Long-term antiretroviral treatment initiated at primary HIV-1 infection affects the size, composition, and decay kinetics of the reservoir of HIV-1-infected CD4 T cells.

Initiation of antiretroviral therapy during the earliest stages of HIV-1 infection may limit the seeding of a long-lasting viral reservoir, but long-term effects of early antiretroviral treatment initiation remain unknown. Here, we analyzed immunological and virological characteristics of nine patients who started antiretroviral therapy at primary HIV-1 infection and remained on suppressive treatment for >10 years; patients with similar treatment duration but initiation of suppressive therapy during chronic HIV-1 infection served as controls. We observed that independently of the timing of treatment initiation, HIV-1 DNA in CD4 T cells decayed primarily during the initial 3 to 4 years of treatment. However, in patients who started antiretroviral therapy in early infection, this decay occurred faster and was more pronounced, leading to substantially lower levels of cell-associated HIV-1 DNA after long-term treatment. Despite this smaller size, the viral CD4 T cell reservoir in persons with early treatment initiation consisted more dominantly of the long-lasting central-memory and T memory stem cells. HIV-1-specific T cell responses remained continuously detectable during antiretroviral therapy, independently of the timing of treatment initiation. Together, these data suggest that early HIV-1 treatment initiation, even when continued for >10 years, is unlikely to lead to viral eradication, but the presence of low viral reservoirs and durable HIV-1 T cell responses may make such patients good candidates for future interventional studies aiming at HIV-1 eradication and cure. IMPORTANCE: Antiretroviral therapy can effectively suppress HIV-1 replication to undetectable levels; however, HIV-1 can persist despite treatment, and viral replication rapidly rebounds when treatment is discontinued. This is mainly due to the presence of latently infected CD4 T cells, which are not susceptible to antiretroviral drugs. Starting treatment in the earliest stages of HIV-1 infection can limit the number of these latently infected cells, raising the possibility that these viral reservoirs are naturally eliminated if suppressive antiretroviral treatment is continued for extremely long periods of time. Here, we analyzed nine patients who started on antiretroviral therapy within the earliest weeks of the disease and continued treatment for more than 10 years. Our data show that early treatment accelerated the decay of infected CD4 T cells and led to very low residual levels of detectable HIV-1 after long-term therapy, levels that were otherwise detectable in patients who are able to maintain a spontaneous, drug-free control of HIV-1 replication. Thus, long-term antiretroviral treatment started during early infection cannot eliminate HIV-1, but the reduced reservoirs of HIV-1 infected cells in such patients may increase their chances to respond to clinical interventions aiming at inducing a drug-free remission of HIV-1 infection.

From geriatric service to primary care: a retrospective pharmaceutical analysis of the medical prescription

Introduction The population of elderly persons is increasing andnegative outcomes due to polymedication are frequent. Discrepanciesin information about medication are frequent when older persons aretransitioning from hospital to home, increasing the risk of hospitalreadmission. The aims of this study were a) to determine discrepanciesin medical regimen indicated in two official discharge documents(DS = discharge summary, DP=discharge prescription); b) to characterizethe pharmacotherapy prescribed in older patients dischargedfrom a geriatric service.Materials & Methods Elderly patients (N=230) discharged from thegeriatric service (CHUV, Lausanne) over a 6-month period (January toJune 2009) were selected. Community pharmacists compared DS andDP to identify discrepancies including (a) drugs' name; (b) schedule ofadministration, dosage, frequency, prn prescription, treatment durationand galenic formulation. Beers' criteria were applied to identifypotentially inappropriate drugs and a descriptive analysis of drug costs,prescription profiles and generics were also performed.Results On average, patients were 82 ± 7 years old and stayed23.0 ± 11.6 days in the geriatric service. The delay between the datesof patient's discharge with the DP and the sending of the DS to hisgeneral physician averaged 14.0 ± 7.5 days (range 1-55). The DPhad an average of 10.0 ± 3.3 drugs (range 2-19). 77% of patients hadat least one discrepancy. A drug was missing on the DS in 57.8% ofpatients and 19.6% had a missing prn prescription. Among the 2312drugs prescribed, 3% belonged to Beers' list. They were prescribed to61 patients (26.5%), with 6 patients cumulating two Beers' potentiallyinappropriate drugs in their treatment. Analgesics (85% of thepatients), anticoagulants (80%), mineral supplements (77%), laxatives(52%) and antihypertensives (46%) were the drug classes most frequentlyprescribed. Mean costs of treatment as per DP was160.4 ± 179.4 Euros. Generic prescription represented more than 5%of the costs for 3 therapeutic classes (cholesterol-lowering agents(64%), antihypertensives (50%) and antidepressants (47%)).Discussion & Conclusion The high discrepancy rate between medicationlisted in the DP and the DS highlights a need for safetyimprovement. Potential benefits are expected from reinforced pharmacist-physician collaboration in transition from hospital to primarycare. In addition, even though Beers' criteria are questionable, thedrugs prescribed in this already fragile population, and the potentialopportunities of economical optimizations, are advocating thedevelopment and the scientific evaluation of a structured advancedcollaborative pharmacy practice service. This foresees improvedeffectiveness, safety and efficiency in the medication management ofelderly persons.

