The antiviral drug remdesivir has been shown clinically effective for treatment of COVID-19. We here demonstrate suppressive but not curative effect of remdesivir in an immunocompromised patient. A man in his fifties treated with chemoimmunotherapy for chronic lymphocytic leukemia experienced a 9-week course of COVID-19 with high fever, and severe viral pneumonia. During two 10-day courses of remdesivir starting days 24 and 45 after fever onset, the pneumonia and spiking fevers remitted, but relapsed after discontinuation. Kinetics of temperature, C-reactive protein, and lymphocyte counts mirrored the remitting/relapsing SARS-CoV-2 infection. Combination therapy or longer treatment duration may be needed in immunocompromised patients.
Immune activation plays an important role in the pathogenesis of HIV disease. Although the causes are not fully understood, the forces that lead to immune dysfunction differ for CD4 and CD8 T cells. In this study, we report that the molecular pathways that drive immune activation during chronic HIV infection are influenced by differences in the homeostatic regulation of the CD4 and CD8 T cell pools. Proliferation of CD4 T cells is controlled more tightly by CD4 T cell numbers than is CD8 T cell proliferation. This difference reflects the importance of maintaining a polyclonal CD4 T cell pool in host surveillance. Both pools of T cells were found to be driven by viral load and its associated state of inflammation. In the setting of HIV-induced lymphopenia, naive CD4 T cells were recruited mainly into the proliferating pool in response to CD4 T cell depletion, whereas naive CD8 T cell proliferation was driven mainly by levels of HIV RNA. RNA analysis revealed increased expression of genes associated with type I IFN and common γ chain cytokine signaling in CD4 T cell subsets and only type I IFN-associated genes in CD8 T cell subsets. In vitro studies demonstrated enhanced STAT1 phosphorylation in response to IFN-α and increased expression of the IFNAR1 transcripts in naive and memory CD4 T cells compared with that observed in CD8 T cells. CD4 T cell subsets also showed enhanced STAT1 phosphorylation in response to exogenous IL-7.
The immunologic efficacy of low-dose recombinant interleukin-2 (rIL-2) administered subcutaneously (sc) once a day in combination with highly active antiretroviral therapy (HAART) was assessed in a pilot study in patients with advanced human immunodeficiency virus (HIV) disease. Twenty-five persons with =250 CD4 cells/microL and plasma HIV-1 RNA levels =500 copies/mL for >24 weeks were randomly assigned to receive sc rIL-2 (3 x 10(6) IU once a day) with their previous antiretroviral regimen (n=13) or to continue with the same treatment (n=12). The level of CD4 T cells was significantly higher in the IL-2 group at week 24 (105+/-65/microL; P<.05) but not in the control group (30+/-78/microL). Memory T cells initially contributed to the CD4 T cell increase at week 4 (P<.05). Naive T cell increases (99+/-58/microL) in the IL-2 group became statistically significant at week 24 compared with the control group (28+/-27/microL; P<.05). Subcutaneous rIL-2 once a day in combination with HAART was well tolerated and improved immunologic surface markers in patients with advanced HIV infection.
Dementia and brain atrophy are established features of a large proportion of patients with acquired immune deficiency syndrome (AIDS). To investigate a potential mechanism for atrophy in AIDS, we measured the concentration of the endogenous neurotoxin quinolinic acid in the cerebrospinal fluid of 10 patients with AIDS and found that they had 3-fold higher quinolinic acid concentrations than 9 age-matched control subjects: 53.8 +/- 10.7 pmol/ml versus 18.4 +/- 3.4 pmol/ml, respectively (p less than 0.005). It remains to be determined whether increased brain quinolinic acid concentrations are involved in the pathogenesis of the neuropathology of AIDS.
The models achieved a consistent, high level of accuracy in predicting treatment responses, which was markedly superior to that of genotypic sensitivity scores. The models are being used to power an experimental system now available via the Internet.
Combination antiretroviral therapy can suppress human immunodeficiency virus (HIV) infection but cannot completely eradicate the virus. A major obstacle in the quest for a cure is the difficulty in targeting and measuring latently infected cells. To date, a single person seems to have been cured of HIV. Hematopoietic stem cell transplantation (HSCT) preceded this cancer patient's long-term sustained HIV remission, but researchers have been unable to replicate this cure, and the mechanisms that led to HIV remission remain to be established. In February 2014, the National Institute of Allergy and Infectious Diseases sponsored a workshop that provided a venue for in-depth discussion of whether HSCT could be exploited to cure HIV in cancer patients requiring such procedures. Participants also discussed how HSCT might be applied to a broader community of HIV-infected persons in whom the risks of HSCT currently outweigh the likelihood and benefits of HIV cure.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.