No Association Between HLA-B*57:01 and Prevalence and/or Outcome of Progressive Multifocal Leukoencephalopathy in a French Nationwide Human Immunodeficiency Virus Cohort.

Among 34,351 patients living with human immunodeficiency virus with available HLA-B*57:01 included in the Dat'AIDS cohort, 194 patients (0.56%) had a history of progressive multifocal leukoencephalopathy (PML) and 1,746 (5.08%) were carriers of HLA-B*57:01. The frequency of HLA-B*57:01 was similar among patients with history of PML compared with patients without a history of PML (6.19% [95% confidence interval, CI 2.8%-9.6%] vs. 5.08% [95% CI 4.8%-5.3%]; p = .48). Among patients with PML, clinical and biological characteristics at PML diagnosis and the PML outcome were not different according to HLA-B*57:01 status.

Drastic Reduction in Time to Controlled Viral Load in People With Human Immunodeficiency Virus in France, 2009-2019: A Longitudinal Cohort Study.

BACKGROUND: Aspirational targets to end AIDS by 2030 include having 95% of people with human immunodeficiency virus (HIV; PWH) diagnosed, 95% treated, and 95% with controlled viral load (VL). Our objective was to describe, using a large French prospective cohort, the median transition times through the cascade of care between 2009 and 2019. METHODS: We analyzed patients whose first HIV diagnosis was made between 1 January 2009 and 31 December 2019. Using the Kaplan-Meier method, we estimated the time to linkage to care (from HIV diagnosis to first biological assessment), to treatment (date of first antiretroviral therapy [ART] prescription), and to controlled VL (first value <200 copies/mL). Analyses were disaggregated by time periods and patients' characteristics. Censoring date was 31 December 2021. RESULTS: Among the 16 864 patients linked to care since 2009, the median [Q1; Q3] time from HIV diagnosis to controlled VL decreased from 254 [127-745] to 73 [48-132] days in 2009-2011 and 2018-2019, respectively. Transition times from linkage to care to first ART decreased from 67 [17; 414] in 2009-2011 to 13 [5; 26] days in 2018-2019, and from ART to controlled VL from 83 [35; 130] in 2009-2011 to 38 [28; 90] days in 2018-2019. Differences were observed depending on patients' characteristics. CONCLUSIONS: We describe drastic reductions in transition time through the cascade of care, allowing reduction in the transmission period following each new infection. Delayed diagnosis remains the main obstacle to ending AIDS in the next decade.

No increased risk of Kaposi sarcoma relapse in patients with controlled HIV-1 infection after switching protease inhibitor-based antiretroviral therapy.

OBJECTIVES: Our aim was to assess if switching from a protease inhibitors (PI)-based regimen to a PI-free one is associated with an increased risk of Kaposi Sarcoma (KS) relapse among patients living with HIV (PLHIV) with history of KS and controlled HIV replication. METHODS: In a retrospective analysis of the prospectively collected Dat'AIDS database we selected patients who both had a past KS history and a HIV-1 viral load below 200 copies/mL while being PI-treated. We searched for KS relapses while persistent virological success was maintained for at least 6 months, whether patients kept taking the PI, or switched to PI-free regimen. RESULTS: Among the 216 patients with past KS event and a history of HIV-1 infection efficiently treated by a PI-based regimen, 148 patients (68.5%) later switched to a PI-sparing regimen. Their baseline characteristics were not different from non-switching patients. We described 7 cases of relapse (3.2% of the 216 patients). Five cases of relapse occurred in switching patients (3.4%). The remaining two relapses occurred in PI-treated patients (2.9%). At KS relapse, CD4 cell count was 459 cells/µL (range 225-560) for switching patients, compared with 362 and 136 cells/µL for the other two patients. CONCLUSIONS: In this large cohort of PLHIV with a history of KS and ART-controlled HIV replication, KS relapses were described in 3.2% of the patients, and were not more frequent when a PI-containing ART regimen has been switched to a PI-free regimen. Our results do not support a specific effect of PI on KS.

