POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome is a rare variant of plasma cell dyscrasia with multiple systemic manifestations. We followed ...the progress of 20 patients with POEMS syndrome in our institution over a 10-yr period. Pulmonary hypertension (PH) was observed in five patients. All patients suffered dyspnea on exertion, which always appeared during an exacerbation of POEMS syndrome. The typical echocardiographic signs of PH were observed in all of these patients, and the median pulmonary-artery systolic pressure was 57 mm Hg (range, 50 to 65 mm Hg). Mean pulmonary-artery pressure during right side heart catheterization in two patients was 32 mm Hg. No other explanation for the PH could be found. Overproduction of cytokines was found in all cases, with high serum concentrations of interleukin-1beta, interleukin-6, tumor necrosis factor-alpha, and vascular endothelial growth factor. We suggest that PH should be added to the list of symptoms of POEMS syndrome. Cytokines may mediate POEMS syndrome-associated PH, as proposed for the other systemic manifestations of this disorder.
Intermittent interleukin-2 therapy for HIV-1 by continuous intravenous infusion leads to sustained increase of CD4 T cells. This method of administration is, however, inconvenient and has limiting ...toxic effects. We did a randomised study to compare safety and efficacy of antiviral treatment alone or combined with various interleukin-2 regimens in HIV-1-infected patients.
94 symptom-free patients, naïve to antiretroviral treatment, with CD4-T-cell counts of 250–550 cells/μL at baseline were randomly assigned zidovudine and didanosine alone (n=26) or combined with interleukin-2 administered intravenously (12 million IU/day, n=22) or subcutaneously (3 million IU/m
2
twice daily, n=24) for 5 days, or were given polyethylene-glycol-modified (PEG) interleukin-2 (2 million IU/m
2
intravenous bolus, n=22) administered every 2 months from week 2 to week 50 (seven cycles). Safety and immunological and virological results were monitored until week 56.
CD4-T-cell count increased to higher than baseline by a mean of 564 cells/μL (subcutaneous group), 676 cells/μL (intravenous group), 105 cells/μL (PEG group), and 55 cells/μL (antiretroviral-therapy group, p=0·0001). 68% and 77% of patients in the subcutaneous and intravenous groups, respectively, achieved an 80% increase of CD4 T cells (p<0·001). In these two groups, 50% of patients restored a CD4/CD8-T-cell ratio of more than 1. The groups did not differ significantly for changes in plasma HIV-1 RNA loads throughout the study. The duration of common side-effects of interleukin-2 was shorter in the subcutaneous group, which enabled outpatient treatment. Naïve and memory CD4 T cells, CD28 expression on CD4 and CD8 T cells, and restoration of in-vitro proliferative response to mitogens and recall antigens increased in the intravenous and subcutaneous groups.
Subcutaneous interleukin-2 is a convenient regimen that, as well as intravenous therapy, improves immunological function in HIV-1-infected patients receiving two nucleosides. Larger studies are needed to show whether immunological improvements translate into clinical benefit.
One likely mechanism of virological failure is poor antiretroviral drug diffusion in sites of viral replication such as the genital tract. We measured antiretroviral drug concentrations in blood and ...semen in 13 HIV-infected men failing treatment. Enfuvirtide did not cross the blood-testis barrier, whereas tenofovir accumulated in semen. Unlike indinavir, semen concentrations of lopinavir, amprenavir, saquinavir and efavirenz were ineffective. These are worrying findings, because suboptimal semen drug concentrations may enhance the risk of sexually transmitted drug-resistant HIV variants.
An ongoing outbreak of lymphogranuloma venereum (LGV) L2b proctitis, predominantly in HIV-positive men who have sex with men (MSM), has been reported in industrialised countries. A case of reactive ...arthritis after L2b proctitis is described. This case expands the spectrum of severe complications related to LGV L2b proctitis. Since this infection may be asymptomatic, this organism should be screened for in HIV-positive MSM with symptoms consistent with reactive arthritis.
Five out of 32 patients who received very early and prolonged antiretroviral therapy displayed an unusual, sustained immunovirological control after treatment discontinuation (mean duration: 77 ...months). These 'post-treatment controllers' did not have the genetic characteristics of spontaneous 'elite' controllers, although they shared very low and stable level of viral reservoir. Treatment may have dramatically decreased this reservoir and preserved potent HIV-specific immunologic responses, inducing a new balance between the virus and the host's immune system in these patients.
Disseminated Mycobacterium avium infection is a common cause of prolonged fever in advanced acquired immune-deficiency syndrome (AIDS). A profoundly immunosuppressed patient with AIDS and ...uncontrolled human immunodeficiency virus (HIV) replication presented with multiple opportunistic infections, including disseminated M. avium infection. Despite a combination of macrolide and other antimycobacterial drugs, blood cultures remained M. avium-positive during the 4 years preceding the fatal outcome. The patient was infected by the same M. avium genotype throughout the course of the disease. We report the first in vivo acquisition by M. avium of multiresistance to antimycobacterial drugs, including clarithromycin (CLM), amikacin (AM) and fluoroquinolones.
This study investigated the incidence of pancreatitis and its association with antiretroviral therapy (ART), focussing on stavudine and didanosine.
EuroSIDA has collected information on pancreatitis ...since Summer 2001. All identified cases have been verified by the coordinating centre. Individuals were followed from June 2001 or the date of entry into EuroSIDA (whichever occurred later) until a diagnosis of pancreatitis or the last study visit. Factors associated with pancreatitis were investigated using Poisson regression. Cumulative lengths of exposure to didanosine without stavudine, stavudine without didanosine, stavudine with didanosine, and other ART were time-updated variables. Treatment variables were fitted with a 6-month time lag.
There were 43 (nine presumptive) pancreatic events in 9678 individuals during 33 742 person-years (incidence 1.27/1000 person-years). The incidence among those with no, 2 or less and over 2 years' exposure to ART including stavudine and didanosine was 1.24, 1.73 and 0.78/1000 person-years, respectively. In multivariable analysis, higher baseline CD4 cell counts were associated with a decreased risk of pancreatitis. There was no evidence of an association of pancreatitis with cumulative exposure to didanosine and stavudine, didanosine without stavudine, stavudine without didanosine, or other ART.
We observed a low overall rate of pancreatitis in the years 2001-2006, and did not find an association of an increased incidence of pancreatitis with cumulative exposure to antiretroviral agents generally, and to didanosine and stavudine in particular.
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