[Peripheral neuropathies during systemic diseases: Part II (vasculitis)]. / Neuropathies périphériques au cours des maladies de système : partie II (vascularites).

Primary systemic vasculitides, mainly of the small and medium-sized vessels, are frequently associated with peripheral neuropathies. When the disease is already known, the appearance of a neuropathy should suggest a specific injury, especially when associated with other systemic manifestations. Conversely, when neuropathy is inaugural, close collaboration between neurologists and internists is necessary to reach a diagnosis. A standardized electro-clinical investigation specifying the topography, the evolution and the mechanism of the nerve damage enables the positive diagnosis of the neuropathy. Several elements orient the etiological diagnosis and allow to eliminate the main differential diagnosis: non systemic vasculitic neuropathy. The existence of associated systemic manifestations (glomerular or vascular nephropathy, interstitial lung disease, intra-alveolar hemorrhage, ENT involvement…), biological markers (ANCA, cryoglobulinemia, rheumatoid factor), and invasive examinations allowing histological analysis (neuromuscular biopsy) are all useful tools for.

[Peripheral neuropathies during systemic diseases: Part I (connective tissue diseases and granulomatosis)]. / Neuropathies périphériques au cours des maladies de système : partie I (connectivites et granulomatoses).

Systemic diseases (connective disease, granulomatosis) may be associated with peripheral neuropathies. The diagnosis can be complex when the neuropathy is the presenting manifestation of the disease, requiring close collaboration between neurologists and internists. Conversely, when the systemic disease is already known, the main question remaining is its imputability in the neuropathy. Regardless of the situation, the positive diagnosis of neuropathy is based on a systematic and rigorous electro-clinical investigation, specifying the topography, the evolution and the mechanism of the nerve damage. Certain imaging examinations, such as nerve and/or plexus MRI, or other more invasive examinations (skin biopsy, neuromuscular biopsy) enable to specify the topography and the mechanism of the injury. The imputability of the neuropathy in the course of a known systemic disease is based mainly on its electro-clinical pattern, on which the alternatives diagnoses depend. In the case of an inaugural neuropathy, a set of arguments orients the diagnosis, including the underlying terrain (young subject), possible associated systemic manifestations (inflammatory arthralgias, polyadenopathy), results of first-line laboratory tests (lymphopenia, hyper-gammaglobulinemia, hypocomplementemia), autoantibodies (antinuclear, anti-native DNA, anti-SSA/B) and sometimes invasive examinations (neuromuscular biopsy).

Identification of early-induced broadly neutralizing activities against transmitted founder HIV strains.

OBJECTIVES: Broadly neutralizing antibodies have been proposed as key actors for HIV vaccine development. However, they display features of highly matured antibodies, hampering their induction by vaccination. As protective broadly neutralizing antibodies should be induced rapidly after vaccination and should neutralize the early-transmitted founder (T/F) viruses, we searched whether such antibodies may be induced following HIV infection. DESIGN: Sera were collected during acute infection (Day 0) and at viral set point (Month 6/12) and the neutralizing activity against T/F strains was investigated. Neutralizing activity in sera collected from chronic progressor was analyzed in parallel. METHODS: We compared neutralizing activity against T/F strains with neutralizing activity against non-T/F strains using the conventional TZM-bL neutralizing assay. RESULTS: We found neutralizing antibodies (nAbs) preferentially directed against T/F viruses in sera collected shortly after infection. This humoral response evolved by shifting to nAbs directed against non-T/F strains. CONCLUSION: Although features associated with nAbs directed against T/F viruses need further investigations, these early-induced nAbs may display lesser maturation characteristics; therefore, this might increase their interest for future vaccine designs.

Neuropathies périphériques associées aux syndromes lymphoprolifératifs : spectre clinique et démarche diagnostique.