Reaching the Second and Third Joint United Nations Programme on HIV/AIDS 90-90-90 Targets Is Accompanied by a Dramatic Reduction in Primary Human Immunodeficiency Virus (HIV) Infection and in Recent HIV Infections in a Large French Nationwide HIV Cohort.

BACKGROUND: In late 2013, France was one of the first countries to recommend initiation of combination antiretroviral therapy (cART) irrespective of CD4 cell count. METHODS: To assess the impact of achieving the second and third Joint United Nations Programme on HIV/AIDS 90-90-90 targets (ie, 90% of diagnosed people on sustained cART, and, of those, 90% virologically controlled) on human immunodeficiency virus (HIV) incidence, we conducted a longitudinal study to describe the epidemiology of primary HIV infection (PHI) and/or recent HIV infection (patients with CD4 cell count ≥500/mm3 at HIV diagnosis; (PRHI) between 2007 and 2017 in a large French multicenter cohort. To identify changes in trends in PHI and PRHI, we used single breakpoint linear segmented regression analysis. RESULTS: During the study period, 61 822 patients were followed in the Dat'AIDS cohort; 2027 (10.0%) had PHI and 7314 (36.1%) had PRHI. The second and third targets were reached in 2014 and 2013, respectively. The median delay between HIV diagnosis and cART initiation decreased from 9.07 (interquartile range [IQR], 1.39-33.47) months in 2007 to 0.77 (IQR, 0.37-1.60) months in 2017. A decrease in PHI (-35.1%) and PRHI (-25.4%) was observed starting in 2013. The breakpoints for PHI and PRHI were 2012.6 (95% confidence interval [CI], 2010.8-2014.4) and 2013.1 (95% CI, 2011.3-2014.8), respectively. CONCLUSIONS: Our findings show that the achievements of 2 public health targets in France and the early initiation of cART were accompanied by a reduction of about one-third in PHI and PRHI between 2013 and 2017. CLINICAL TRIALS REGISTRATION: NCT02898987.

Long-term safety and vaccine-induced seropositivity in healthy volunteers from HIV vaccine trials.

BACKGROUND: The ANRS COV1-COHVAC cohort was a long-term safety cohort of healthy volunteers who received preventive HIV-vaccine candidates in 17 phase I/II clinical trials. METHODS: Data collected from the first vaccine candidate administration and annually after inclusion in the cohort included grade 3/4 adverse events and all grade adverse events suggestive of neurological, ophthalmological and immune disorders, self-administered questionnaires on behaviors and HIV ELISA results. Age-and-sex-standardized mortality ratios (SMRs) were calculated with respect to the French population. The cohort was early terminated in 2016 due to the absence of safety signal. RESULTS: Of 496 volunteers, 488 were included: 355 in the 7-year prospective follow-up and 133 in the retrospective data collection only. The total follow-up after the first vaccination was 4934 person-years (median: 10 years) and 270 (76%) volunteers completed their follow-up. No relevant adverse event possibly related to the vaccine was reported. Breast cancer incidence and woman mortality did not differ from those of the French general population (standardized incidence ratio = 1.47, P = 0.45 and SMR = 0.65, P = 0.28, respectively) while man mortality was significantly lower (SMR = 0.26, P = 0.0003). At the last visit, 21/29 (72%) volunteers who received the recombinant HIV gp160 protein still showed vaccine-induced seropositivity after a median follow-up of 23 years. Only a few volunteers reported risky sexual practices (men: 20/192, women: 2/162). CONCLUSION: Volunteers showed a sustained high commitment. No long-term safety alert was identified during the postvaccine follow-up. Participating in vaccine trials did not increase risky behaviors for HIV infection. Vaccine-induced seropositivity may persist for more than 23 years after receiving rgp160.

HIV-related excess mortality and age-related comorbidities in patients with HIV aged ≥60: a relative survival analysis in the French Dat'AIDS cohort.

