Pharmacologically-induced activation of replication competent proviruses from latency in the presence of antiretroviral treatment (ART) has been proposed as a step towards curing HIV-1 infection. However, until now, approaches to reverse HIV-1 latency in humans have yielded mixed results. Here, we report a proof-of-concept phase Ib/IIa trial where 6 aviremic HIV-1 infected adults received intravenous 5 mg/m2 romidepsin (Celgene) once weekly for 3 weeks while maintaining ART. Lymphocyte histone H3 acetylation, a cellular measure of the pharmacodynamic response to romidepsin, increased rapidly (maximum fold range: 3.7–7.7 relative to baseline) within the first hours following each romidepsin administration. Concurrently, HIV-1 transcription quantified as copies of cell-associated un-spliced HIV-1 RNA increased significantly from baseline during treatment (range of fold-increase: 2.4–5.0; p = 0.03). Plasma HIV-1 RNA increased from <20 copies/mL at baseline to readily quantifiable levels at multiple post-infusion time-points in 5 of 6 patients (range 46–103 copies/mL following the second infusion, p = 0.04). Importantly, romidepsin did not decrease the number of HIV-specific T cells or inhibit T cell cytokine production. Adverse events (all grade 1–2) were consistent with the known side effects of romidepsin. In conclusion, romidepsin safely induced HIV-1 transcription resulting in plasma HIV-1 RNA that was readily detected with standard commercial assays demonstrating that significant reversal of HIV-1 latency in vivo is possible without blunting T cell-mediated immune responses. These finding have major implications for future trials aiming to eradicate the HIV-1 reservoir.Trial Registrationclinicaltrials.gov NTC02092116

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Background Although persistent symptoms after Coronavirus disease 2019 (COVID-19) are emerging as a major complication to the infection, data on the diversity and duration of symptoms are needed. Methods Patients aged ≥18 years with a positive polymerase chain reaction (PCR) test for severe acute respiratory syndrome coronavirus 2 and hospitalized at the Department of Infectious Diseases, Aarhus University Hospital, Denmark, in the period March 11th to May 15th, were offered follow up after hospitalization. On admission, comprehensive symptom and medical history were collected, including demographic characteristics, duration of symptoms, comorbidities and concomitant medication. At discharge, patients were offered follow-up consultations – either by telephone or in-person visit – at 6 and 12 weeks at our Post-COVID-19 outpatient clinic to assess whether symptoms present at admission had resolved. Results During the inclusion period, 71 patients were admitted with COVID-19. Of these, 10 patients died, 3 were transferred to another region, 4 declined to participate and 5 were lost to follow-up before 12 weeks evaluation. Thus, 49 patients were included. Overall, 96% reported one or more persisting symptoms at 12 weeks follow-up. Main symptoms were fatigue, dyspnea, cough, chemosensory dysfunction, and headache. Conclusion A wide range of persistent symptoms in patients recovering from COVID-19 were present 12 weeks after hospitalization calling for larger descriptive studies and interdisciplinary research collaborations.

Pulmonary alveolar proteinosis (PAP) is a rare lung disease characterized by accumulation of a periodic acid Schiff (PAS)-positive eosinophilic material in the distal airways. For decades, the standard treatment of PAP has been whole lung lavage (WLL), where large quantities of saline are instilled into the lungs to remove the proteinaceous material. However, not all patients respond to this treatment. Thus, new treatment modalities, such as subcutaneous or inhaled granulocyte macrophage colony-stimulating factor (GM-CSF), and the CD20 antibody rituximab and plasmapheresis, have been investigated. Based on the current literature, a stepwise treatment plan is suggested starting with WLL, continuing to inhaled GM-CSF, and then to rituximab if the former treatment regimes are unsuccessful.