Lymphoproliferative syndromes (multiple myeloma, Waldenström's disease, chronic lymphocytic leukemia, lymphomas) may be associated with peripheral neuropathies. The mechanism can be dysimmune, associated or not with monoclonal gammopathies; paraneoplastic; infiltrative; or more commonly, iatrogenic or due to vitamin deficiency. The diagnosis can be complex, especially when the neuropathy is the presenting manifestation, requiring a close cooperation between internists and neurologists. The positive diagnosis of the neuropathy is based on a systematic electro-clinical investigation, which specifies the topography and the mechanism of the nerve damage, sometimes reinforced by imaging examinations, in particular, nerve and/or plexus MRI. The imputability of the neuropathy to a lymphoproliferative syndrome is based on a set of arguments including the clinical context (B signs, tumour syndrome), first-line laboratory tests (hemogram, protein electrophoresis, viral serologies, complement), auto-antibodies discussed according to the neuropathy (anti-MAG, anti-gangliosides) and sometimes more invasive examinations (bone marrow or neuro-muscular biopsies).

[Characteristics of patients admitted from emergency units in 18 internal medicine departments and organisation of these departments: A cross sectional study from SNFMI (SiFMI study group) in 2015]. / Caractéristiques des patients admis en médecine interne dans 18 hôpitaux français en aval des urgences et organisation de ces services : enquête transversale de la SNFMI (groupe d'étude SiFMI) en 2015.

INTRODUCTION: Patients admitted from emergency units represent a large portion of the population in internal medicine departments. The aim of this study is to identify characteristics of patients and organization of these departments. METHODS: Between June 29th and July 26th 2015, voluntary internal medicine departments from the SiFMI group prospectively filled anonymized internet forms to collect data of each patients admitted in their ward from emergency units, during seven consecutive days. RESULTS: Three hundred and sixty-five patients from emergency departments were admitted in 18 internal medicine inpatients departments, totalling 1100 beds and 33,530 annual stays, 56% of them for emergency units inpatients. Mean age was 68 years, 54% were women, mean Charlson score was 2.6 and 44% of the patients took at least three drugs. Main causes of hospitalization were infectious (29%) and neurological (17%) diseases. Mean length of stay was 9.2 days. The medical team was composed by a median value of 4,5 [2,75-6,25] senior full-time equivalents, 86% were internists. Each department except one received residents, two third of them were from general medicine. CONCLUSION: This study highlights a high organizational variability among internal medicine departments and patients, and sets internal medicine as a specialty with a great capacity to achieve an integrative/comprehensive management of patients and to offer a comprehensive basis for physicians in training.

Factors associated with tuberculosis-associated haemophagocytic syndrome: a multicentre case-control study.

SETTING: Tuberculosis (TB) is a potential trigger of haemophagocytic syndrome (HS) but little is known about the features of TB-associated HS.OBJECTIVE: To assess the risk factors associated with HS in patients with TB.DESIGN: We performed a multicentre case-control study assessing the medical records of adult patients diagnosed with proven TB with (TB/HS+) or without (TB/HS-) associated HS.RESULTS: Twenty-one patients with TB/HS+ (24% women, median age, 37 years [IQR 30-48]) were included in the study. Eleven patients (52%) were infected with human immunodeficiency virus and seven patients (33%) were immunocompromised due to other reasons. TB was disseminated in 17 patients (81%). Compared with 50 control TB patients (TB/HS-), patients with TB/HS+ were more likely to be immunocompromised (86% vs. 18%; P < 0.001) and to present with disseminated TB (80% vs. 12%; P < 0.001). The outcome was poorer in patients with TB/HS+, with a higher admission rate to intensive care (71% vs. 0%; P < 0.001) and a higher risk of death (38% vs. 7%; P = 0.005).CONCLUSION: TB/HS+ occurred more likely in immunocompromised patients and severely impaired the prognosis of TB. Further studies are needed to devise therapeutic strategies for patients with TB/HS+.

[Association between psychiatric comorbidities and hospital length of stay in post-emergency internal medicine patients]. / Association des comorbidités psychiatriques avec la durée de séjour des patients en médecine interne d'aval des urgences.