OBJECTIVE: The objective was to evaluate the association between age-related comorbidities (ARCs) and 5-year HIV-related excess mortality in people living with HIV aged ≥60 years. DESIGN: Cohort study using relative survival analysis (Estève's model). SETTING: The French multicentre prospective Dat'AIDS cohort that involves 12 French hospitals. PARTICIPANTS: Inclusion of 1415 HIV-1 infected patients actively followed aged ≥60 years on January 2008, with a 5-year follow-up period in the late combination antiretroviral therapy era. RESULTS: Among 1415 patients included, 154 died. By multivariable analysis, factors predictive of 5-year HIV-related excess mortality were non-AIDS-related cancer (adjusted excess HR (aEHR)=2.94; 95% CI 1.32 to 6.57), cardiovascular disease (aEHR=6.00; 95% CI 2.45 to 14.65), chronic renal disease (aEHR=4.86; 95% CI 2.24 to 10.53), cirrhosis (aEHR=3.58; 95% CI 1.25 to 10.28), hepatitis C co-infection (aEHR=3.63; 95% CI 1.44 to 9.12), body mass index<18.5 kg/m² (aEHR=4.10; 95% CI 1.61 to 10.48) and having a CD4 cell count ≤200/mm3 (aEHR=5.79; 95% CI 2.28 to 14.69). CONCLUSIONS: ARCs, particularly cardiovascular disease and chronic renal disease, are predictive of HIV-related excess mortality, with an increase in hazard similar to that of CD4 cell count. TRIAL REGISTRATION NUMBER: NCT02898987.

Reaching the WHO target of testing persons in jails in prisons will need diverse efforts and resources.

BACKGROUND: The Caribbean is the second most affected region in the world by human immunodeficiency virus (HIV), and HIV prevalence is significantly higher among persons in jails and prisons than in the free population. The aim of our study was to assess the screening rates of HIV, hepatitis B and C, syphilis and human T cell leukaemia virus type 1 among newly-arrived persons in 2014, at Ducos facility in Martinique and the testing process performance. METHODS: This is an observational monocentric study conducted within the prison's health unit. The study population consisted of all individuals incarcerated between 01/01/14 and 31/12/14. At the initial medical visit, HIV and STI testing were proposed to every newcomer. The rate of acceptance was calculated, as well as the screening process performance. RESULTS: In 2014 778 new persons were incarcerated, among those, 461 (59.3%) were tested. The main reasons for missing the testing opportunity were due to organization of the judiciary system (persons on electronic monitoring or day parole, transferred or quickly released before completion of the process) or to individual refusal. Finally, 75 persons did not get their results (all of them negative), 41 of them due to the medical staff work overload. CONCLUSIONS: HIV and STI testing rates among newcomers at Ducos have notable room for improvement. The future availability of combined (HIV, HBV, HCV and syphilis) rapid tests may be very useful in case of short term incarceration, if their cost is not prohibitive. Reaching higher levels of testing will also require more resources.

Derivation and internal validation of a mortality risk index for aged people living with HIV: The Dat'AIDS score.

OBJECTIVE: The objective was to develop a multivariable prognostic index for overall mortality over a five-year span integrating classical HIV biomarkers and comorbidities in people living with HIV (PLHIV) aged 60 or older. DESIGN: Prospective multicenter cohort study from the French Dat'AIDS cohort. METHODS: All HIV-1 infected patients aged 60 years or older on 1st January 2008 were included. Sociodemographic data, CD4 cell count, CD4 nadir, HIV viral load, history of comorbidities, hepatitis co-infections and laboratory parameters at baseline were considered as potential prognostic variables. Primary outcome was all-cause mortality. RESULTS: Among 1415 patients included, we derived a score comprising the following predictors: Age (65-74: 1 point; ≥75: 8 points), CD4 cell count (200-349: 3 points; <200: 6 points), non-HIV related cancer (6 points), cardiovascular disease (8 points), estimated glomerular filtration rate (30-59 mL/min/1.73m2: 5 points; <30mL/min/1.73m2: 16 points), cirrhosis (13 points), low body mass index (<18.5 kg/m2, 10 points), anemia (6 points). Mean observed score was 7.0 ± 8.0 and ranged from 0 to 45. Score categories defined 4 risk groups for mortality: low, moderate, high and very high risk (5-year survival probability 0.95 (95%CI[0.93-0.97]), 0.90 (95%CI[0.87-0.92]), 0.77 (95%CI[0.68-0.84]) and 0.54 (95%CI[0.43-0.63]) respectively). The score showed good discrimination (C-statistic = 0.76) and calibration. CONCLUSIONS: We propose a multivariable prognostic score for mortality among PLHIV aged 60 or over, who will become the predominant population in future years in western populations. It could be a useful tool for research, for developing preventive and treatment strategies according to risk group, and for risk assessment by clinicians.

