Impact of early cART on HIV blood and semen compartments at the time of primary infection.

BACKGROUND: HIV-infected cells in semen facilitate viral transmission. We studied the establishment of HIV reservoirs in semen and blood during PHI, along with systemic immune activation and the impact of early cART. METHODS: Patients in the ANRS-147-OPTIPRIM trial received two years of early cART. Nineteen patients of the trial were analyzed, out of which 8 had acute PHI (WB ≤1 Ab). We quantified total cell-associated (ca) HIV-DNA in blood and semen and HIV-RNA in blood and semen plasma samples, collected during PHI and at 24 months of treatment. RESULTS: At enrollment, HIV-RNA load was higher in blood than in semen (median 5.66 vs 4.22 log10 cp/mL, p<0.0001). Semen HIV-RNA load correlated strongly with blood HIV-RNA load (r = 0.81, p = 0.02, the CD4 cell count (r = -0.98, p<0.0001), and the CD4/CD8 ratio (r = -0.85, p<0.01) in acute infection but not in later stages of PHI. Median blood and seminal cellular HIV-DNA levels were 3.59 and 0.31 log10cp/106 cells, respectively. HIV-DNA load peaked in semen later than in blood and then correlated with blood IP10 level (r = 0.62, p = 0.04). HIV-RNA was undetectable in blood and semen after two years of effective cART. Semen HIV-DNA load declined similarly, except in one patient who had persistently high IP-10 and IL-6 levels and used recreational drugs. CONCLUSIONS: HIV reservoir cells are found in semen during PHI, with gradual compartmentalization. Its size was linked to the plasma IP-10 level. Early treatment purges both the virus and infected cells, reducing the high risk of transmission during PHI. CLINICAL TRIALS REGISTRATION: NCT01033760.

Phase II Trial of Lenalidomide in HIV-Infected Patients with Previously Treated Kaposi's Sarcoma: Results of the ANRS 154 Lenakap Trial.

Lenalidomide, an oral immunomodulating agent, has shown promising activity in HIV-infected individuals with Kaposi's sarcoma (KS). This single-arm, multicenter, open-label, Gehan's two-stage phase II trial evaluated the efficacy and safety of lenalidomide in HIV-infected patients with progressive KS despite previous chemotherapy (NCT01282047, ANRS 154 Lenakap trial). The primary endpoint was the rate of partial response (PR) or complete response (CR) at week 24, evaluated by both the study investigators and the patients using the Physical Global Assessment (PGA). AIDS Clinical Trials Group (ACTG) criteria for KS treatment evaluation were used as a secondary endpoint. The data and safety monitoring board recommended that enrollments be halted on April 24, 2013, because of lack of responses. We enrolled 12 antiretroviral-treated HIV-infected men with progressive KS despite previous chemotherapy. Their HIV plasma viral load was <50 copies/ml and their median CD4 cell count 444/mm3. One patient stopped taking lenalidomide because of hives at week 1 and a second patient died at week 7. The remaining 10 patients were assessable at week 24, when none had PGA-defined CR or PR and one had ACTG-defined PR. There were no additional PGA responses at week 48, but an additional three patients had ACTG responses, for a total of four patients with ACTG PR at week 48 (40%; 95% confidence interval: 12.2-73.8). Fourteen grade 3-4 adverse events were considered at least possibly related to lenalidomide during a total of 101 cycles. Lenalidomide was well tolerated in antiretroviral experienced patients with progressive KS previously treated with chemotherapy. The ACTG-defined response rate at week 48 was 40%, while it was 0% using PGA criteria.

Prevalence and risk factors of sleep disturbances in a large HIV-infected adult population.

