Is Nef the elusive cause of HIV-associated hematopoietic dysfunction?

Kirchhoff, Frank; Silvestri, Guido

doi:10.1172/jci35487

Cited by 30 publications

(41 citation statements)

References 28 publications

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“…5,6 Despite these efforts and successeses, there is still a large burden of HIV-related morbidity and mortality, notably due to complications that are not secondary to immunosuppression. 7,8 Haematological complications are reported to be among the most common nonimmunosuppressive complications of HIV. These frequently present as cytopenias, especially in ART-naive patients.…”

Section: Introductionmentioning

confidence: 99%

Cytopenias among ART-naive patients with advanced HIV disease on enrolment to care and treatment services at a tertiary hospital in Tanzania: A crosssectional study

et al. 2017

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Section: Introductionmentioning

confidence: 99%

Cytopenias among ART-naive patients with advanced HIV disease on enrolment to care and treatment services at a tertiary hospital in Tanzania: A crosssectional study

et al. 2017

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“…10 Thrombocytopenia is characterised by platelet counts below 125×10 3 /mm 3 , and also frequently occurs in HIV-infected patients. [11][12][13] Haematological parameters mainly anaemia and leukopaenia in HIV-infected ART-naïve patients result in poor ART-treatment outcome and otherwise strongly predict mortality. 2 14 15 Although haematological abnormalities are common manifestations of HIV infection and AIDS, and may have considerable impact on patients' well-being, treatment and care, few studies on haematological parameters in HIV-infected persons have been undertaken in sub-Saharan Africa.…”

Section: Introductionmentioning

confidence: 99%

Assessment of haematological parameters in HIV-infected and uninfected Rwandan women: a cross-sectional study

et al. 2012

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ObjectivesAlthough haematological abnormalities are common manifestations of HIV infection, few studies on haematological parameters in HIV-infected persons have been undertaken in sub-Saharan Africa. The authors assessed factors associated with haematological parameters in HIV-infected antiretroviral-naïve and HIV-uninfected Rwandan women.Study designCross-sectional analysis of a longitudinal cohort.SettingCommunity-based women's associations.Participants710 HIV-infected (HIV+) antiretroviral-naïve and 226 HIV-uninfected (HIV−) women from the Rwanda Women's Interassociation Study Assessment. Haematological parameters categorised as (abnormal vs normal) were compared by HIV status and among HIV+ women by CD4 count category using proportions. Multivariate logistic regression models using forward selection were fit.ResultsPrevalence of anaemia (haemoglobin (Hb) <12.0 g/dl) was higher in the HIV+ group (20.5% vs 6.3%; p<0.001), and increased with lower CD4 counts: ≥350 (7.6%), 200–349 (16%) and <200 cells/mm3 (32.2%). Marked anaemia (Hb <10.0 g/dl) was found in 4.2% of HIV+ and none of the HIV− women (p<0.001), and was highest in HIV+ women with CD4 <200 cells/mm3 (8.4%). The HIV+ were more likely than HIV− women (4.2 vs 0.5%, respectively, p=0.002) to have moderate neutropenia with white blood cells <2.0×103 cells/mm3 and 8.4% of HIV+ women with CD4 <200 cells/mm3 had moderate neutropenia. In multivariate logistic regression analysis, BMI (OR 0.87/kg/m2, 95% CI 0.82 to 0.93; p<0.001), CD4 200–350 vs HIV− (OR 3.59, 95% CI 1.89 to 6.83; p<0.001) and CD4 <200 cells/mm3 vs HIV− (OR 8.09, 95% CI 4.37 to 14.97; <0.001) had large independent associations with anaemia. There were large independent associations of CD4 <200 cells/mm3 vs HIV− (OR 7.18, 95% CI 0.78 to 65.82; p=0.081) and co-trimoxazole and/or dapsone use (OR 5.69, 95% CI 0.63 to 51.45; p=0.122) with moderate neutropenia.ConclusionsAnaemia was more common than neutropenia or thrombocytopenia in the HIV-infected Rwandan women. Future comparisons of haematological parameters in HIV-infected patients before and after antiretroviral therapy initiation are warranted.

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“…Amongst viral factors, a role for the differential activity of the NEF protein between SIVmac and SIVsm strains has been suggested[7]. NEF derived from SIVmac strains cannot downregulate CD3 on T cells as efficiently as viruses from natural hosts, which may protect infected cells from TCR-mediated activation[8].…”

Section: Introductionmentioning

confidence: 99%

Systems biology of natural simian immunodeficiency virus infections

Bosinger¹,

Jacquelin²,

Benecke³

et al. 2012

Current Opinion in HIV and AIDS

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Purpose of review A key factor driving AIDS-associated immunopathogenesis is chronic immune activation. SIV infection of African natural host species leads to high viremia, but low immune activation and absence of disease. Considerable progress in our understanding of pathological immune activation have come from comparative studies of SIV infection in pathogenic Asian macaque species and natural hosts. The focus of this review is to highlight recent work on the natural host model using high throughput genomics. Recent findings Several groups have independently conducted microarray gene expression profiling comparing in vivo SIV infection in natural and non-natural hosts. A consistent finding between these studies is that both pathogenic SIV infection of macaques and nonpathogenic infections of natural hosts have strong induction of interferon-stimulated genes (ISGs) early on, but a key difference was that natural hosts downmodulated the interferon response rapidly after acute infection. The development of new genome-based resources for further study of the natural host model is discussed. Summary Initial efforts using high throughput biology to study SIV infection of natural hosts have effectively identified the ability of natural hosts to resolve interferon responses and immune activation. Further application of ‘omic’-based technologies coupled with integrative systems-based analysis should continue to yield progress.

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Is Nef the elusive cause of HIV-associated hematopoietic dysfunction?

Cited by 30 publications

References 28 publications

Cytopenias among ART-naive patients with advanced HIV disease on enrolment to care and treatment services at a tertiary hospital in Tanzania: A crosssectional study

Cytopenias among ART-naive patients with advanced HIV disease on enrolment to care and treatment services at a tertiary hospital in Tanzania: A crosssectional study

Assessment of haematological parameters in HIV-infected and uninfected Rwandan women: a cross-sectional study

Systems biology of natural simian immunodeficiency virus infections

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