Modeling HIV-HCV coinfection epidemiology in the direct-acting antiviral era: the road to elimination.

BACKGROUND: HCV treatment uptake has drastically increased in HIV-HCV coinfected patients in France since direct-acting antiviral (DAA) treatment approval, resulting in HCV cure in 63% of all HIV-HCV patients by the end of 2015. We investigated the impact of scaling-up DAA on HCV prevalence in the whole HIV population and in various risk groups over the next 10 years in France using a transmission dynamic compartmental model. METHODS: The model was based on epidemiological data from the French Dat'AIDS cohort. Eight risk groups were considered, including high-risk (HR) and low-risk (LR) men who have sex with men (MSM) and male/female heterosexuals, intra-venous drug users, or patients from other risk groups. The model was calibrated on prevalence and incidence data observed in the cohort between 2012 and 2015. RESULTS: On January 1, 2016, 156,811 patients were registered as infected with HIV in France (24,900 undiagnosed patients) of whom 7938 (5.1%) had detectable HCV-RNA (722 undiagnosed patients). Assuming a treatment coverage (TC) rate of 30%/year (i.e., the observed rate in 2015), model projections showed that HCV prevalence among HIV patients is expected to drop to 0.81% in 2026. Sub-analyses showed a similar decrease of HIV-HCV prevalence in most risk groups, including LR MSM. Due to higher infection and reinfection rates, predicted prevalence in HR MSM remained stable from 6.96% in 2016 to 6.34% in 2026. Increasing annual TC rate in HR MSM to 50/70% would decrease HCV prevalence in this group to 2.35/1.25% in 2026. With a 30% TC rate, undiagnosed patients would account for 34% of HCV infections in 2026. CONCLUSIONS: Our model suggests that DAA could nearly eliminate coinfection in France within 10 years for most risk groups, including LR MSM. Elimination in HR MSM will require increased TC.

Low CD4/CD8 Ratio Is Associated with Non AIDS-Defining Cancers in Patients on Antiretroviral Therapy: ANRS CO8 (Aproco/Copilote) Prospective Cohort Study.

OBJECTIVES: To study the association between CD4/CD8 ratio and morbidity in HIV-infected patients on antiretroviral therapy (ART). METHODS: The APROCO/COPILOTE cohort enrolled patients initiating a protease inhibitor-containing ART in 1997-1999. The association between occurrence of first non AIDS-defining severe events (NADE) and time-dependent measures of immune restoration was assessed by 4 Cox models with different definitions of restoration, CD4+ cell counts (CD4), CD4/CD8 ratio, both CD4 and CD4/CD8 ratio, or a composite variable (CD4< 500/mm3, CD4 > 500/mm3 and CD4/CD8 ratio < 1, CD4 > 500/mm3 and CD4/CD8 ratio > 1). Models adjusted on baseline characteristics and time-dependent viral load were compared using Akaike Information Criterion. RESULTS: We included 1227 patients. Median duration of follow-up was 9.2 years (IQR: 4.2-11.4). Median CD4 was 530/mm3 at 9 years. Median CD4/CD8 ratio was 0.3 (IQR: 0.2-0.5) at baseline and 0.6 (IQR: 0.4-0.9) after 9 years. Incidence of first NADE was 7.4/100 person-years, the most common being bacterial infections (21%), cardiovascular events (14%) and cancers (10%). For both bacterial infections and cardiovascular events, the CD4/CD8 ratio did not add predictive information to the CD4 cell count. However, low CD4/CD8 ratio was the best predictor of non-AIDS cancers (adjusted HR = 2.13 for CD4/CD8 < 0.5; 95% CI = 1.32-3.44). CONCLUSIONS: CD4/CD8 ratio remains < 1 in most HIV-infected patients despite long-term CD4+ cell counts restoration on ART. A CD4/CD8 ratio < 0.5 could identify patients who require a more intensive strategy of cancer prevention or screening.