INTRODUCTION: Patients with psychiatric disorders suffer from a higher rate of somatic disorders than those without psychiatric disorder, often inappropriately managed. Our study aimed to describe patients with psychiatric comorbidity in post-emergency internal medicine units and to compare their length of hospital stay to patients without psychiatric disease. METHODS: This French cross sectional study used the data warehouse of the greater Paris hospitals. It included, all patients hospitalized through the emergency department in 9 internal medicine departments during the year 2017. Psychiatric disorders and the burden of somatic disorders (Charlson score) were determined through diagnostic coding. Charlson score and hospital length of stay were compared between patients with and without psychiatric comorbidity. RESULTS: In total, 8981 hospital stays (8001 patients) were included, 1867 (21%) with psychiatric comorbidity. After adjusting for age, gender, hospital and main diagnosis, the Charlson score was on average 0.68 higher in the psychiatric comorbidity group (P<0.001) and the length of hospital stay was 30% higher after further adjustment on the Charlson score (P<0.001). These differences were consistent for each main diagnosis. CONCLUSION: Patients with psychiatric comorbidity are frequent in post-emergency internal medicine wards. They experience longer hospital stays, only partly related with a higher burden of somatic disorders. Special attention should be paid to this vulnerable population.

[Cervical spinal sarcoidosis mimicking compressive cervical myelopathy: Poor prognosis after surgery]. / Sarcoïdose médullaire mimant une myélopathie cervico-arthrosique : mauvais pronostic après chirurgie.

INTRODUCTION: Cervical spinal sarcoidosis can mimic compressive cervical myelopathy leading to potentially harmful surgical procedures before the diagnosis can be made. METHODS: Retrospective description of 3 patients and review of the literature. RESULTS: Twenty-seven patients (16 men/11 women), median age 58 years [range 29-74] were described. Neurosurgical procedures consisted of laminectomy (n=10), laminoplasty (n=15) and anterior discectomy (n=2). Immediately after surgery, 17 patients (63%) worsened or remained disabled. Among the 10 patients who improved, 9 worsened secondarily. The analysis of preoperative MRI showed T2 hypersignal lesions and contrast enhancement in all patients. Neurological symptoms were inaugural in 25/27 patients, and systemic involvement of the sarcoidosis was found after surgery in 15/27 patients. After surgery, all patients received corticosteroids, along with immunosuppressive therapy in 8 cases/27. After a follow-up of 24 [16-72] months; 13 patients were stabilized or worsened, 7 were partially improved. Three died of other cause. Only 5 recovered without sequelae. CONCLUSION: In patients with compressive cervical myelopathy, leptomeningeal contrast enhancement, a T2-weighted hypersignal exceeding the compression level on MRI, and the presence of extraneurological symptoms should point to inflammatory disease. These rare manifestations may be the first symptoms of sarcoidosis and should be recognized to avoid harmful surgical procedures and to provide appropriate medical treatment.

Determinants of blood telomere length in antiretroviral treatment-naïve HIV-positive participants enrolled in the NEAT 001/ANRS 143 clinical trial.

OBJECTIVES: Our aim was to investigate factors associated with baseline blood telomere length in participants enrolled in NEAT 001/ANRS 143, a randomized, open-label trial comparing ritonavir-boosted darunavir (DRV/r) plus raltegravir (RAL) with DRV/r plus tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in antiretroviral therapy (ART)-naïve HIV-positive adults. METHODS: A cross-sectional study of 201 randomly selected participants who had stored samples available was carried out. We measured telomere length (i.e. the relative telomere length, calculated as the telomere to single copy gene ratio) at baseline with monochrome quantitative multiplex polymerase chain reaction (PCR). We used multivariable predictive linear regression to calculate mean differences and 95% confidence intervals (CIs) for the association between baseline telomere length and baseline characteristics. RESULTS: The baseline characteristics of the 201 participants did not differ from those of the 805 participants in the parent trial population: 89% were male, the mean age was 39 years, 83.6% were Caucasian, 93% acquired HIV infection via sexual transmission, the mean estimated time since HIV diagnosis was 2.1 years, the mean HIV-1 RNA load was 4.7 log10 HIV-1 RNA copies/mL, the mean nadir and baseline CD4 counts were 301 and 324 cells/µL, respectively, and the mean CD4:CD8 ratio was 0.4. In the univariate analysis, shorter telomere length was associated with older age (per 10 years) (P < 0.001), HIV-1 RNA ≥ 100 000 copies/mL (P = 0.001), CD4 count < 200 cells/µL (P = 0.037), lower CD4:CD8 ratio (P = 0.018), statin treatment (P = 0.004), and current alcohol consumption (P = 0.035). In the multivariable analysis, older age (P < 0.001) and HIV RNA ≥ 100 000 copies/mL (P = 0.054) were independently associated with shorter telomere length. CONCLUSIONS: Both age and HIV RNA viral load correlated with shorter blood telomere length in untreated persons living with HIV. These results suggest that HIV infection and age have synergistic and independent impacts upon immunosenescence.