INTRODUCTION: Sleep disturbances are frequently reported in HIV-infected patients but there is a lack of large studies on prevalence and risk factors, particularly in the context of current improved immuno-clinical status and use of the newest antiretrovirals (ARV). METHOD: Cross-sectional study to evaluate the prevalence and factors associated with sleep disturbance in adult HIV-infected patients in six French centres of the region "Pays de la Loire". Patients filled a self-administered questionnaire on their health behaviour, sleep attitudes (Pittsburgh Sleep Quality Index PSQI), quality of life (WHO QOL HIV BREF questionnaire) and depression (Beck depression Inventory (BDI)-II questionnaire). Socio-demographic and immunovirologic data, medical history, ARVs were collected. RESULTS: From November 2012 to May 2013, 1354 consecutive non-selected patients were enrolled. Patients' characteristics were: 73.5% male, median age 47 years, active employment 56.7%, France-native 83% and Africa-native 14.7%, CDC stage C 21%, hepatitis co-infection 13%, lipodystrophy 11.8%, dyslipidemia 20%, high BP 15.1%, diabetes 3%, tobacco smokers 39%, marijuana and cocaine users, 11.7% and 1.7% respectively, and excessive alcohol drinkers 9%. Median (med) duration of HIV infection was 12.4 years, med CD4 count was 604/mm(3); 94% of Patients were on ARVs, 87% had undetectable viral load. Median sleeping time was 7 hours. Sleep disturbances (defined as PSQI score >5) were observed in 47% of the patients, more frequently in female (56.4%) than in male (43.9%) (p<0.05) and moderate to serious depressive symptoms (BDI score>19) in 19.7% of the patients. In multivariate analysis, factors associated with sleep disturbances (p<0.05) were depression (odds ratio [OR] 4.6; 95% confidence interval [CI] 3.2-6.8), male gender (OR 0.7; CI 0.5-0.9), active employment (OR 0.7; CI 0.5-0.9), living single (OR 1.5; CI 1.2-2.0), tobacco-smoking (OR 1.3; CI 1.0-1.8), duration of HIV infection (>10 vs. <10 y.) (OR 1.5; CI 1.1-2.0), ARV regimen containing nevirapine (OR 0.7; CI 0.5-0.9) or efavirenz (OR 0.5; CI 0.3-0.7). CONCLUSIONS: Prevalence of sleep disturbances is high in this HIV population and roughly similar to the French population. Associated factors are rather related to social and psychological status than HIV infection. Depression is frequent and should be taken in care to improve sleep quality.

Suspicion of fenofibrate-related drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome: a case report.

We describe a DRESS syndrome induced by fenofibrate. This side effect, rarely described with fenofibrate, should be known by clinicians to stop it immediately and avoid serious complications.

Mycobacterium malmoense: an underestimated nontuberculous mycobacterium.

We present a case report of Mycobacterium malmoense in a 53-year-old white man. The incidence of M. malmoense infections is a rare event compared with other nontuberculous mycobacteria, but it has increased since 1980, especially in northern Europe. Many patients have disposing underlying diseases. In most cases, it is a pulmonary infection. The most frequent used antibiotics are rifampicin (or rifabutin), ethambutol, and clarithromycin.

A case of sulphasalazine-induced DRESS syndrome with delayed acute interstitial nephritis.

Drug rash with eosinophilia and systemic symptoms (DRESS syndrome) is a rare and severe drug-induced hypersensitivity syndrome characterized by haematological abnormalities (hypereosinophilia and/or mononucleosis) and multiorgan involvement. Renal failure has been rarely described. We report the case of a 77-year-old female with sulphasalazine-induced DRESS syndrome who improved rapidly on corticosteroid treatment. After prednisone withdrawal, the patient developed renal failure that necessitated a session of haemodialysis. A kidney biopsy showed acute tubulointerstitial nephritis with an intense lymphocytic infiltrate and tubular necrosis. Kidney function normalized after a further 2 weeks of corticosteroid treatment. This is the first histologically proven case of acute tubulointerstitial nephritis in the setting of sulphasalazine-induced DRESS syndrome.

Clinical aspects and prognostic factors of leptospirosis in adults. Retrospective study in France.

