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A Tale of HCV and HIV

July 26, 2018

In 2015, I wrote a book about living with HIV, TB, and diabetes. Here, I provide some background on the human immunodeficiency and hepatitis C viruses and why they still matter.

Hepatitis C virus (HCV)

 

The 1980s saw the shaping of research to combat two viral killers. A distant cousin of the Zika virus, unknown at the time, was causing a severe form of hepatitis. Untreated inflammation of the body’s largest organ – one that helps the body digest food, store energy, and remove poisons – amounted to a death sentence in slow motion. Puzzled researchers tried to identify the pathogen that differed in how it spread and made people sick from the more commonly known, treatable hepatitis A and B viruses. Finally, in 1989, scientists at the NIH, CDC, and in industry, identified the culprit – hepatitis C, a small (55–65 nm in size), enveloped, positive-sense single-stranded RNA virus, belonging to the same family as the Zika virus (Flaviviridae). Total global HCV prevalence is estimated at 2.5% (177.5 million of HCV infected adults).[1] In the United States alone, baby boomers (1945 – 1965) are five times more likely to have HCV than other adults.[2]

 

Untreated, chronic HCV can lead to a serious life-threatening liver disease, Liver-related illnesses and deaths from HCV are on the rise. It is well-known that having HCV raises the risk for liver cancer. Interestingly, a 2015 study showed that people with HCV were also at higher risk for non-liver cancers, including non-Hodgkin lymphoma and prostate and renal cancers.[3]
•    Untreated, chronic HCV can also lead to deaths in HIV-1-infected patients managed with anti-retroviral therapy [4]

 

Human immunodeficiency virus (HIV)

 

While the most common bloodborne pathogen in the United States, HCV, lurked beneath the radar – partly because of its ability to evade the innate immune response and to defeat the adaptive immune response by mutation and functional inactivation – another virus was grabbing the headlines.[5] A killer virus was decimating predominantly gay men and hemophiliacs. People were so afraid of the disease that doctors in major medical journals debated whether they had a moral obligation to treat acquired immunodeficiency syndrome (AIDS). 


The path from a fatal disease to a chronic, treatable condition was paved with the dedication of activists and researchers. French virologists, Françoise Barré-Sinoussi and Luc Montagnier, were the co-recipients of the 2008 Nobel Prize in Physiology and Medicine for isolating a new human retrovirus (HIV-1) from a patient with lymphadenopathy. Retroviruses produce DNA from RNA, while most cells do exactly the opposite i.e. transcribe DNA into RNA. 


HIV consists of two identical single-stranded RNA molecules enclosed within a virus particle. It can be further stratified into the predominant HIV-1 virus and the less common HIV-2 virus (see Figure). Like its non-human cousin and possible ancestor, simian immunodeficiency virus (SIV), HIV can be grouped into grouped to the genus Lentivirus within the family of Retroviridae, subfamily Orthoretrovirinae. 
Up until the 1980s no one knew how many people had HIV or how many developed AIDS. Thanks to a HIV blood test (Robert Gallo, University of Maryland), facilitation of the turning point in the AIDS epidemic through the introduction of combination antiretroviral therapies (cART; David Ho, Rockefeller University and 1996 Time Man of the Year), and other seminal discoveries, epidemiologists have been able to record and note a decline in the estimated annual HIV infections. Based on 2016 estimates, approximately 36.7 million people worldwide were living with HIV/AIDS. 


When compared to the general population, it is important to remember that cART reduces, but does not completely eliminate the risk of AIDS-defining and non-AIDS defining conditions, such as different types of cancer:
•    According to the US Centers for Disease Control and Prevention (CDC), the case definition for AIDS is  the following:  “a person with HIV must have an AIDS-defining condition or have a CD4 count less than 200 cells/mm³ (regardless of whether the person has an AIDS-defining condition).” [6]
•    Kaposi sarcoma, aggressive B-cell non-Hodgkin lymphoma, and cervical cancer fall into the category of cancers in someone infected with HIV that confirms a diagnosis of AIDS. 
•    While the case definition focuses on T cells, it is worth noting that long-term HIV+ survivors have a much higher incidence of B-cell lymphomas (non-AIDS-defining cancers).[6]
 
Sources
1.    Petruzziello A et al. "Global epidemiology of hepatitis C virus infection: An up-date of the distribution and circulation of hepatitis C virus genotypes." World Journal of Gastroenterology, 22; 2016 (7824-7840).
2.    US Centers for Disease Control and Prevention. Hepatitis C and Baby Boomers (1945-1965) [https://www.cdc.gov/knowmorehepatitis/learnmore.htm]
3.    Whiteman H: Hepatitis C linked to increased risk of liver cancer, other cancers. In: MedicalNews Today. Brighton, United Kingdom: Healthline Media 2015.
4.    The Antiretroviral Therapy Cohort C. "Causes of Death in HIV-1–Infected Patients Treated with Antiretroviral Therapy, 1996–2006: Collaborative Analysis of 13 HIV Cohort Studies." Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 50; 2010 (1387-1396).
5.    Wieland SF et al. "Stealth and cunning: hepatitis B and hepatitis C viruses." J Virol, 79; 2005 (9369-9380).
6.    Wang X et al. "Human Immunodeficiency Virus Tat Protein Aids V Region Somatic Hypermutation in Human B Cells." mBio, 9; 2018 (e02315-02317).

 

 

 

 

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