Introduction
Overview
HIV Disease Progression in the Setting of HCV Co-infection
Affected organ/system | Complication | Proposed mechanism of action | References |
---|---|---|---|
Immune | ↑ HIV disease progression | ↑ CD4 and CD8 T-cell activation, leading to ↑ immune dysfunction and cytokine production, enhanced HIV and HCV production, and ↓ T-cell counts | |
HCV-induced ↑ CD4 T-cell apoptosis, leading to severe immunodeficiency | [27] | ||
HCV-induced ↓ CD4 recovery post-HAART | [28] | ||
↑Cryoglobulinemia | ↑ Cryoglobulin production by activated B cells | [53] | |
↓ CRP production in liver | Unknown | [54] | |
Liver | ↑ Steatosis | HIV-related mitochondrial translocation (↑LPS)-induced immune activation | |
↑ Fibrosis | ↑ Activation of CD4 and CD8 T cells | [26] | |
↑ Cirrhosis | ↑ Levels of cytokines (eg, IL-4, IL-5, IL-13, TGF-β, IFN-γ and TNF-α ) and chemokines (eg, IP-10 and IL-8) | ||
↑ ESLD | HIV-induced ↓ HCV-specific CD4 and CD8 T-cell responses | ||
↑ HCC | ↑ Levels of cytotoxic CD8 T cells in liver | ||
↑ Activation of HSC | |||
↑ Apoptosis of hepatocytes and HSC, mediated by TRAIL | |||
↑ Collagen synthesis by HIV-infected HSC | [43] | ||
↑ HSC production of collagen by HIV-infected Kupffer cells | [16] | ||
Insulin resistance–associated hyperinsulinemia and hyperglycemia stimulate HSC to ↑ connective tissue growth factor and extracellular matrix | |||
Liver/metabolic | Diabetes mellitus | Unknown | [68] |
Insulin resistance | Unknown | [46] | |
Cardiovascular | HIV- and HCV-associated chronic inflammation leads to endothelial dysfunction, causing ↑ sCAMS | ||
Hematologic | Thrombocytopenia | Sequestration of platelets in cirrhosis and portal hypertension | [55] |
↓ Production of thrombopoietin in advanced liver disease | [55] | ||
Kidney | Proteinuria | Unknown | [56] |
Acute interstitial nephritis | Unknown | [58] | |
Acute tubular necrosis | |||
MPGN | Stimulation of B cells to ↑cryoglobulin production and deposits in renal vessels | ||
Acute renal failure | |||
Chronic kidney disease | |||
Gastrointestinal | Mitochondrial translocation | HIV-inducted ↑gut permeability and depletion of CD4 cells from gut-associated lymphoid tissue | [16] |
Central/peripheral nervous | Neurocognitive syndromes | HIV and HCV replication in brain | [61] |
Peripheral neuropathy syndromes | HCV core protein activates glia and ↑HIV-associated neurotoxicity | [62] | |
LPS-induced monocyte activation and ↑HIV-associated dementia | [65] | ||
Bone | Osteoporosis | ↓ Bone mass in chronic liver disease | [70] |
Osteonecrosis |
HCV-Associated Liver Disease Progression in the Setting of HIV Co-infection
Pathogenesis of Liver Disease in Co-infection
New Technologies for Diagnosis and Staging of Liver Disease
Other Complications of HIV/HCV Co-infection
Other Immune Dysregulation and Hematologic Disorders
Kidney Disease
Cardiovascular Disease
Neurologic Status
Diabetes Mellitus
Bone Complications
Treatment of HIV in Co-infected Patients
Treatment of HCV in Co-infected Patients
Current Standard Therapeutic Regimen
Predictors of Treatment Response
Adverse Events Associated with Anti-HCV Therapy
HAART as HCV Therapeutic Agent
Therapy | Therapeutic effect | Reference | Adverse event | Reference |
---|---|---|---|---|
HAART | ↓ HIV replication in liver | [71] | ↑ Liver enzymes (LEE) at HAART initiation (IRD) | [93] |
↓ Proinflammatory cytokines | ↑ Hepatoxicity | |||
↓ Hepatic necroinflammatory activity | [71] | |||
↓ Liver necrosis and inflammation | [11] | |||
↓ Liver disease progression | ↑ Hepatocellular necrosis and steatosis | [13] | ||
↓ Liver mortality | [13] | |||
Protease inhibitors | ↓ HCV replication in vitro | [88] | ||
↓ Hepatotoxicity after SVR | [76] | |||
NRTI | ↑ Steatosis | [11] | ||
↑ Hepatotoxicity after SVR | [76] | |||
Efavirenz | ↓ Hepatotoxicity after SVR to IFN | [76] | ||
HAART + PegIFN + RBV | ||||
ZDV + PegIFN + RBV | ↑ Anemia | |||
PI + pegIFN + RBV | ↓ Hepatotoxicity | [76] | ||
Synergistic ↓ HCV replication in vitro | [88] | |||
NNRTI + pegIFN + RBV | ↓ Hepatotoxicity | [76] | ||
NRTI + pegIFN + RBV | ↑ Mitochondrial toxicity | |||
↑ Steatosis and fibrosis | ||||
↓ Response to anti-HCV therapies |