scholarly journals Dramatic HIV DNA degradation associated with spontaneous HIV suppression and disease-free outcome in a young seropositive woman following her infection

2019 ◽  
Author(s):  
Philippe Colson ◽  
Catherine Dhiver ◽  
Catherine Tamalet ◽  
Jeremy Delerce ◽  
Olga O. Glazunova ◽  
...  
Keyword(s):  
Dna Degradation ◽  
Hiv Replication ◽  
Extrinsic Factors ◽  
Stop Codons ◽  
Hiv Dna ◽  
Cell Counts ◽  
Cd4 Cell Counts ◽  
Seropositive Woman ◽  
Routine Assay

ABSTRACTStrategies to cure HIV-infected patients by virus-targeting drugs have failed to date. We identified a HIV-1-seropositive woman who spontaneously suppressed HIV replication and had normal CD4-cell counts, no HIV disease, no replication-competent virus and no cell HIV DNA detected with a routine assay. We suspected that dramatic HIV DNA degradation occurred postinfection. We performed multiple nested-PCRs followed by Sanger sequencing and applied a multiplex-PCR approach. Furthermore, we implemented a new technique based on two hybridization steps on beads prior to next-generation sequencing that removed human DNA then retrieved integrated HIV sequences with HIV-specific probes. We assembled ≈45% of the HIV genome and further analyzed the G-to-A mutations putatively generated by cellular APOBEC3 enzymes that can change tryptophan codons into stop codons. We found more G-to-A mutations in the HIV DNA from the woman than in that of her contaminator. Moreover, 74% of the tryptophan codons were changed to stop codons (25%) or were deleted as a possible consequence of gene inactivation. Finally, we found that this woman’s cells remained HIV-susceptible in vitro. Our findings show that she does not exhibit innate HIV resistance but has been cured of it by extrinsic factors, a plausible candidate for which is the gut microbiota.

scholarly journals Publisher Correction: Dramatic HIV DNA degradation associated with spontaneous HIV suppression and disease-free outcome in a young seropositive woman following her infection

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Philippe Colson ◽  
Catherine Dhiver ◽  
Catherine Tamalet ◽  
Jeremy Delerce ◽  
Olga O. Glazunova ◽  
...  
Keyword(s):  
Dna Degradation ◽  
Hiv Dna ◽  
Seropositive Woman ◽  
Disease Free

scholarly journals THE PRESENT DAY PERCEPTION OF THE PROBLEM OF IMMUNE RESTORATION OF UPON ART

2018 ◽  
Vol 10 (2) ◽  
pp. 14-27 ◽  
Author(s):  
N. A. Belyakov ◽  
T. N. Trofimova ◽  
E. V. Boeva ◽  
M. D. Semenova
Keyword(s):  
Opportunistic Infections ◽  
Blood Levels ◽  
Immune Restoration ◽  
Hiv Replication ◽  
Partial Restoration ◽  
Hiv Rna ◽  
Cell Counts ◽  
Cd4 Cell Counts ◽  
Pathogenic Factors ◽  
Cd4 Cell

Antiretroviral therapy (ART), which is intended to inhibit HIV replication, promotes partial restoration or activation of immunity. In many patients who have severe immunosuppression, ART may increase the risk of development of immune restoration syndrome (IRS), which is associated with the manifestations of opportunistic and secondary diseases that lead to worsening of the general health of patients and to their death. The present paper addresses IRS-related terminology, the risk factors of IRS development, and IRS pathogenesis, epidemiology, and clinical and laboratory manifestations. Special attention is paid to secondary and opportunistic infections associated with IRS and to the possibilities of pharmacotherapy for IRS and its complications. Characteristic radiological manifestations of brain lesions upon IRS are described as they as associated with different pathogenic factors upon initially poor immunity. It is hard to assess IRS incidence inRussia: IRS is diagnosed seldom becauseВИЧинфекция и иммуносупрессии,2018 г., Том 10, № 2 15 of the ambiguity of its clinical picture. A combination of the main clinical and laboratory manifestations of the syndrome is suggested to help in IRS diagnosis. IRS prevention is based on reasonable regiments of ART following preventing therapy for possible manifested infections and also on early ART onset upon steady CD4 cell counts and low HIV RNA blood levels.