No selection of CXCR4-using variants in cell reservoirs of dual-mixed HIV-infected patients on suppressive maraviroc therapy.

We used ultradeep sequencing to investigate the evolution of the frequency of CXCR4-using viruses in the peripheral blood mononuclear cells of 22 patients infected with both CCR5 and CXCR4-using viruses treated with the CCR5 antagonist maraviroc for 24 weeks and a stable antiviral therapy. The mean CXCR4-using virus frequency in peripheral blood mononuclear cells was 59% before maraviroc intensification and 52% after 24 weeks of effective treatment, indicating no selection by maraviroc.

Significant reduction in HIV virologic failure during a 15-year period in a setting with free healthcare access.

BACKGROUND: Calendar trends in virologic failure (VF) among human immunodeficiency virus (HIV)-infected patients can help to evaluate the performance of healthcare systems and the need for new antiretroviral therapy (ART). We examined the time trend in the rate of VF beyond 6 months of ART between 1997 and 2011 in France. METHODS: We included patients from the French Hospital Database on HIV who received at least 6 months of ART. VF was defined as 2 consecutive plasma HIV-RNA values >500 copies/mL or as 1 value >500 copies/mL followed by a treatment switch. We adjusted for patients' characteristics by fitting a multivariable generalized estimating equation logistic regression model with an exchangeable covariance matrix. RESULTS: A total of 81 738 patients were enrolled, and median follow-up was 112.4 months. Median CD4 count was 333 cells/µL, and 23% of patients had HIV infection classified as Centers for Disease Control and Prevention stage C. Overall, 29.3% of patients received single/dual-drug ART initially, and 45.4% of patients experienced at least 1 episode of VF during follow-up. The percentage of patients with VF fell from 61.5% in 1997-1998 to 9.7% in 2009-2011 (P < .0001). Factors associated with the lower frequency of VF were recent calendar period, a higher contemporary CD4 cell count, and first-line regimens based on nonnucleoside reverse transcriptase inhibitors or integrase inhibitors. CONCLUSIONS: The proportion of HIV-infected patients experiencing VF during routine care fell markedly between 1997 and 2009-2011, to only 9.7%. This was attributed to the advent of fully active and better-tolerated antiretroviral drugs, and to national guidelines recommending rapid management of VF after mid-2000.

CD4+ cell count recovery in naïve patients initiating cART, who achieved and maintained plasma HIV-RNA suppression.

INTRODUCTION: A key objective of combined antiretroviral therapy (cART) is to reach and maintain high CD4 cell counts to provide long-term protection against AIDS-defining opportunistic infections and malignancies, as well as other comorbidities. However, a high proportion of patients present late for care. Our objective was to assess CD4 cell count recovery up to seven years in naïve patients initiating cART with at least three drugs in usual clinical care. METHODS: From the French Hospital Database on HIV, we selected naïve individuals initiating cART from 2000 with at least two years of follow-up. Participants were further required to have achieved viral load suppression by six months after initiating cART and were censored in case of virological failure. We calculated the proportion of patients (Kaplan-Meier estimates) who achieved CD4 recovery to >500/mm(3) according to baseline CD4 cell count. RESULTS: A total of 15,025 patients were analyzed with a median follow-up on ART of 65.5 months (IQR: 42.3-96.0). At cART initiation, the median age was 38.6 years (IQR: 32.2-46.0), 9734 (64.8%) were men, median CD4 cell count was 239 (IQR: 130-336) and 2668 (17.8%) had a prior AIDS event. RESULTS are presented in the Table 1. CONCLUSIONS: This study shows that CD4 cell counts continue to increase seven years after cART initiation, whatever the baseline CD4 cell count. Failing to achieve CD4 recovery with continuous viral load suppression is rare for naïve patients initiating cART in routine clinical practice, but takes substantially longer in patients who initiate antiretroviral therapy at low CD4 cell counts.

