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    • Of the patients that presented a CD dip

    2022-05-10

    Of the 11 patients that presented a CD4 dip with no cause identified other than HIV-infection, 9 had CD4 counts >200 cells/μL in the next measurement and all experienced the event during the first 24 months of follow-up. Intra-laboratory measurements and individual patient physiologic factors also influence CD4 cell counts, and probably explain the variability observed in these patients, hence the importance of considering CD4 percentage as well. Our study has several limitations. It was a retrospective study of a single medical centre. Chart reviews were only performed in those that presented a CD4 dip (although review of the remaining charts is not expected to impact the results as these patients maintained CD4 counts >200 cells/μL). No assessment was made of the patient's antiretroviral therapy or adherence; the total white blood cell count and the proportion of CD4/CD8 Pyridostatin were also not analyzed. Even so, it was a study performed in the real word context, outside of clinical trials, with a median time of follow-up over three years. The use of a CD4 count of <200 cells/μL as the Kaplan–Meier endpoint for an increase in clinical risk (opposed to an opportunistic infection) overestimates true clinical risk, as most opportunistic infections occur at much lower CD4 counts (≤100 cells/μL), particularly during viral suppression.19, 20 Reduced CD4 monitoring would allow considerable cost savings and a broad impact on HIV clinical care, with rational re-allocation of resources to areas in need. Another potential benefit would be the alleviation of patient's anxiety from fluctuations in serial CD4 counts due to laboratory and physiologic variability. However, this represents a change in the paradigm of HIV-infection monitoring that needs to be properly addressed with patients in order to reduce unnecessary concern from not knowing CD4 cell counts. Along with other published reports,12, 13, 14, 15, 16 our data strongly supports less frequent CD4 monitoring in patients with viral suppression and high CD4 counts, and suggests that viral load monitoring is sufficient in these patients. In such patients, the risk of sustained CD4 count decline to lower levels was very low. This recent evidence may inform future guidelines. Continued viral suppression could be used as an alternative surrogate marker for adequate immunologic performance.
    Introduction In 2009, Dr. Hutter reported that a Berlin patient, Mr. Timothy Brown, who suffered both HIV infection and acute myeloid leukemia, received allogeneic CCR5Δ32/Δ32 bone marrow transplantation. The individuals with CCR5Δ32/Δ32 homozygous deletion are resistant to CCR5-tropic HIV infection. The Berlin patient showed no HIV rebound 20 months after the transplantation and the ceasing of antiretroviral therapy (ART).1, 2 Most importantly, he is still healthy and no HIV rebound has occurred after 9 years of stopping the ART. Namely, he is cured, and the only cured case until now globally. Under the encouragement of success in this Berlin patient, CCR5, the main co-receptor of HIV entry into CD4+ cells, has become an important target for gene editing anti-HIV therapy.3, 4, 5, 6, 7, 8 On the other hand, as a retrovirus, HIV reversely transcribes its single-stranded RNA genome into a double-stranded DNA, which integrates into the human genome.9, 10 The integrated viral genome can either actively promote the production of new virions or remain inactive within a CD4+ population of cells. Cells harboring inactive viral genomes, known as latent viruses, are not sensitive to ART, and they become a viral reservoir capable of producing infectious virus under altered conditions. Another type of viral reservoir results from the persistent HIV replication in anatomical sites hard to reach with drugs, such as lymphoid tissue, brain, or gut.10, 11 HIV viruses still spread through cell-to-cell despite the ART. All of these viral reservoirs contribute to the viral rebound after ART stop, and these reservoirs are the major barriers to an HIV/AIDS cure. The HIV reservoirs are established during primary infection and matured in early latent infection.10, 12 CCR5-tropic viruses predominate globally, and they remain dominant throughout the asymptomatic phase of HIV infection.13, 14 Thus, CCR5-tropic viruses are a key target for downsizing the viral reservoirs and preventing further HIV replication.