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CROI: Inflammation/activation linked to diseases of organ systems (heart, kidney, liver) & death in USA and now reported as well in Africa - HIV accelerated aging will be bigger problem in undeveloped countries
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"New data presented at CROI 2010 further confirm the importance of chronic inflammation in the pathogenesis of non-AIDS complications of HIV infection, even in those successfully treated with ART. Despite some intriguing hints into the pathogenesis and treatment of chronic inflammation provided at this conference, the cause remains unclear and is likely multifactorial."
Chronic Inflammation in HIV: CROI 2010 - written by David H Shepp, MD Associate Professor of Medicine, Hofstra University School of Medicine Division of Infectious Diseases, North Shore University Hospital-Manhasset - (03/03/10)
"In aggregate, these studies provide evidence that ongoing HIV replication is unlikely to explain chronic inflammation but leave the door open to a possible benefit from intensification therapy via reduced immune activation. the link between chronic inflammation and CVD has been more thoroughly investigated, chronic inflammation appears to have an association with disease in other organ systems with overall mortality in HIV-infected persons. CRP and fibrinogen levels at baseline were strongly correlated with subsequent mortality. Baseline levels of either marker in the highest tertile were associated with about a 2.6-fold increased risk of death. The effect of elevated CRP or fibrinogen on mortality was significant across all levels of CD4, from <200 to >500. An analysis of non-AIDS mortality data from the SMART study suggested co-infection with HCV or HBV creates and especially dangerous proinflammatory state that strongly predisposes to death in the absence of continuous ART. For patients in SMART with elevated HA plus an increased level of any of the 3 biomarkers, the adjusted hazard ratio for death increased 4.4-6.1-fold compared to those with normal levels of HA and the biomarker. Gupta et al.8 reported a small pilot study to define urinary markers of kidney inflammation in patients with HIV and proteinuria but without other known conditions predisposing to proteinuria. Compared to HIV+ but non-proteinuric controls, urinary levels of two inflammatory cytokines, MCP-1 and RANTES (assessed by cytokine/creatinine ratio) were elevated. Another hypothesized cause of chronic immune activation is persistent viral coinfection, VGCV treatment suppressed CMV infection and reduced CD8+ activation markers significantly when compared to placebo. Patients who initiated ART during acute or early HIV infection in the OPTIONS study were compared to patients in the SCOPE cohort who initiated in the chronic phase when CD4 was less than 350. Arterial stiffness associated with traditional CVD risk factors and after adjustment, with a nadir CD4 <350."
CROI:Inflammation and Mortality in HIV-infected Adults: Analysis of the FRAM Study Cohort (02/25/10)
elevated levels of CRP & fibrogen (inflammation markers) were independently associated with predicting 5-year mortality regardless of degree of immunosuppression.
CROI: Rapid Progression of Atherosclerosis at the Carotid Bifurcation Is Linked to Inflammation in HIV-infected Patients - "These data strongly suggest that inflammation contributes to the higher risk of atherosclerosis noted in HIV-infected persons." - (02/22/10)
Elite controllers, without ART or viremia, have more rapid IMT progression compared to controls
CROI:Inflammation Is Associated with Endothelial Dysfunction Among Individuals with Treated and Suppressed HIV Infection - (02/26/10)
improvements in TNF-alpha, sTNFr, IL-2, IL-6, IL-8, and IL-17 in the first 12 weeks predicted better 24- and 48-week CD4 and virologic outcomes. The ACTG team concluded that assignment to immediate versus deferred antiretroviral therapy did not affect CD4 or viral load response at week 24 or 48. But they proposed that inflammation in the first 12 weeks of treatment for opportunistic diseases and bacterial infection affects 24- and 48-week CD4 and viral load--regardless of treatment assignment.
CROI: T-cell Senescence and T-cell Activation Predict Carotid Atherosclerosis in HIV-infected Women - (02/22/10)
CROI: Early Antiretrovirals in People Diagnosed With AIDS May Quell Inflammation Faster -- (02/25/10)
CROI: Risk of Non-AIDS Death in HIV/HCV-Coinfected People in SMART - - (03/01/10)
The SMART investigators proposed that, among people coinfected with HIV and a hepatitis virus, "those with impaired liver function are particularly in a pro-inflammatory state associated with excess risk of death from causes other than AIDS--and interruption of ART further exacerbates this pro-inflammatory state."
Activation of CD8 T Cells Predicts Progression of HIV Infection in Women Coinfected with Hepatitis C Virus - (02/24/10)
CROI: Non-AIDS-defining Events among HAART-treated Adults in an Urban US vs an Urban Sub-Saharan African Setting: 'high non-AIDS events rate in Africa' - (03/09/10)
CROI: In vitro Effect of CCR5 Antagonists on Innate Immune System: Maraviroc Inhibits the Migration of Neutrophils, Macrophages and Dendritic Cells - (03/05/10)
These findings suggest that MVC might have a potential role in the down-regulation of HIV-associated chronic inflammation by blocking the recirculation and trafficking of macrophages and DC.
CROI: Cell Studies Point to Antiinflammatory Activity of Maraviroc -- (02/25/10)
CROI: Plasma Levels of Soluble CD14 (activation marker) Predict Mortality in HIV Infection - (03/05/10)
we investigated the relationship of baseline biomarkers of microbial translocation with all-cause mortality. Among patients with HIV infection, greater monocyte responsiveness to LPS, exhibited by high sCD14 levels, is associated with all-cause mortality, but other biomarkers of microbial translocation are not related to all-cause mortality. Patients in the highest quartile of LPS bioactivity, with sCD14 levels >2.71x106 pg/mL, had an OR of death of 6.0 versus the lowest quartile with levels <2.01x106 pg/mL (see table).
CROI: Effect of the Intensification with a CCR5 Antagonist Maraviroc on the Decay of the HIV-1 Latent Reservoir and Residual Viremia - reduced activation - (03/04/10)
In this preliminary analysis, intensification with MVC seems to accelerate the decay of the HIV latent reservoir. Unexpectedly, an increase in RV measured by SCA and episomal 2-LTRs DNA detection has been observed. A decrease in the activation of CD4 and CD8 cells was observed at wk12 of intensification.
CROI:Correlation of Inflammatory Biomarkers with the Framingham Coronary Risk Score in Antiretroviral-naïve HIV-1 Infected Patients - (03/03/10)
Framingham coronary risk scores and biomarker concentrations correlated well in this ART-naïve, virologically suppressed ARIES study population.
CROI: Impact of CD8+ T Cell Activation on CD4+ T Cell Recovery and Mortality in HIV-infected Ugandans Initiating Antiretroviral Therapy - (03/01/10)
CROI: Valganciclovir Reduces CD8+ T Cell Activation among HIV-infected Patients with Suboptimal CD4+ T cell Recovery During Antiretroviral Therapy - (03/01/10)
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