BACKGROUND: Because early recognition and initiation of antibiotic therapy are important, clinicians should familiarize themselves with the clinical presentation of leptospirosis, and determine prognostic factors. PATIENTS AND METHODS: This study included all patients treated at Angers University Hospital between January 1995 and December 2005 for leptospirosis - both probable (cases combining epidemiologically suggestive features with compatible clinical, laboratory, and radiographic findings, with no other diagnosis envisioned) and confirmed (by finding microorganism on direct examination or culture of blood, urine or CSF, or by seroconversion or by a significant increase in the antibody titer between two samples). Severe leptospirosis was defined by hospitalization in the critical care department or need for renal dialysis. The statistical analysis used SPSS software version 12. RESULTS: Of 97 records reviewed, we retained 62 cases that met the criteria above, including 35 confirmed cases, 27 probable and 15 severe. The sex ratio was nine men for every woman. The patients' mean age was 45+/-18 years [12-77]. The principal clinical signs observed were: fever (n=59) with shivering (n=42), diffuse myalgia (n=41), headaches (n=38), jaundice (n=24), conjunctival suffusion (n=10), rash (n=11), herpes eruption (n=7), renal damage (n=33) that was sometimes severe (>500 micromol/L) (n=7), meningitis (n=12), meningoencephalitis (n=2), myocarditis or pericarditis (n=6), and atypical radiographic lung disease (n=16), sometimes with ARDS (n=6). Blood tests showed thrombocytopenia (platelets<140 G/L) in 65.5% of patients (n=40). Logistic regression modeling showed that two criteria remained independently predictive of development toward severe leptospirosis: clinical jaundice (p=0.005) and cardiac damage seen either clinically or on ECG (p<0.02). These factors can be identified easily at the first clinical examination and during evolution, and should help to reduce mortality by allowing earlier management of patients with suspected leptospirosis.

Use of infliximab to treat psoriatic arthritis in HIV-positive patients.

Psoriatic arthritis in HIV-positive patients is not only severe, but also raises specific treatment challenges, as immunosuppressant and immunomodulating agents may adversely affect both the course of the HIV infection and the risk of opportunistic infections. TNFalpha antagonists have not been evaluated in patients with HIV infection, which is therefore considered to contraindicate their use. Two HIV-positive patients with psoriatic arthritis unresponsive to methotrexate alone were treated with infliximab (5 and 2 mg/kg, respectively), methotrexate, and antiretroviral drugs. Dramatic improvements in the skin and joint manifestations occurred in both patients. Tolerance was good, after follow-ups of 24 and 50 months, respectively. No opportunistic infections occurred. Viral load remained well controlled and CD4+T-cell counts stable, although both patients required adjustments in their antiretroviral regimens based on close monitoring of these two parameters. HIV infection classically contraindicates the use of TNFalpha antagonists to treat refractory inflammatory joint disease. However, exceptions to this rule can be made in carefully selected patients who have exhausted all other treatment options for their joint disease and who respond well to antiretroviral therapy. Potential long-term effects such as opportunistic infections, malignancies, and loss of HIV control need to be evaluated.

Vascular thrombosis and acute cytomegalovirus infection in immunocompetent patients: report of 2 cases and literature review.

Acute cytomegalovirus (CMV) infection in immunocompetent patients is common worldwide, with seroprevalence rates of 40%-100%, depending on the country, socioeconomic conditions, and the patient's age. Infection is most often asymptomatic, but acute cytomegalovirus infection is occasionally revealed by prolonged fever, cervical lymphadenitis, and arthralgia, and it is more rarely revealed by pneumonia, myocarditis, pericarditis, colitis, and hemolytic anemia. Here, we report 2 cases of acute CMV infection in nonimmunocompromised adults that were complicated by venous thrombosis with pulmonary embolism. We also review previously reported cases of vascular thrombosis and discuss the propensity of CMV to induce vascular damage with associated thrombosis.

[Hepatosplenic localization of cat scratch disease in immunocompetent adults. Two cases]. / Localisations hépatospléniques de la maladie des griffes du chat chez l'adulte immunocompétent. Deux cas.

The infective agent responsible for cat scratch disease, Bartonella henselae, is a rare cause of hepatic granulomatosis in immunocompetent adults. Clinical features include a prolonged fever or more typical symptoms such as lymphadenopathy associated with painful hepatomegaly and a fever following a cat scratch or bite. Images of micronodular hepatosplenic lesions on abdominal ultrasonography or computed tomography scan along with epithelioid granulomas in a liver biopsy can suggest this diagnosis. It is established with a serology by indirect immunofluorescence or by ELISA and/or the presence of Bartonella henselae DNA evidenced by PCR in the liver biopsy. We report two cases of hepatosplenic localizations of cat scratch disease in a 41-year-old woman and a 44-year-old man presenting asthenia and fever associated with a biological inflammatory syndrome and elevated liver enzymes.