Plasmodium infection reduces the volume of the viral reservoir in SIV-infected rhesus macaques receiving antiretroviral therapy

Zhan, Xiao-Yong; Wang, Na; Liu, Guangjie; Qin, Limei; Xu, Wanwan; Shu, Zhao; Li, Qin; Chen, Xiaoping

doi:10.1186/s12977-014-0112-x

Cited by 9 publications

(5 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Propensity score (PS) correction method was used for controlling confounding factors, such as age, gender, ECoG score, T stage, N stage, brain metastases, first line TKIs. The survival analysis was performed using the Kaplan-Meier method with the statistical packages R (The R Foundation; http://www.r-project.org ; version 3.4.3) and Empower (R) ( www.empowerstats.com , X&Y solutions, inc. Boston, Massachusetts) [ 13 ]. Two sided p values less than 0.05 were considered statistically significant.…”

Section: Methodsmentioning

confidence: 99%

Patients harboring uncommon EGFR exon 19 deletion-insertion mutations respond well to first-generation EGFR inhibitors and osimeritinib upon acquisition of T790M

Wang

Zheng

et al. 2021

BMC Cancer

View full text Add to dashboard Cite

Background In the existing next generation sequencing (NGS) system, epidermal growth factor receptor (EGFR) exon 19 deletion-insertion (19delins) is still interpreted into the category of EGFR exon 19 deletion (19del). However, the controversy exists whether the two mutation types have the similar responses and resistant mechanisms to first-generation EGFR tyrosine kinase inhibitor (TKI) in non-small cell lung cancer (NSCLC) patients. Methods We successively and retrospectively reviewed the NGS data of 3054 patients diagnosed as advanced NSCLC from November 2017 to September 2020. Finally, 41 patients with EGFR 19delins mutation and 41 patients with EGFR 19del mutation who received first-generation EGFR TKIs as first-line therapy were included in the study. Results A total of 17 genotypes were identified in this study, including L747_P753delinsS (10/41), L747_A750delinsP (9/41), L747_T751delinsP (6/41) and E746_S752delinsV (3/41). Under the same baseline characteristics, the population of EGFR 19delins respond well to first line EGFR TKIs as well as those of EGFR 19del, with little difference in median progression-free survival (mPFS): 10.4 months vs. 13.1 months, p = 0.1076). Interestingly, patients with L747_T751delinsP seem to have a better mPFS than others (18.7 months vs. 13.1 months, p = 0.035). After the disease progression, both EGFR 19delins and EGFR 19del had similar rates of developing EGFR T790M mutation resistance (45.8% vs. 57.8%), and those receiving osimeritinib as second-line treatment obtain the similar survival benefits (mPFS: 12.0 months vs. 12.2 months (p = 0.97). Conclusions This retrospective cohort study furnish the evidence that therapeutic responses and survival of untreated NSCLC population with EGFR 19delins mutation are equal to those with common EGFR 19del mutation after administration of EGFR TKIs therapy.

show abstract

Section: Methodsmentioning

confidence: 99%

Patients harboring uncommon EGFR exon 19 deletion-insertion mutations respond well to first-generation EGFR inhibitors and osimeritinib upon acquisition of T790M

Wang

Zheng

et al. 2021

BMC Cancer

View full text Add to dashboard Cite

show abstract

“…As, upon activation, naïve T-cells (CD45RA + CD45RO − ) acquire a CD45RA − CD45RO + phenotype, the “antimemory” effect should limit immune activation (Figure 2 ) [ 46 ]. There is growing consensus that induction of apoptosis in the memory T-cell compartment might have a detrimental effect on the viral reservoir [ 47 – 49 ]. In this light, chloroquine/hydroxychloroquine should have an anti-reservoir potential.…”

Section: Mechanisms Of Action Of Chloroquinementioning

confidence: 99%

Chloroquine and beyond: exploring anti-rheumatic drugs to reduce immune hyperactivation in HIV/AIDS