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.

Cessation of oral anticoagulants in antiphospholipid syndrome.

Objective To study the outcome of patients with antiphospholipid syndrome (APS) after oral anticoagulant treatment cessation. Methods We performed a retrospective study of patients with APS experiencing cessation of oral anticoagulant and enrolled in a French multicentre observational cohort between January 2014 and January 2016. The main outcome was the occurrence of recurrent thrombotic event after oral anticoagulation cessation. Results Forty four APS patients interrupted oral anticoagulation. The median age was 43 (27-56) years. The median duration of anticoagulation was 21 (9-118) months. Main causes of oral anticoagulant treatment cessation were switch from vitamin K antagonists to aspirin in 15 patients, prolonged disappearance of antiphospholipid antibodies in ten, bleeding complications in nine and a poor therapeutic adherence in six. Eleven (25%) patients developed a recurrent thrombotic event after oral anticoagulation cessation, including three catastrophic APS and one death due to lower limb ischemia. Antihypertensive treatment required at time of oral anticoagulants cessation seems to be an important factor associated with recurrent thrombosis after oral anticoagulant cessation (15.2% in patients with no relapse versus 45.5% in patients with recurrent thrombosis, p = 0.038). Oral anticoagulant treatment was re-started in 18 (40.9%) patients. Conclusion The risk of a new thrombotic event in APS patients who stopped their anticoagulation is high, even in those who showed a long lasting disappearance of antiphospholipid antibodies. Except for the presence of treated hypertension, this study did not find a particular clinical or biological phenotype for APS patients who relapsed after anticoagulation cessation. Any stopping of anticoagulant in such patients should be done with caution.

Progressive contraction of the latent HIV reservoir around a core of less-differentiated CD4⁺ memory T Cells.

In patients who are receiving prolonged antiretroviral treatment (ART), HIV can persist within a small pool of long-lived resting memory CD4(+) T cells infected with integrated latent virus. This latent reservoir involves distinct memory subsets. Here we provide results that suggest a progressive reduction of the size of the blood latent reservoir around a core of less-differentiated memory subsets (central memory and stem cell-like memory (TSCM) CD4(+) T cells). This process appears to be driven by the differences in initial sizes and decay rates between latently infected memory subsets. Our results also suggest an extreme stability of the TSCM sub-reservoir, the size of which is directly related to cumulative plasma virus exposure before the onset of ART, stressing the importance of early initiation of effective ART. The presence of these intrinsic dynamics within the latent reservoir may have implications for the design of optimal HIV therapeutic purging strategies.

Drift of the HIV-1 envelope glycoprotein gp120 toward increased neutralization resistance over the course of the epidemic: a comprehensive study using the most potent and broadly neutralizing monoclonal antibodies.

Extending our previous analyses to the most recently described monoclonal broadly neutralizing antibodies (bNAbs), we confirmed a drift of HIV-1 clade B variants over 2 decades toward higher resistance to bNAbs targeting almost all the identified gp120-neutralizing epitopes. In contrast, the sensitivity to bNAbs targeting the gp41 membrane-proximal external region remained stable, suggesting a selective pressure on gp120 preferentially. Despite this evolution, selected combinations of bNAbs remain capable of neutralizing efficiently most of the circulating variants.