scholarly journals Dramatic HIV DNA degradation associated with spontaneous HIV suppression and disease-free outcome in a young seropositive woman following her infection

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Philippe Colson ◽  
Catherine Dhiver ◽  
Catherine Tamalet ◽  
Jeremy Delerce ◽  
Olga O. Glazunova ◽  
...  
Keyword(s):  
Dna Degradation ◽  
Hiv Dna ◽  
Seropositive Woman ◽  
Disease Free

Human cryptosporidiosis

1996 ◽  
Vol 7 (1_suppl) ◽  
pp. 28-33 ◽  
Author(s):  
I M Hoepelman
Keyword(s):  
Immune Deficiency ◽  
Culture System ◽  
Specific Therapy ◽  
New Agents ◽  
Humoral Immune ◽  
Cell Counts ◽  
Cd4 Cell Counts ◽  
Cd4 Cell ◽  
Insight Into

Cryptosporidium parvum is a protozoan which can cause severe debilitating disease in immunocompromised individuals. Animal models have shown that cellular immunity is the most important factor against the development of the disease. Individuals with a humoral immune deficiency are also at risk. In HIV-infected patients there is a clear relationship between disease severity and CD4 cell counts. Insight into the pathogenesis and development of new agents is hampered by the lack of an in vitro culture system. Prevention is of the utmost importance due to the difficulties of therapy and the severity of the clinical disease which can develop. Oocysts are highly resistant to commonly used disinfectants. In HIV-infected patients with cryptosporidiosis, antiretroviral therapy should be instituted or modified. Moreover, non-specific therapy with antidiarrhoeal agents should also be instituted. If no effect is seen, therapy with paromomycin 500 mg 4 times daily for 2–3 weeks should be initiated, followed by maintenance therapy with 500 mg twice daily to prevent relapse.

scholarly journals Chimeric Antigen Receptor Design and Efficacy in Ovarian Cancer Treatment

2021 ◽  
Vol 22 (7) ◽  
pp. 3495
Author(s):  
Katarzyna M. Terlikowska ◽  
Bożena Dobrzycka ◽  
Sławomir J. Terlikowski
Keyword(s):  
Ovarian Cancer ◽  
In Vivo Studies ◽  
Specific Cell ◽  
Cancer Syndrome ◽  
Brca1 And Brca2 ◽  
Cell Surface Antigens ◽  
Extrinsic Factors ◽  
Molecular Therapies ◽  
Targeted Molecular Therapies

Our increased understanding of tumour biology gained over the last few years has led to the development of targeted molecular therapies, e.g., vascular endothelial growth factor A (VEGF-A) antagonists, poly[ADP-ribose] polymerase 1 (PARP1) inhibitors in hereditary breast and ovarian cancer syndrome (BRCA1 and BRCA2 mutants), increasing survival and improving the quality of life. However, the majority of ovarian cancer (OC) patients still do not have access to targeted molecular therapies that would be capable of controlling their disease, especially resistant or relapsed. Chimeric antigen receptors (CARs) are recombinant receptor constructs located on T lymphocytes or other immune cells that change its specificity and functions. Therefore, in a search for a successful solid tumour therapy using CARs the specific cell surface antigens identification is crucial. Numerous in vitro and in vivo studies, as well as studies on humans, prove that targeting overexpressed molecules, such as mucin 16 (MUC16), annexin 2 (ANXA2), receptor tyrosine-protein kinase erbB-2 (HER2/neu) causes high tumour cells toxicity and decreased tumour burden. CARs are well tolerated, side effects are minimal and they inhibit disease progression. However, as OC is heterogenic in its nature with high mutation diversity and overexpression of different receptors, there is a need to consider an individual approach to treat this type of cancer. In this publication, we would like to present the history and status of therapies involving the CAR T cells in treatment of OC tumours, suggest potential T cell-intrinsic determinants of response and resistance as well as present extrinsic factors impacting the success of this approach.

scholarly journals Risk Factors for Unfavorable Treatment Outcomes among the Human Immunodeficiency Virus-Associated Tuberculosis Population in Tashkent City, Uzbekistan: 2013–2017