Missed opportunities for HIV testing in newly-HIV-diagnosed patients, a cross sectional study.

BACKGROUND: In France, 1/3 HIV-infected patients is diagnosed at an advanced stage of the disease. We describe missed opportunities for earlier HIV testing in newly-HIV-diagnosed patients. METHODS: Cross sectional study. Adults living in France for ≥1 year, diagnosed with HIV-infection ≤6 months earlier, were included from 06/2009 to 10/2010. We collected information on patient characteristics at diagnosis, history of HIV testing, contacts with healthcare settings, and occurrence of HIV-related events 3 years prior to HIV diagnosis. During these 3 years, we assessed whether or not HIV testing had been proposed by the healthcare provider upon first contact in patients notifying that they were MSM or had HIV-related conditions. RESULTS: 1,008 newly HIV-diagnosed patients (mean age: 39 years; male: 79%; MSM: 53%; diagnosed with an AIDS-defining event: 16%). During the 3-year period prior to HIV diagnosis, 99% of participants had frequented a healthcare setting and 89% had seen a general practitioner at least once a year. During a contact with a healthcare setting, 91/191 MSM (48%) with no HIV-related conditions, said being MSM; 50 of these (55%) did not have any HIV test proposal. Only 21% (41/191) of overall MSM who visited a healthcare provider received a test proposal. Likewise, 299/364 patients (82%) who sought care for s had a missed opportunity for HIV testing. CONCLUSIONS: Under current screening policies, missed opportunities for HIV testing remain unacceptably high. This argues in favor of improving risk assessment, and HIV-related conditions recognition in all healthcare facilities.

Impact of immunodepression and moderate alcohol consumption on coronary and other arterial disease events in an 11-year cohort of HIV-infected patients on antiretroviral therapy.

OBJECTIVE: To investigate the relationship between response to antiretroviral therapy (ART), alcohol use and occurrence of a major coronary or other arterial disease event (CADE) in HIV-infected individuals. DESIGN: A cohort study. A Cox model was used to identify the correlates of a first occurrence of a major CADE. SETTING: The French ANRS CO8 APROCO-COPILOTE cohort was set up in 1997 to study clinical progression and patient-reported outcomes (PRO) after initiating a protease inhibitor-containing ART. Clinical data were retrieved from medical records. Self-administered questionnaires collected data on PRO and behaviours, including alcohol use. PARTICIPANTS: Metabolic data were only available for a subgroup (n=675) of the study group (n=1154). MAIN OUTCOME MEASURES: Major coronary or other arterial disease first event. RESULTS: Over the 11-year follow-up, 49 major CADE were observed, with an incidence rate (95% CI)=0.75(0.57 to 0.99) per 100 person-years. Immunodepression (CD4 cell count <200 cells/mm(3)) was associated with an increased risk of CADE (adjusted HR (95% CI)=2.52(1.15 to 5.48)) after adjustment for female gender (0.25(0.08 to 0.83)), age (1.07(1.04 to 1.10)) and smoking>20 cigarettes/day (4.19(2.17 to 8.11)). Moreover, individuals with moderate alcohol consumption (≤4(3) alcohol units (AU)/day for men(women)) had a lower risk of CADE (0.38(0.20 to 0.71)) than alcohol abstainers, although the risk for those drinking>4(3) AU/day for men(women) was not significantly different from this latter group. These associations remained valid after adjustment for metabolic disorders. No significant association with exposure to any specific antiretroviral was detected. CONCLUSIONS: In the long term, absence of immunodepression and moderate alcohol consumption remain associated with a lower risk of a major CADE. Combined interventions to reduce CADE-risk-related behaviours including adherence counselling for assuring long-term immunological response to ART in HIV-infected individuals are now a clinical and public health priority.

