving antiretroviral therapy (ARV) at the study date were 81.7%, 11.7% were ARV-naive and 6,6% on a treatment interruption. Under ARV, the median CD4 count was 478cells per millimetre cube (1 to 2166) and 84.8% of patients had an undetectable viral load (VL). Among these patients, 10% had a CD4 cell count inferior or equal to 200 per millimetre cube. Patients followed in centers that participated in this study were different regarding sex, transmission routes, and HBV or HCV co-infection rates, but not regarding the proportion of patients with undetectable VL. ARV combination included more frequently protease inhibitors than nonnucleosidic reverse transcriptase (50% versus 26.2%). CONCLUSION: Among the 8714 HIV-infected patients on ARV, 85% had a VL inferior or equal to 400 per millilitre, 10% of whom had CD4 cell counts inferior or equal to 200 per millimetre cube. The proportion of patients on ARV with undetectable VL was comparable in centers who participated in this study.