Primary γδ T cell lymphoma of the lung: report of a case with features suggesting derivation from intraepithelial γδ T lymphocytes [Primary gammadelta T cell lymphoma of the lung: report of a case with features suggesting derivation from intraepithelial gammadelta T lymphocytes].

T cell lymphoma of γδ T cell origin is a rare disease that mainly involves extranodal sites and shows aggressive clinical behavior. Here, we report a case of primary γδ T cell lymphoma of the lungs with epitheliotropism in the respiratory epithelium, a feature somewhat reminiscent of what is observed in enteropathy-associated T cell lymphoma. A 63-year-old man presented with chest pain and dyspnea on exertion, weight loss, and general weakness. On a positron emission tomography (PET) scan, multiple hypermetabolic lesions were found in both lungs. Microscopic examination of the wedge lung biopsy revealed nodular infiltration of monomorphic, medium- to large-sized atypical lymphocytes with round nuclei, coarse chromatin, and a variable amount of clear to eosinophilic cytoplasm. Of note, intraepithelial lymphocytosis by atypical lymphoid cells was observed in the respiratory epithelium within and around the nodule. Immunohistochemically, the tumor cells were CD3+, TCRβF1-, TCRγ+, CD5-, CD7+, CD20-, CD79a-, CD30-, CD4-, CD8-, CD10-, BCL6-, CD21-, CD56+, CD57-, and CD138-, and expressed cytotoxic molecules. Epstein-Barr virus (EBV) was not detected by an in situ hybridization assay for EBV-encoded RNA. Interestingly, CD103 was expressed by a subset of tumor cells, especially those infiltrating the epithelium. T cell clonality was detected by multiplex PCR analysis of TRG and TRD gene rearrangements. After 2 months of systemic chemotherapy, PET scan showed regression of the size and metabolic activity of the lesions. This case represents a unique γδ T cell lymphoma of the lungs showing epitheliotropism by CD103+ γδ T cells that is suggestive of tissue-resident γδ T cells as the cell of origin.

Regulation of the vitellogenin gene B1 promoter after transfer into hepatocytes in primary cultures.

The estrogen-dependent and tissue-specific regulation of the Xenopus laevis vitellogenin gene B1 promoter has been studied by lipid-mediated DNA transfer into Xenopus hepatocytes in primary culture. Hepatocytes achieve an efficient hormonal control of this promoter through a functional interaction between the estrogen responsive elements and a promoter proximal region upstream of the TATA box, which is characterized by a high density of binding sites for the transcription factors CTF/NF-1, C/EBP and HNF3. DNA accessibility to restriction enzymes within the chromosomal copy of the vitellogenin gene B1 promoter shows that the estrogen responsive unit and the promoter proximal region are sensitive to digestion in uninduced and estrogen-induced hepatocytes but not in erythrocyte nuclei. Together, these findings support the notion that chromatin configuration as well as the interplay of promoter elements mediate proper hormone-dependent and tissue-specific expression of the B1 vitellogenin gene.

Urgences vitales au cabinet médical: implications pour la formation et l'equipement du médecin de premier recours [Life-threatening emergencies at the office: implications for medical education and equipment of the primary care physician].

Every medical practitioner is confronted on a daily basis with emergencies. Among these, life-threatening emergencies can have disastrous consequences in term of morbidity and mortality; 22 cardiac arrests and 10 deaths were reported among the 1,650 Swiss practices during a 5 year period. The occurrence of life-threatening emergencies at the office necessitates, according to the type and place of the practice, the skills of the practitioner and the organization of his practice, the implementation of procedures, equipments (for example room equipped with a defibrillator, respiratory nebulizer, splints, emergency drugs) and specific continuous education programs that should be encouraged and made available to the whole medical corporation.