2021 ◽  
Vol 18 (9) ◽  
pp. 4623
Author(s):  
Sherali Massavirov ◽  
Kristina Akopyan ◽  
Fazlkhan Abdugapparov ◽  
Ana Ciobanu ◽  
Arax Hovhanessyan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Human Immunodeficiency Virus ◽  
Treatment Outcomes ◽  
Sputum Smear ◽  
People Living With Hiv ◽  
Tb Treatment ◽  
Cell Counts ◽  
Cd4 Cell Counts ◽  
Immunodeficiency Virus ◽  
Positive Sputum Smear

Tuberculosis (TB) and human immunodeficiency virus (HIV) co-infection poses a growing clinical challenge. People living with HIV have a higher chance of developing TB, and once the disease has progressed, are at greater risk of having unfavorable TB treatment outcomes. Data on TB treatment outcomes among the HIV-associated TB population in Uzbekistan are limited. Thus, we conducted a cohort study among 808 adult patients with HIV-associated TB registered at the Tashkent TB referral hospital from 2013–2017 to document baseline characteristics and evaluate risk factors for unfavorable TB treatment outcomes. The data were collected from medical records and ambulatory cards. About 79.8% of the study population had favorable treatment outcomes. Antiretroviral therapy (ART) coverage at the admission was 26.9%. Information on CD4-cell counts and viral loads were largely missing. Having extrapulmonary TB (aOR 2.21, 95% CI: 1.38–3.53, p = 0.001), positive sputum smear laboratory results on admission (aOR 1.62, 95% CI: 1.07–2.40), diabetes (aOR 5.16, 95% CI: 1.77–14.98), and hepatitis C (aOR 1.68, 95% CI: 1.14–2.46) were independent risk factors for developing unfavorable TB treatment outcomes. The study findings provide evidence for targeted clinical management in co-infected patients with risk factors. Strengthening the integration of TB/HIV services may improve availability of key data to improve co-infection management.

scholarly journals 1250. Novel Boronic Acid Transition State Analogs (BATSI) with in vitro inhibitory activity against class A, B and C β-lactamases

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S643-S643
Author(s):  
Maria F Mojica ◽  
Christopher Bethel ◽  
Emilia Caselli ◽  
Magdalena A Taracila ◽  
Fabio Prati ◽  
...  
Keyword(s):  
Active Site ◽  
Inhibitory Activity ◽  
Covalent Bond ◽  
Thiol Group ◽  
Viable Cell ◽  
Free Thiol ◽  
Transition State Analogs ◽  
Cell Counts ◽  
Free Thiol Group

Abstract Background Catalytic mechanisms of serine β-lactamases (SBL; classes A, C and D) and metallo-β-lactamases (MBLs) have directed divergent strategies towards inhibitor design. SBL inhibitors act as high affinity substrates that -as in BATSIs- form a reversible, dative covalent bond with the conserved active site Ser. MBL inhibitors bind the active-site Zn2+ ions and displace the nucleophilic OH-. Herein, we explore the efficacy of a series of BATSI compounds with a free-thiol group at inhibiting both SBL and MBL. Methods Exploratory compounds were synthesized using stereoselective homologation of (+) pinandiol boronates to introduce the amino group on the boron-bearing carbon atom, which was subsequently acylated with mercaptopropanoic acid. Representative SBL (KPC-2, ADC-7, PDC-3 and OXA-23) and MBL (IMP-1, NDM-1 and VIM-2) were purified and used for the kinetic characterization of the BATSIs. In vitro activity was evaluated by a modified time-kill curve assay, using SBL and MBL-producing strains. Results Kinetic assays revealed that IC50 values ranged from 1.3 µM to >100 µM for this series. The best compound, s08033, demonstrated inhibitory activity against KPC-2, VIM-2, ADC-7 and PDC-3, with IC50 in the low μM range. Reduction of at least 1.5 log10-fold of viable cell counts upon exposure to sub-lethal concentrations of antibiotics (AB) + s08033, compared to the cells exposed to AB alone, demonstrated the microbiological activity of this novel compound against SBL- and MBL-producing E. coli (Table 1). Table 1 Conclusion Addition of a free-thiol group to the BATSI scaffold increases the range of these compounds resulting in a broad-spectrum inhibitor toward clinically important carbapenemases and cephalosporinases. Disclosures Robert A. Bonomo, MD, Entasis, Merck, Venatorx (Research Grant or Support)

Sign in / Sign up

Export Citation Format

Share Document