Devastating Gynecological Infections in Women with STAT3 Deficiency.

We provide the first description of a series of 9 severe gynecological infections (mastitis and pelvic cellulitis) occurring in the French national cohort of women with STAT3 deficiency. Each episode had unique features in terms of clinical presentation, microbial documentation, location, treatment duration, and related persistent esthetic damage.

Muscle Damage Due to Fusidic Acid-Statin Interaction: Review of 75 Cases From the French Pharmacovigilance Database and Literature Reports.

BACKGROUND/AREA OF UNCERTAINTY: Statins, which reduce cardiovascular risk in both primary and secondary prevention, are one of the most widely prescribed therapeutic classes in the world. Usually well-tolerated, statin-associated muscle symptoms are a well-known adverse effect. Fusidic acid (FA) is a bacteriostatic antibiotic of interest in the treatment of methicillin-resistant Staphylococcus aureus infections. Cases of rhabdomyolysis, sometimes fatal, have been reported after coprescription of FA and a statin. DATA SOURCES/AREA OF UNCERTAINTY: We studied 75 cases of muscle damage related to interaction between FA and a statin reported in the French national pharmacovigilance database (43 cases) and from a literature review (32 cases). RESULTS: Cases were mostly men (72.5%), often overweight (mean body mass index: 29.4). The most commonly reported statins were atorvastatin (60%), simvastatin (22.7%), and rosuvastatin (8.0%). Muscle disorders appeared on average 30 days after initiation of FA. Symptoms were muscle weakness (82%), dark urine (71%), and myalgia (61%). Mean creatine kinase level at diagnosis was 43,890 UI/mL, and acute renal injury occurred more than half of the cases. Outcome was fatal in 22% of cases and 28% kept sequelae at the end of the follow-up (54 days). CONCLUSIONS: Muscle damage induced by interaction between FA and statin is a potentially life-threatening complication, leading to contraindication of this association in France. This is to be reminded especially because FA is about to get FDA approval and should soon be available in the United States.

Major influence of CD4 count at the initiation of cART on viral and immunological reservoir constitution in HIV-1 infected patients.

BACKGROUND: A persistent immune activation is observed in gut during HIV-1 infection, which is not completely reversed by a combined antiretroviral therapy (cART). The impact of the time of cART initiation may highly influence the size of the viral reservoir and the ratio of CD4(+)/CD8(+) T cells in the gut. In this study, we analyzed the characteristics of HIV rectal reservoir of long-term treated patients, regarding their blood CD4(+) T cells count at the time of cART initiation. RESULTS: Twenty-four consenting men were enrolled: 9 exhibiting a CD4(+) T cells count >350/mm(3) ("high-level CD4 group") and 15 < 350/mm(3) ("low-level CD4 group") in blood, at the start of cART. An immunophenotypical analysis of T and B cells subpopulations was performed in blood and rectal biopsies. HIV cell-associated DNA loads and qualitative intra-cellular RNA were determined in both compartments. The ratio of CD4(+)/CD8(+) T cells was significantly decreased in the blood but not in the rectum of the "low-level CD4 group" of patients. The alteration in ß7(+) CD4(+) T cells homing was higher in this group and was correlated to a low ratio of CD4(+)/CD8(+) T cells in blood. An initiation of cART in men exhibiting a low-level CD4 count was also associated with an alteration of B cells maturation. HIV blood and gut DNA reservoirs were significantly lower in the "high-level CD4 group" of men. A high HIV DNA level was associated to a detectable intracellular HIV RNA in rectum. CONCLUSIONS: An early initiation of cART could significantly preserve gut immunity and limit the viral reservoir constitution.

The Genotyping Resistance Profile of the Pol Gene Detected in Blood of Newly Diagnosed HIV-Positive Men Is Durably Archived in the Gut Whatever the Time of Initiation of cART.