Human immunodeficiency virus infection and non-small cell lung cancer: survival and toxicity of antineoplastic chemotherapy in a cohort study.

OBJECTIVES: To describe factors associated with survival in human immunodeficiency virus (HIV)-infected subjects with non-small cell lung cancer (NSCLC) and analyze toxicities induced by cytotoxic chemotherapy and antiretroviral compounds. DESIGN: Retrospective analyses of HIV-infected subjects with NSCLC enrolled in the Dat'Aids cohort. A toxicity substudy included subjects treated by at least one cycle of cytotoxic chemotherapy. METHODS: Survival was analyzed using Cox models. In the toxicity substudy, factors associated with grade 4 hematological toxicity of each episode of combination of antiretroviral drugs and cytotoxic chemotherapy were analyzed using marginal logistic regression models. RESULTS: Fifty-two subjects were included in the study: 42 were men, median age was 48 years, 98% were smokers, with a median of 30 pack years, median CD4 was 300 cells/µl, and median survival time was 12 months. CD4 levels ≥200 cells/µl at NSCLC diagnosis (hazard ratio [HR] = 0.29, 95% confidence interval [CI] [0.10-0.89]), performance status less than 2 (HR = 0.32, 95% CI [0.15-0.68]) and highly active antiretroviral therapy (HR = 0.26, 95% CI [0.09-0.74]) were significantly associated with increased survival in the multivariable model. Forty subjects were included in the toxicity substudy, and 14 among 68 different combinations were complicated by a grade 4 hematological toxicity. Protease inhibitor use (odds ratio = 5.22, 95% CI [1.07-25.38]) was significantly associated with grade 4 hematological toxicity in the multivariable analyses. CONCLUSIONS: In HIV-infected patients, CD4 levels at NSCLC diagnosis may be a predictive factor of survival. Use of highly active antiretroviral therapy during NSCLC chemotherapy is warranted, but protease inhibitors should be used with caution, as they may enhance severe hematological toxicities.

Toxoplasmic encephalitis IRIS in HIV-infected patients: a case series and review of the literature.

BACKGROUND: Toxoplasmic encephalitis associated with immune reconstitution inflammatory syndrome (TE-IRIS) is rarely described. METHODS: To identify TE-IRIS cases, the authors performed a retrospective study of all HIV-infected patients diagnosed as having TE in our unit between January 2000 and June 2009, and a review of published cases. RESULTS: Three patients out of 65 toxoplasmic encephalitis (TE) cases, together with six from the literature, fulfilled the unmasking TE-IRIS definition. None fulfilled the paradoxical TE-IRIS definition. TE occurred within a median time of 48.5 days (IQ(25-75) 21-56) after starting antiretroviral therapy. Cases did not have distinctive clinical or neuroimaging features from TE occurring without immune reconstitution. However: (1) cases occurred at a median CD4 lymphocytes count of 222/µl (IQ(25-75) 160-280); (2) TE occurred in five patients who were supposed to take an effective chemoprophylaxis; (3) two patients had a brain biopsy showing an intense angiocentric inflammatory infiltrating with predominantly CD8 lymphocytes; (4) in one patient, the abnormal length of evolution under treatment might be due to the heightened immune response. CONCLUSION: Although rare, unmasking TE-IRIS exists and might occur despite effective prophylaxis and an unusually high CD4 lymphocyte count. Immune reconstitution inflammatory syndrome does not modify TE diagnosis and treatment but might extend its clinical course.

Immunogenicity and safety of an HIV-1 lipopeptide vaccine in healthy adults: a phase 2 placebo-controlled ANRS trial.

