A Randomized Placebo-Controlled Efficacy Study of a Prime Boost Therapeutic Vaccination Strategy in HIV-1-Infected Individuals: VRI02 ANRS 149 LIGHT Phase II Trial.

In this placebo-controlled phase II randomized clinical trial, 103 human immunodeficiency virus type 1 (HIV-1)-infected patients under cART (combined antiretroviral treatment) were randomized 2:1 to receive either 3 doses of DNA GTU-MultiHIV B (coding for Rev, Nef, Tat, Gag, and gp160) at week 0 (W0), W4, and W12, followed by 2 doses of LIPO-5 vaccine containing long peptides from Gag, Pol, and Nef at W20 and W24, or placebo. Analytical treatment interruption (ATI) was performed between W36 to W48. At W28, vaccinees experienced an increase in functional CD4+ T-cell responses (P < 0.001 for each cytokine compared to W0) measured, predominantly against Gag and Pol/Env, and an increase in HIV-specific CD8+ T cells producing interleukin 2 (IL-2) and tumor necrosis factor alpha (TNF-α) (P = 0.001 and 0.013, respectively), predominantly against Pol/Env and Nef. However, analysis of T-cell subsets by mass cytometry in a subpopulation showed an increase in the W28/W0 ratio for memory CD8+ T cells coexpressing exhaustion and senescence markers such as PD-1/TIGIT (P = 0.004) and CD27/CD57 (P = 0.044) in vaccinees compared to the placebo group. During ATI, all patients experienced viral rebound, with the maximum observed HIV RNA level at W42 (median, 4.63 log10 copies [cp]/ml; interquartile range [IQR], 4.00 to 5.09), without any difference between arms. No patient resumed cART for CD4 cell count drop. Globally, the vaccine strategy was safe. However, a secondary HIV transmission during ATI was observed. These data show that the prime-boost combination of DNA and LIPO-5 vaccines elicited broad and polyfunctional T cells. The contrast between the quality of immune responses and the lack of potent viral control underscores the need for combined immunomodulatory strategies. (This study has been registered at ClinicalTrials.gov under registration no. NCT01492985.)IMPORTANCE In this placebo-controlled phase II randomized clinical trial, we evaluated the safety and immunogenicity of a therapeutic prime-boost vaccine strategy using a recombinant DNA vaccine (GTU-MultiHIV B clade) followed by a boost vaccination with a lipopeptide vaccine (HIV-LIPO-5) in HIV-infected patients on combined antiretroviral therapy. We show here that this prime-boost strategy is well tolerated, consistently with previous studies in HIV-1-infected individuals and healthy volunteers who received each vaccine component individually. Compared to the placebo group, vaccinees elicited strong and polyfunctional HIV-specific CD4+ and CD8+ T-cell responses. However, these immune responses presented some qualitative defects and were not able to control viremia following antiretroviral treatment interruption, as no difference in HIV viral rebound was observed in the vaccine and placebo groups. Several lessons were learned from these results, pointing out the urgent need to combine vaccine strategies with other immune-based interventions.

Hyperthyroidism in two patients with Crohn disease and Takayasu arteritis.

Thyroid abnormalities and Takayasu arteritis (TA) have been reported separately in patients with Crohn disease (CD). We report two patients with hyperthyroidism, CD and Takayasu arteritis and discuss hypothetical mechanisms. Case 1. A thyrotoxic goiter was diagnosed in 1987 in a 34-year-old woman treated since 1969 for severe CD and TA. Iodine urinary excretion was 405 microg/mL (20-500). Anti-thyrotropin receptor (TRAK) and anti-thyroid antibodies were not detectable. The ultrasonography showed a nodule in the right lobe of the thyroid and two nodules in the left lobe. A 123I thyroid scan showed a multinodular goiter with no hot nodule. She was treated successfully with propylthiouracile until 1991, when a new episode of thyrotoxicosis led to a subtotal thyroidectomy. Case 2. Hyperthyroidism was diagnosed in February 2000 in a 49-year-old woman treated for CD and TA, both diagnosed in 1980. TRAK and anti-thyroid peroxydase antibodies were not detectable. The ultrasonography disclosed a normal thyroid volume with an inhomogeneous parenchymal structure and nodular images in both lobes. A 123I thyroid scan showed one hot nodule in the lower part of each lobe. A subtotal thyroidectomy was performed. The association of these three diseases may not be fortuitous, possibly explained by genetic predisposing factors and disease-related iodine deficiency both involving Nuclear Factor kappaB pathway.