OBJECTIVE: To evaluate the mutational patterns on the pol gene of the main HIV-1 strain archived in cell genome of 10 chronically infected men according to their clinical and therapeutic history. The genotyping resistance profiles were compared between the first blood plasma available at the time of HIV diagnosis and rectal biopsies and PBMC sampled 1-5 years after the initiation of combined antiretroviral therapy (cART). METHODS: HIV-1 RNA and cell-associated HIV-1 DNA were quantified by Abbott Real-Time HIV-1 and Generic HIV® DNA cell (Biocentric) assays. The mutations in protease and reverse transcriptase genes were assessed by the Trugene® assay (Siemens). The C2V3 region was amplified to determine the viral tropism. RESULTS: In 9 patients, slight or no differences were observed between the 3 resistance profiles. Those mostly detected were related to the resistance to nucleos(t)ide (D67N, L210W, T215A, T69D) and nonnucleoside (K103N, V106I, V179I) inhibitors. In 1 rilpivirine-treated patient, the M230I mutation was detected in PBMC. No change of viral tropism was observed between samples. CONCLUSION: These data suggest that resistance mutations harbored by the main HIV strain in plasma at the time of diagnosis are durably archived in DNA cells whatever the delay between infection and initiation of therapy in patients well controlled by cART.

Guillain-Barré syndrome associated with Mycobacterium bovis lymphadenitis.

Guillain-Barré syndrome (GBS) is an autoimmune disease that can be triggered by different infectious agents. Here we report the case of a 26-year-old Algerian woman who developed GBS associated with a Mycobacterium bovis cervical lymphadenitis. Following intravenous immunoglobulin therapy, the patient's neurologic state returned to normal after 3 months. The lymphadenitis responded more slowly to the antituberculous treatment and an excision of necrotic cervical lymph nodes had to be performed four times. Antibiotics were administered for 16 months: ethambutol was stopped after 2 months, and rifampicin and isoniazid pursued for 14 months. An extensive etiological investigation showed that, in this case, the only likely infectious trigger GBS was the concomitant M. bovis infection. To our knowledge, this is the first report of GBS triggered by M. bovis. We performed a literature review revealing that the association between tuberculosis and Guillain-Barré syndrome is very rare (only seven cases previously reported) but is not coincidental. Physicians should be aware that tuberculosis can be a cause of GBS.

Brief Report: A High Rate of ß7+ Gut-Homing Lymphocytes in HIV-Infected Immunological Nonresponders is Associated With Poor CD4 T-Cell Recovery During Suppressive HAART.

OBJECTIVE: Correlation between GALT homing markers on lymphocytes and the low blood CD4 T-cell reconstitution in immunological nonresponders (INRs) has been studied. DESIGN: Thirty-one INRs, 19 immunological responders (IRs), and 12 noninfected controls were enrolled in this study. INRs were defined by an undetectable plasma viral load RNA less than 40 copies per milliliter and CD4 T-cell count <500 cells per cubic milliliter in at least 3 years. METHODS: A complete peripheral and mucosal lymphocyte immunophenotyping was performed on these patients with a focus on the CCR9, CCR6, and α4ß7 gut-homing markers. RESULTS: A highly significant upregulation of α4ß7 on INRs peripheral lymphocytes compared with that of IRs has been observed. This upregulation impacts different lymphocyte subsets namely CD4, CD8, and B lymphocytes. The frequency of ß7 Th17 and Treg cells are increased compared with IRs and healthy controls. The frequency of ß7 CD8 T cells in the blood is negatively correlated with integrated proviral DNA in rectal lymphoid cells in contrast to ß7 CD4 T cells associated with HIV integration. CONCLUSIONS: Alteration of lymphocyte homing abilities would have deleterious effects on GALT reconstitution and could participate to HIV reservoir constitution. These results emphasize the great interest to consider α4ß7-targeted therapy in INR patients to block homing of lymphocytes and/or to directly impair gp120-α4ß7 interactions.

[Key role played by the gut associated lymphoid tissue during human immunodeficiency virus infection]. / Infection par le virus de l'immunodéficience humaine - Rôle majeur du tissu lymphoïde de la muqueuse digestive (GALT).

The gut associated lymphoid tissue (GALT) is the site of numerous immunological disturbances during HIV-1 infection. It constitutes the largest reservoir for HIV, not or very poorly susceptible to antiretroviral therapy (ART), making it a major obstacle to HIV cure. Moreover, the GALT is involved in systemic immune activation in HIV-infected individuals: intestinal damage due to viral replication and severe CD4(+) T cell depletion in the GALT leads to microbial translocation, a key driver of immune activation, and in turn, disease progression. In this review, we describe the role of the GALT in HIV infection and we discuss therapeutic options to decrease the intestinal viral reservoir and to preserve immune function in the gut of HIV-infected people. Achieving these goals is necessary for a long-term infection control after the interruption of ART.