BACKGROUND: French National Agency for Research on AIDS and Viral Hepatitis's HIV-LIPO-5 vaccine includes five HIV-1 peptides, containing multiple CD8 and CD4 T-cell epitopes and coupled to a palmitoyl tail. Whether HIV-LIPO-5 immunogenicity varies with the dose is unknown. METHODS: HIV-negative volunteers were randomized to receive HIV-LIPO-5 vaccine at 50 microg/lipopeptide (N = 32), 150 microg/lipopeptide (N = 32), 500 microg/lipopeptide (N = 33) or placebo (N = 34) at weeks 0, 4, 12 and 24. HIV-1-specific CD8 (interferon-gamma ELISpot on peripheral blood mononuclear cells cultured for 12 days) and CD4 responses (peripheral blood mononuclear cell lymphoproliferation) were assessed at baseline, after each injection and at week 48. RESULTS: Local reactions were dose-dependent but no differences in systemic reactions appeared between groups. Sustained (at least on two separate occasions) CD8 response rates to at least one given HIV-1 pool were obtained in 22 of 32 (69%), 21 of 33 (64%) and 21 of 34 (62%) individuals for LIPO-5 50, 150 and 500 groups, respectively (P < or = 0.0001 for all comparisons to the placebo). Cumulative CD4 response rates were obtained in 15 of 32 (47%), 18 of 33 (55%) and 15 of 34 (44%) individuals (P < 0.0001 for all comparisons to placebo). At week 48, CD8 responses persisted in 47 of 91 (52%) HIV-LIPO-5 recipients. CONCLUSION: Doses of 50, 150 and 500 microg of French National Agency for Research on AIDS and Viral Hepatitis's HIV-LIPO-5 vaccine were able to elicit HIV-specific sustained CD8 and CD4 T-cell responses in healthy adults. Safety is good and all doses appear appropriate in further 'prime-boost' trials.

Prophylaxis of invasive aspergillosis with voriconazole or caspofungin during building work in patients with acute leukemia.

BACKGROUND: Invasive aspergillosis is a common life-threatening infection in patients with acute leukemia. The presence of building work near to hospital wards in which these patients are cared for is an important risk factor for the development of invasive aspergillosis. This study assessed the impact of voriconazole or caspofungin prophylaxis in patients undergoing induction chemotherapy for acute leukemia in a hematology unit exposed to building work. DESIGN AND METHODS: This retrospective cohort study was carried out between June 2003 and January 2006 during which building work exposed patients to a persistently increased risk of invasive aspergillosis. This study compared the cumulative incidence of invasive aspergillosis in patients who did or did not receive primary antifungal prophylaxis. The diagnosis of invasive aspergillosis was based on the European Organization for Research and Treatment of Cancer/Mycosis Study Group criteria. RESULTS: Two-hundred and fifty-seven patients (213 with acute myeloid leukemia, 44 with acute lymphocytic leukemia) were included. The mean age of the patients was 54 years and the mean duration of their neutropenia was 21 days. Eighty-eight received antifungal prophylaxis, most with voriconazole (n=74). The characteristics of the patients who did or did not receive prophylaxis were similar except that pulmonary antecedents (chronic bronchopulmonary disorders or active tobacco use) were more frequent in the prophylaxis group. Invasive aspergillosis was diagnosed in 21 patients (12%) in the non-prophylaxis group and four (4.5%) in the prophylaxis group (P=0.04). Pulmonary antecedents, neutropenia at diagnosis and acute myeloid leukemia with high-risk cytogenetics were positively correlated with invasive aspergillosis, whereas primary prophylaxis was negatively correlated. Survival was similar in both groups. No case of zygomycosis was observed. The 3-month mortality rate was 28% in patients with invasive aspergillosis. CONCLUSIONS: This study suggests that antifungal prophylaxis with voriconazole could be useful in acute leukemia patients undergoing first remission-induction chemotherapy in settings in which there is a high-risk of invasive aspergillosis.