Cerebral and spinal cord involvement resulting from invasive aspergillosis.

Although central nervous system involvement in disseminated aspergillosis is known to occur in immunocompromised patients, particularly after bone marrow transplantation, localized involvement of the spinal cord is exceedingly rare. In this report we present and illustrate detailed imaging findings of central nervous system invasion by Aspergillus fumigatus in a 30-year-old woman, with emphasis on the spinal cord involvement.

[Infection of a pneumonectomy site 16 years after intervention]. / Infection d'une cavité de pneumonectomie 16 ans après l'intervention.

BACKGROUND: Infection of the residual cavity after pneumonectomy generally occurs early after surgery. CASE REPORT: A 67-year old patient was hospitalized with fever 16 years after pneumonectomy for lung cancer. Investigations led to the diagnosis of infection of the pneumonectomy cavity. DISCUSSION: Late infection several years after pneumonectomy is exceptional and usually occurs in a setting of bacteriemia. Diagnosis is difficult due to modifications of the thoracic signs but should be entertained whenever unexplained fever or an inflammatory syndrome occurs in a pneumonectomized patient. The thoracic CT scan shows an abnormally enlarged cavity. Bacteriological examination of evacuated fluid provides the key to diagnosis. Drainage-lavage is indicated. Surgery may be needed exceptionally.

Resistant herpes simplex virus type 1 infection: an emerging concern after allogeneic stem cell transplantation.

Fourteen cases of severe acyclovir-resistant herpes simplex virus type 1 (HSV-1) infection, 7 of which showed resistance to foscarnet, were diagnosed among 196 allogeneic stem cell transplant recipients within a 29-month period. Recipients of unrelated stem cell transplants were at higher risk. All patients received foscarnet; 8 subsequently received cidofovir. Strains were initially foscarnet-resistant in 3 patients and secondarily so in 4 patients. In vitro resistance to acyclovir or foscarnet was associated with clinical failure of these drugs; however, in vitro susceptibility to foscarnet was associated with complete response in only 5 of 7 patients. No strain from any of the 7 patients was resistant in vitro to cidofovir; however, only 3 of 7 patients achieved complete response. Therefore, acyclovir- and/or foscarnet-resistant HSV-1 infections after allogeneic stem cell transplantation have become a concern; current strategies need to be reassessed and new strategies must be evaluated in this setting.

[Pheochromocytoma mimicking septic shock]. / Phéochromocytome simulant un choc septique.

A tumour arising from chromaffin cells, the pheochromocytoma may be associated or present with hypotension and result in a lethal shock. The authors report a rare case of pheochromocytoma simulating septic shock. They review the mechanisms by which hypersecretion of catecholamines may cause shock. The detection of pheochromocytoma in its atypical presentation is essential for early diagnosis and the reduction of mortality related to this condition.

[Granular-cell tumor: review of the literature apropos of a case of bronchial site]. / Tumeur à cellules granuleuses: revue de la littérature à propos d'une localisation bronchique.

Abrikossoff's tumor, also called granular cell tumor, is an uncommon condition, generally benign, which can affect every organ and specially skin and tongue. The authors report an observation of a bronchial tumor and review the literature. Possible relapse after treatment, locally or everywhere in the body, may occur as local or regional complication that may necessit heavy surgery. It appears that a benign tumor can have macroscopic and even microscopic aspect of malignancy, when real malignant tumors are extremely rare. Wide excision still remain current treatment of Abrikossoff's tumor. Endoscopic methods are an interessant and less invasive alternative to treat some deep tumors.