scholarly journals Cryptic HBV Replicative Activity Is Frequently Revealed in Anti-HBc-Positive/HBsAg-Negative Patients with HIV Infection by Highly Sensitive Molecular Assays, and Can Be Predicted by Integrating Classical and Novel Serological HBV Markers

2020 ◽  
Vol 8 (11) ◽  
pp. 1819
Author(s):  
Romina Salpini ◽  
Vincenzo Malagnino ◽  
Lorenzo Piermatteo ◽  
Tiziana Mulas ◽  
Mohammad Alkhatib ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Hiv Infection ◽  
Digital Pcr ◽  
Hbv Dna ◽  
Cd4 Cell Count ◽  
Hbv Replication ◽  
Positive Hbsag ◽  
Hbv Markers ◽  
Highly Sensitive ◽  
Combined Antiretroviral Therapy

The anti-HBc-positive/HBsAg-negative status is frequent in HIV-infection and correlates with poor survival. Here, by highly-sensitive assays, we evaluate cryptic HBV replication and factors correlated with its detection in 81 anti-HBc-positive/HBsAg-negative HIV-infected patients. Patients were treated for >12 months with HBV-active modern combined antiretroviral-therapy (cART) and had serum HBV-DNA < 20 IU/mL by commercial Real-Time PCR. Serum HBV-DNA was quantified by droplet digital PCR, serum HBV-RNA by an Abbott research assay, and anti-HBc titer (proposed to infer intrahepatic cccDNA) by Lumipulse/Fujirebio. Cryptic serum HBV-DNA was detected in 29.6% of patients (median (IQR): 4(1–15) IU/mL) and serum HBV-RNA in 3.7% of patients despite HBsAg-negativity and HBV-active cART. Notably, cryptic serum HBV-DNA correlated with an advanced CDC-stage (p = 0.01) and a lower anti-HBs titer (p = 0.05), while serum HBV-RNA correlated with lower nadir CD4+ cell-count (p = 0.01). By analyzing serological HBV-markers, the combination of anti-HBs < 50 mIU/mL (indicating lower immune response) plus anti-HBc > 15COI (reflecting higher HBV replicative activity) was predictive of cryptic serum HBV-DNA (OR: 4.7(1.1–21.7), p = 0.046, PPV = 62.5%, and NPV = 72%). In conclusion, cryptic HBV-replication (not detected by classical assays) characterizes a conspicuous set of anti-HBc-positive HIV-infected patients despite HBsAg-negativity and HBV-active combined antiretroviral therapy (cART). The integration of classical and novel markers may help identify patients with cryptic HBV-replication, thus optimizing the monitoring of anti-HBc-positive/HBsAg-negative HIV-infected patients.

scholarly journals HIV DNA Is Frequently Present within Pathologic Tissues Evaluated at Autopsy from Combined Antiretroviral Therapy-Treated Patients with Undetectable Viral Loads

2016 ◽  
Vol 90 (20) ◽  
pp. 8968-8983 ◽  
Author(s):  
Susanna L. Lamers ◽  
Rebecca Rose ◽  
Ekaterina Maidji ◽  
Melissa Agsalda-Garcia ◽  
David J. Nolan ◽  
...  
Keyword(s):  
Lymph Node ◽  
Antiretroviral Therapy ◽  
Hiv Infection ◽  
Digital Pcr ◽  
Hiv Dna ◽  
Combined Antiretroviral Therapy ◽  
Medical Histories ◽  
Autopsy Specimens ◽  
Lung Lymph ◽  
Brain Tissues

ABSTRACTHIV infection treatment strategies have historically defined effectiveness through measuring patient plasma HIV RNA. While combined antiretroviral therapy (cART) can reduce plasma viral load (pVL) to undetectable levels, the degree that HIV is eliminated from other anatomical sites remains unclear. We investigated the HIV DNA levels in 229 varied autopsy tissues from 20 HIV-positive (HIV+) cART-treated study participants with low or undetectable plasma VL and cerebrospinal fluid (CSF) VL prior to death who were enrolled in the National Neurological AIDS Bank (NNAB) longitudinal study and autopsy cohort. Extensive medical histories were obtained for each participant. Autopsy specimens, including at least six brain and nonbrain tissues per participant, were reviewed by study pathologists. HIV DNA, measured in tissues by quantitative and droplet digital PCR, was identified in 48/87 brain tissues and 82/142 nonbrain tissues at levels >200 HIV copies/million cell equivalents. No participant was found to be completely free of tissue HIV. Parallel sequencing studies from some tissues recovered intact HIV DNA and RNA. Abnormal histological findings were identified in all participants, especially in brain, spleen, lung, lymph node, liver, aorta, and kidney. All brain tissues demonstrated some degree of pathology. Ninety-five percent of participants had some degree of atherosclerosis, and 75% of participants died with cancer. This study assists in characterizing the anatomical locations of HIV, in particular, macrophage-rich tissues, such as the central nervous system (CNS) and testis. Additional studies are needed to determine if the HIV recovered from tissues promotes the pathogenesis of inflammatory diseases, such as HIV-associated neurocognitive disorders, cancer, and atherosclerosis.IMPORTANCEIt is well-known that combined antiretroviral therapy (cART) can reduce plasma HIV to undetectable levels; however, cART cannot completely clear HIV infection. An ongoing question is, “Where is HIV hiding?” A well-studied HIV reservoir is “resting” T cells, which can be isolated from blood products and succumb to cART once activated. Less-studied reservoirs are anatomical tissue samples, which have unknown cART penetration, contain a comparably diverse spectrum of potentially HIV-infected immune cells, and are important since <2% of body lymphocytes actually reside in blood. We examined 229 varied autopsy specimens from 20 HIV+participants who died while on cART and identified that >50% of tissues were HIV infected. Additionally, we identified considerable pathology in participants' tissues, especially in brain, spleen, lung, lymph node, liver, aorta, and kidney. This study substantiates that tissue-associated HIV is present despite cART and can inform future studies into HIV persistence.

