Dynamics of drug resistance-associated mutations in HIV-1 DNA reverse transcriptase sequence during effective ART.

Objectives: To investigate the dynamics of HIV-1 variants archived in cells harbouring drug resistance-associated mutations (DRAMs) to lamivudine/emtricitabine, etravirine and rilpivirine in patients under effective ART free from selective pressure on these DRAMs, in order to assess the possibility of recycling molecules with resistance history. Patients and methods: We studied 25 patients with at least one DRAM to lamivudine/emtricitabine, etravirine and/or rilpivirine identified on an RNA sequence in their history and with virological control for at least 5 years under a regimen excluding all drugs from the resistant class. Longitudinal ultra-deep sequencing (UDS) and Sanger sequencing of the reverse transcriptase region were performed on cell-associated HIV-1 DNA samples taken over the 5 years of follow-up. Results: Viral variants harbouring the analysed DRAMs were no longer detected by UDS over the 5 years in 72% of patients, with viruses susceptible to the molecules of interest found after 5 years in 80% of patients with UDS and in 88% of patients with Sanger. Residual viraemia with <50 copies/mL was detected in 52% of patients. The median HIV DNA level remained stable (2.4 at baseline versus 2.1 log10 copies/106 cells 5 years later). Conclusions: These results show a clear trend towards clearance of archived DRAMs to reverse transcriptase inhibitors in cell-associated HIV-1 DNA after a long period of virological control, free from therapeutic selective pressure on these DRAMs, reflecting probable residual replication in some reservoirs of the fittest viruses and leading to persistent evolution of the archived HIV-1 DNA resistance profile.

[Treatment of angiolymphoid hyperplasia with eosinophilia (ALHE) using topical tacrolimus: Two cases]. / Traitement de l'hyperplasie angiolymphoïde avec éosinophilie (HALE) par le tacrolimus topique : deux observations.

BACKGROUND: Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare disease, currently considered a benign vascular proliferation of unknown etiology, and whose treatment is still unclear and challenging. PATIENTS AND METHODS: Two women in their thirties consulted for itchy lesions of the right ear. Both presented with a reddish bleeding papulonodular infiltration of the auricle, with a nodule at the entrance to the external auditory canal in the first patient. Laboratory tests showed no abnormalities and in particular no hypereosinophilia or elevated serum immunoglobulin E. In both cases, histology of lesional skin showed vascular proliferation with thick-walled vessels lined by plump endothelial cells, protruding into the lumen, together with a mixed dermal inflammatory infiltrate consisting primarily of eosinophils and lymphocytes. A diagnosis of ALHE was made in both patients based on clinical and histological features. MRA revealed no underlying vascular malformation in both cases. Patients started treatment with 0.1% tacrolimus ointment twice daily. The pruritic sensation and bleeding had completely subsided within two weeks and the reddish infiltration and nodules had practically disappeared after two months of topical tacrolimus. Continuous application resulted in no recurrence at 6 months of follow-up. DISCUSSION: Treatment of ALHE is still poorly standardized due to doubts concerning the pathophysiology of this rare condition and the small number of available studies. Topical tacrolimus was originally developed for the treatment of moderate to severe atopic dermatitis because of its anti-inflammatory and immunomodulatory properties. Recent studies suggest that this drug may be effective in treating other forms of inflammatory dermatosis. Our two observations suggest that tacrolimus ointment also represents potentially valuable treatment in AHLE.