Hemolysis and schistocytosis in the emergency department: consider pseudothrombotic microangiopathy related to vitamin B12 deficiency.

BACKGROUND: Hemolytic anemia with thrombocytopenia and schistocytosis is suggestive of thrombotic thrombocytopenic purpura (TTP). However, these features can occur in the context of vitamin B12 deficiency. AIM: To identify simple means of distinguishing between TTP and pseudothrombotic microangiopathies related to vitamin B12 deficiency (pseudo-TMA) at the bedside. DESIGN AND METHODS: Retrospective study of patients with pseudo-TMA compared with patients with TTP. The patients with pseudo-TMA were further compared with other cases of cobalamin deficiency, in order to detect factors associated with microangiopathic hemolysis during vitamin B12 deprivation. RESULTS: Seven patients with pseudo-TMA were compared with six patients with TTP. The pseudo-TMA patients had higher median lactate dehydrogenase (LDH) levels (7310 vs. 1460 IU/l, P = 0.01), a higher platelet count (73 vs.12.5 × 10(9)/l, P = 0.0023), a lower reticulocyte count (13.1 vs. 265.5 × 10(9)/l, P = 0.0012) and a lower neutrophil count (1.3 vs. 5.1 × 10(9)/l, P = 0.0023). When compared with 21 patients with vitamin B12 deficiency and anemia (but no schistocytosis), the pseudo-TMA patients were more likely to present with pernicious anemia [7 out of 21 (33.3%) vs. 5 out of 7 (71.4%), respectively] and had lower vitamin B12 levels (105 vs. 45 µmol/l, respectively). Vitamin supplementation led to hematological improvements in all pseudo-TMA patients. CONCLUSION: In a context of mechanical hemolysis with thrombocytopenia in a patient admitted to the emergency department, very high LDH levels and a low reticulocyte count are strongly suggestive of pseudo-TMA and should prompt the physician to screen for cobalamin deficiency.

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.

Effect of adherence as measured by MEMS, ritonavir boosting, and CYP3A5 genotype on atazanavir pharmacokinetics in treatment-naive HIV-infected patients.

We investigated population pharmacokinetics and pharmacogenetics of ritonavir-boosted atazanavir (ATV), using drug intake times exactly recorded by the Medication Event Monitoring System. The ANRS 134-COPHAR 3 trial was conducted in 35 HIV-infected treatment-naive patients. ATV (300 mg), ritonavir (100 mg), and tenofovir (300 mg) + emtricitabine (200 mg), in bottles with MEMS caps, were taken once daily for 6 months. Six blood samples were collected at week 4 to measure drug concentrations, and trough levels were measured bimonthly. A model integrating ATV and ritonavir pharmacokinetics and pharmacogenetics used nonlinear mixed effects. Use of exact dosing data halved unexplained variability in ATV clearance. The ritonavir-ATV interaction model suggested that optimal boosting effect is achievable at lower ritonavir exposures. Patients with at least one copy of the CYP3A5*1 allele exhibited 28% higher oral clearance. We provide evidence that variability in ATV pharmacokinetics is defined by adherence, CYP3A5 genotype, and ritonavir exposure.

Treatment of limbic encephalitis with anti-glioma-inactivated 1 (LGI1) antibodies.

We report a 72-year-old patient who developed acute limbic encephalitis initially considered of uncertain aetiology. Detailed information on clinical presentation, MRI appearance, antibody levels, cognitive impairment assessment, treatment and evolution of the patient is reported here. Since the early 2000s, many antibodies implied in central nervous system autoimmune disorders have been identified. Anti-glioma-inactivated 1 (LGI1) antibodies have been recently identified as associated with limbic encephalitis, as was the case in our patient.

Effects of recombinant human interleukin 7 on T-cell recovery and thymic output in HIV-infected patients receiving antiretroviral therapy: results of a phase I/IIa randomized, placebo-controlled, multicenter study.