Savarino

Shytaj

2015

Retrovirology

View full text Add to dashboard Cite

The restoration of the immune system prompted by antiretroviral therapy (ART) has allowed drastically reducing the mortality and morbidity of HIV infection. However, one main source of clinical concern is the persistence of immune hyperactivation in individuals under ART. Chronically enhanced levels of T-cell activation are associated with several deleterious effects which lead to faster disease progression and slower CD4+ T-cell recovery during ART. In this article, we discuss the rationale, and review the results, of the use of antimalarial quinolines, such as chloroquine and its derivative hydroxychloroquine, to counteract immune activation in HIV infection. Despite the promising results of several pilot trials, the most recent clinical data indicate that antimalarial quinolines are unlikely to exert a marked beneficial effect on immune activation. Alternative approaches will likely be required to reproducibly decrease immune activation in the setting of HIV infection. If the quinoline-based strategies should nevertheless be pursued in future studies, particular care must be devoted to the dosage selection, in order to maximize the chances to obtain effective in vivo drug concentrations.

show abstract

“…SIV infection in Chinese rhesus macaques shows many features that are similar to those of HIV infection in humans [19]. We established a Chinese rhesus macaque coinfection model to study how Pc malaria modulates the course of SIV infection under controlled experimental conditions [20]. Using a similar coinfection model, we investigated the modulatory effects of SIV infection on the course of Pc malaria.…”

Section: Introductionmentioning

confidence: 99%

SIV infection aggravates malaria in a Chinese rhesus monkey coinfection model

Liu

et al. 2019

BMC Infect Dis

Self Cite

View full text Add to dashboard Cite

BackgroundThe co-occurrence of human immunodeficiency virus (HIV) infection and malaria in humans in endemic areas raises the question of whether one of these infections affects the course of the other. Although epidemiological studies have shown the impact of HIV infection on malaria, the mechanism(s) are not yet fully understood. Using a Chinese rhesus macaque coinfection model with simian immunodeficiency virus (SIV) and Plasmodium cynomolgi (Pc) malaria, we investigated the effect of concurrent SIV infection on the course of malaria and the underlying immunological mechanism(s).MethodsWe randomly assigned ten Chinese rhesus monkeys to two groups based on body weight and age. The SIV-Pc coinfection animals (S + P group) were infected intravenously with SIVmac251 eight weeks prior to malaria infection, and the control animals (P group) were infected intravenously with only Pc-infected red blood cells. After malaria was cured with chloroquine phosphate, we also initiated a secondary malaria infection that lasted 4 weeks.We monitored body weight, body temperature and parasitemia, measured SIV viral loads, hemoglobin and neopterin, and tracked the CD4+, CD8+, and CD4+ memory subpopulations, Ki67 and apoptosis by flow cytometry. Then, we compared these parameters between the two groups.ResultsThe animals infected with SIV prior to Pc infection exhibited more severe malaria symptoms characterized by longer episodes, higher parasitemia, more severe anemia, greater body weight loss and higher body temperature than the animals infected with Pc alone. Concurrent SIV infection also impaired immune protection against the secondary Pc challenge infection. The coinfected animals showed a reduced B cell response to Pc malaria and produced lower levels of Pc-specific antibodies. In addition, compared to the animals subjected to Pc infection alone, the animals coinfected with SIV and Pc had suppressed total CD4+ T cells, CD4+CD28highCD95high central memory T cells, and CD4+CD28lowCD95− naïve T cells, which may result from the imbalanced immune activation and faster CD4+ T cell turnover in coinfected animals.ConclusionsSIV infection aggravates malaria physiologically and immunologically in Chinese rhesus monkeys. This nonhuman primate SIV and Pc malaria coinfection model might be a useful tool for investigating human HIV and malaria coinfection and developing effective therapeutics.

show abstract

Plasmodium infection reduces the volume of the viral reservoir in SIV-infected rhesus macaques receiving antiretroviral therapy

Cited by 9 publications

References 55 publications

Patients harboring uncommon EGFR exon 19 deletion-insertion mutations respond well to first-generation EGFR inhibitors and osimeritinib upon acquisition of T790M

Patients harboring uncommon EGFR exon 19 deletion-insertion mutations respond well to first-generation EGFR inhibitors and osimeritinib upon acquisition of T790M

Chloroquine and beyond: exploring anti-rheumatic drugs to reduce immune hyperactivation in HIV/AIDS

SIV infection aggravates malaria in a Chinese rhesus monkey coinfection model

Contact Info

Product

Resources

About