scholarly journals CD4+ cell count recovery after combined antiretroviral therapy in the modern combined antiretroviral therapy era

AIDS ◽  
2018 ◽  
Vol 32 (17) ◽  
pp. 2605-2614 ◽  
Author(s):  
Hélène Roul ◽  
Murielle Mary-Krause ◽  
Jade Ghosn ◽  
Constance Delaugerre ◽  
Gilles Pialoux ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Cell Count ◽  
Cd4 Cell Count ◽  
Combined Antiretroviral Therapy ◽  
Cd4 Cell ◽  
Count Recovery

HIV Infection

2017 ◽  
Author(s):  
Meena Kannan ◽  
Harrison Taylor ◽  
William Tyor
Keyword(s):  
Nervous System ◽  
Differential Diagnosis ◽  
Antiretroviral Therapy ◽  
Hiv Infection ◽  
Clinical Management ◽  
Cytomegalovirus Infection ◽  
Clinical Presentation ◽  
Opportunistic Infections ◽  
Cryptococcal Infection ◽  
Combined Antiretroviral Therapy

This chapter focuses on four common opportunistic infections of the nervous system associated with HIV infection, namely cryptococcal infection, cytomegalovirus infection, progressive multifocal leukoencephalitis, and toxoplasmosis. Essential features of neurobiology, clinical presentation, differential diagnosis, diagnostic workup, clinical management, and outcome are discussed for each condition. Although combined antiretroviral therapy for HIV has generally reduced the incidence of these complications of HIV infection, they remain important considerations, especially in areas in which antiretrovirals are unavailable or have limited availability.

scholarly journals HIV Infection, Antiretroviral Therapy, and CD4+Cell Count Distributions in African Populations

2006 ◽  
Vol 194 (10) ◽  
pp. 1450-1458 ◽  
Author(s):  
Brian G. Williams ◽  
Eline L. Korenromp ◽  
Eleanor Gouws ◽  
George P. Schmid ◽  
Bertran Auvert ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Hiv Infection ◽  
Cell Count ◽  
Cd4 Cell Count ◽  
African Populations ◽  
Cd4 Cell

scholarly journals Survival of non-Hodgkin lymphoma patients with and without HIV infection in the era of combined antiretroviral therapy

AIDS ◽  
2010 ◽  
Vol 24 (11) ◽  
pp. 1765-1770 ◽  
Author(s):  
Chun Chao ◽  
Lanfang Xu ◽  
Donald Abrams ◽  
Wendy Leyden ◽  
Michael Horberg ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Hiv Infection ◽  
Hodgkin Lymphoma ◽  
Non Hodgkin Lymphoma ◽  
Combined Antiretroviral Therapy

scholarly journals Hepatitis B Core-Related Antigen and New Therapies for Hepatitis B

2021 ◽  
Vol 9 (10) ◽  
pp. 2083
Author(s):  
Takehisa Watanabe ◽  
Takako Inoue ◽  
Yasuhito Tanaka
Keyword(s):  
Hepatitis B ◽  
Surrogate Marker ◽  
Hbv Dna ◽  
Hbv Reactivation ◽  
New Therapies ◽  
Hbv Replication ◽  
Novel Drugs ◽  
Highly Sensitive ◽  
Risk Of Progression ◽  
Intrahepatic Hbv

The hepatitis B core-related antigen (HBcrAg) is an unprecedented novel HBV biomarker that plays an essential role in reflecting covalently closed circular DNA (cccDNA) in chronic hepatitis B (CHB) because its levels correlate with intrahepatic cccDNA and serum HBV DNA. In this review, we describe the clinical application of serum HBcrAg in CHB patients, with a particular focus on new therapies targeting intrahepatic HBV replication. (1) HBcrAg can be detected in clinical cases where serum HBV DNA is undetectable during anti-HBV therapy. (2) A highly sensitive HBcrAg assay (iTACT-HBcrAg) may be useful for monitoring HBV reactivation, as an alternative to HBV DNA. (3) Decreased HBcrAg levels have been significantly associated with promising outcomes in CHB patients, reducing the risk of progression or recurrence of hepatocellular carcinoma. Additionally, we focus on and discuss several drugs in development that target HBV replication, and monitoring HBcrAg may be useful for determining the therapeutic efficacies of such novel drugs. In conclusion, HBcrAg, especially when measured by the recently developed iTACT-HBcrAg assay, may be the most appropriate surrogate marker, over other HBV biomarkers, to predict disease progression and treatment response in CHB patients.

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