BACKGROUND: The immune deficiency of human immunodeficiency virus (HIV) infection is not fully corrected with ARV therapy. Interleukin-7 (IL-7) can boost CD4 T-cell counts, but optimal dosing and mechanisms of cellular increases need to be defined. METHODS: We performed a randomized placebo-controlled dose escalation (10, 20 and 30 µg/kg) trial of 3 weekly doses of recombinant human IL-7 (rhIL-7) in ARV-treated HIV-infected persons with CD4 T-cell counts between 101 and 400 cells/µL and plasma HIV levels <50 copies/mL. Toxicity, activity and the impact of rhIL-7 on immune reconstitution were monitored. RESULTS: Doses of rhIL-7 up to 20 µg/kg were well tolerated. CD4 increases of predominantly naive and central memory T cells were brisk (averaging 323 cells/µL at 12 weeks) and durable (up to 1 year). Increased cell cycling and transient increased bcl-2 expression were noted. Expanded cells did not have the characteristics of regulatory or activated T cells. Transient low-level HIV viremia was seen in 6 of 26 treated patients; modest increases in total levels of intracellular HIV DNA were proportional to CD4 T-cell expansions. IL-7 seemed to increase thymic output and tended to improve the T-cell receptor (TCR) repertoire in persons with low TCR diversity. CONCLUSIONS: Three weekly doses of rhIL-7 at 20 µg/kg are well tolerated and lead to a dose-dependent CD4 T-cell increase and the broadening of TCR diversity in some subjects. These data suggest that this rhIL-7 dose could be advanced in future rhIL-7 clinical studies. CLINICAL TRIALS REGISTRATION: NCT0047732.

Blood Epstein-Barr virus DNA load and risk of progression to AIDS-related systemic B lymphoma.

BACKGROUND: AIDS-related lymphoma (ARL) remains the main cause of AIDS-related deaths in the combined antiretroviral therapy (cART) era. Although most ARLs are associated with the Epstein-Barr virus (EBV), whether patients with high EBV burden are more at risk of developing ARL is unknown. This study investigated the relationship between high blood EBV DNA loads and subsequent progression to ARL. METHODS: We identified 43 cases of ARL diagnosed between 1988 and 2007 within two cohorts (ANRS SEROCO/HEMOCO and PRIMO) and for which stored serum and peripheral blood mononuclear cell (PBMC) samples were available within 3 years before ARL diagnosis. For each case, two controls matched for the cohort and CD4 cell count in the year of ARL diagnosis were selected. EBV DNA was measured in PBMCs and serum samples with a commercial kit. RESULTS: High levels of EBV DNA in PBMCs collected a median of 10 months before diagnosis were associated with an increased risk of developing systemic B lymphoma (adjusted odds ratio 2.47; 95% confidence interval 1.15; 5.32 for each 1 log copies/10(6) PBMC increase in EBV load) but not with primary brain lymphoma. CONCLUSION: In this study, HIV-infected patients with undetectable EBV DNA in PBMCs did not develop ARL in the following 3 years, while high levels of EBV DNA in PBMCs predicted subsequent progression to systemic B lymphoma. Clinicians should be aware of the increased risk of developing systemic B lymphoma in HIV-infected patients with a high blood EBV DNA load.

Single-nucleotide polymorphism-defined class I and class III major histocompatibility complex genetic subregions contribute to natural long-term nonprogression in HIV infection.

We performed a genome-wide association study comparing a cohort of 144 human immunodeficiency virus (HIV type 1-infected, untreated white long-term nonprogressors (LTNPs) with a cohort of 605 HIV-1-infected white seroconverters. Forty-seven single-nucleotide polymorphisms (SNPs), located from class I to class III major histocompatibility complex (MHC) subregions, show statistical association (false discovery rate, <0.05) with the LTNP condition, among which 5 reached genome-wide significance after Bonferonni correction. The MHC LTNP-associated SNPs are ordered in ≥4 linkage disequilibrium blocks; interestingly, an MHC class III linkage disequilibrium block (defined by the rs9368699 SNP) seems specific to the LTNP phenotype.