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.

The effect of build orientation on both flexural quasi-static and fatigue behaviours of filament deposited PA6 polymer.

The present paper aims to study the effect of manufacturing build orientation on both flexural quasi-static and fatigue behaviours of semi-crystalline polyamide 6 obtained by Fused Filament Fabrication (FFF), by considering the porosity and surface roughness. The glass transition temperature, melting temperature, and crystallinity degree were measured complementary to understand better the process. Fatigue analysis is here fully described in visco-elastic domain of material. The results highlight that the XZ build orientation is better than the XY one and suggest that porosity plays an important role. The obtained results are also compared with conventional techniques given by the literature review.

Monocular blindness with preserved direct and consensual pupillary reflex in multiple sclerosis.

A 22-year-old woman with definite multiple sclerosis had right-eye blindness with preserved direct and consensual pupillary reflex to light. The anatomy of the fibers inside the optic nerve did not give a satisfactory explanation of this phenomenon. On the other hand, this case appeared to support the idea of biochemical differences between the myelin of visual pathways and that of reflex pathways. Studies are necessary to confirm this hypothesis.

[Ocular complications of porphyria. A case of Günther's disease]. / Complications oculaires des porphyries. A propos d'un cas de maladie de Günther.

On a case of Günther congenital porphyria with late ophthalmic complications, the authors study clinical and haematological manifestations of this disease (clinical signs are related to light sensibilisation: sclerodactily, hyperpigmentation, non cicatrisating wounds, long standing scars of reposed areas; they begin in the early childhood by hemolytic anemia and emission of dark port urines too). The various porphyries are then studied and their ophthalmologic signs are related either to the light sensibilisation either to angiopathy and neuropathy (acute porphyria). These are always spontaneously reversible after the acute onset; on the contrary, light sensibilisation involvements go worth and worth and in some cases (Günther disease; late cutaneous porphyria) induce irreversible damages: they begin by eyelids and conjunctival scars then involve scleral and corneal tissues (scleral malacia perforans). In fact, they have a bad prognosis: ophthalmologic surgical repair, after a little success, fails, because of the non cicatrisating tissues. Best treatment is preventive: --in case of light sensibilisation: eviction of sunlight or light sensibilisating drugs; --in case of acute porphyria: eviction of some drugs (barbiturates); surgical action.

[Puncture in retinal detachment surgery]. / La ponction au cours des interventions pour décollement de la rétine

This survey has been carried out over 186 operations for retinal detachment during which a voluntary or accidental drainage took place in 2/3 of the cases. Its frequency is studied according to the type of the detachment, its age, the duration of the preperatory rest, the number of operations and the surgical technique. The postsurgical evolution of detachments with drainage shows that the vitreous is more frequently clouded, later cleared up, and that there are more choroidal detachments and more retinal hemorrhages. The frequency of the early retinal flattening, the only one which has been studied, is not increased by drainage. It is no use debating the opportunity of drainage because indeed it is often imposed on the surgeon a as a last resort by the type of the detachment. The means for limiting its frequency are reviewed.

[Indications, technics and results of cataract surgery on an eye effected with healed or present retinal detachment or predisposed to detachment]. / Indications, techniques et résultats de la chirurgie de la cataracte sur un oeil atteint de décollement de rétine ancien ou actuel, ou prédisposé au décollement.

This communication is a survey of 53 cataract operations followed up during a period of 1-6 years, with an average of 4 years, and performed on patients who had a high risk of subsequent retinal detachment because of a preceding detachment on the fellow eye or on the cataractous eye, because of peripheral retinal degenerations, or a history of hereditary retinal detachment. Most of the operations were performed under general anesthesia and ocular hypotony. In all the cases, a limbal-based conjonctival flap with a double line of sutures (scleral and conjonctival), an iridectomy in segment, a zonulolysis and a cryoextraction, were done. As for the retina, 18 eyes received a coagulation before the cataract extraction by galvano- or cryocoagulation or even by xenon photocoagulation. Among them 3 had a detachment after the cataract extraction, but 2 of them were cured by a new operation. 15 eyes had peripheral retinal lesions which were coagulated after the cataract extraction by cryo-, laser or xenon coagulation. Nevertheless 2 had a detachment. 13 patients with a detachment on the fellow eye or in the family, had no peripheral lesion and were not coagulated. None of them had a retinal detachment after the cataract extraction. Finally the eyes operated upon a short time after the cataract extraction suffered severe complications: reopening of the cataract incision, loss of vitreous and finally loss of 2 eyes out of 3.

Immunoglobulin E in human aqueous humor and corresponding serum. A physiopathological and clinical study.

The analysis of IgE in aqueous humor yielded an average concentration of 3.4 +/- 0.97 U/ml for 22 cataract patients and 5.5 +/- 3.42 U/ml for five uveitis patients. The IgE level in aqueous humor (IgEa.h.) of the cases examined is most probably, beside hematoocular diffusion of serum IgEs, the result of intra-ocular IgE production. In comparison with (mostly normal) IgEs levels, the IgEa.h. concentration appears relatively elevated, not only with uveitis patients, but also with cataract patients, above all when lenticular opacity is accompanied by other ophthalmic diseases (glaucoma, high myopia, diabetes). This "increase" of IgEa.h. concentration in very probably due to the radioimmunosorbent (RIST) technique employed, the most sensitive method available at the time of the present study. Thus, the calculated IgEa.h. value in the cataractous eyes should be regarded simply as approximate to the normal IgEa.h. concentration. These values are of clinical significance however, since a reference IgEa.h. mean-value is indispensable to the interpretation of pathologically high IgEa.h. levels and ethics do not permit of IgEa.h. determination in healthy eyes. The mean IgEa.h. levels of the delayed-type uveitis and cataract patients examined reveal no significant differences. IgEa.h. determination could make a contribution to the etiological clarification of, for example, immediate-type uveitis cases and intra-ocular parasitosis and serve as an appropriate model to study intra-ocular immunomechanisms.