1. Core Competency 1: Epidemiologic Background of HIV/HCV Co-infection in the United States
Lesson 1: Epidemiology
July 2017

2. Authors and Funders
This presentation was prepared by Francine Cournos, MD, (Northeast/Caribbean AETC) for the AETC National Coordinating Resource Center in July 2017.
This presentation is part of a curriculum developed by the AETC Program for the project: Jurisdictional Approach to Curing Hepatitis C among HIV/HCV Co- infected People of Color (HRSA ), funded by the Secretary's Minority AIDS Initiative through the Health Resources and Services Administration HIV/AIDS Bureau. 

3. Lesson Objectives
Identify and understand epidemiologic trends in HCV in the United States
Review the available data on epidemiologic trends in HIV/HCV co-infection in the United States
Identify how epidemiologic in the United States trends apply to MSM, PWID, and people of varying demographic characteristics such as gender, age, and race/ethnicity
HCV = Hepatitis C Virus
HIV = Human Immunodeficiency Virus
MSM = Men who have Sex with Men
PWID = People Who Inject Drugs

4. Epidemiology of HCV in the United States1
HCV is the most common chronic blood borne infection2
About 3.5 million people are chronically infected with HCV in the United States3
About half are unaware that they are infected4
The majority of HCV infections occur among individuals born between 1945 and 19655

5. Estimated HCV Prevalence by Decade of Birth
1.6
1.4
1.2
1.0
0.8
0.6
0.4
0.2
1990+
1980s
1970s
1960s
1950s
1940s
1930s
1920s
<1920
Number with chronic HCV (millions)
Baby boomers (born ) account for >75% of HCV infections in the United States6-7 HCV is unusual in that it disproportionately affects baby boomers -- 82% of people infected with HCV were born from 1945 through 1965 (Figure). A majority of these people acquired HCV in the 1960s through 1980s, so they have lived with HCV for 20 to 40 years. The risk of cirrhosis, liver failure and liver cancer increases with longer duration of infection. In fact, HCV-related cirrhosis is projected to increase from 25% to 37% over the next decade, peaking at over 1 million cases by 2020 if there are no changes in screening, diagnosis, and treatment6 .
Pyenson B, Fitch KV, Iwasaki K. Consequences of Hepatitis C Virus (HCV): Costs of a baby boomer Epidemic of Liver Disease. New York, NY: Milliman, Inc; May 2009.
Graham, Adapted from Pyenson, 2009.

6. Estimated Incidence of HCV Infection over Time7
The graphic represents the estimated number of new hepatitis C infections per year in the United States.
HCV incidence peaked in the late 1980s and early 1990s at about 230,000 new infections per year7.
After that, rates dropped, first among recipients of blood, blood products, and organs, and then among PWID.
In 2014, the annual estimated incidence was 30,500.
CDC, 2015

7. Reported Cases of Acute HCV in the United States over Time7
This chart details the incidence of REPORTED acute HCV by year.
Note how the actual REPORTED number of acute HCV cases markedly differs from the ESTIMATED number of cases annually per the CDC.
The definition of acute HCV, along with the natural history of the disease (where many persons are asymptomatic after infection), make the epidemiology of acute HCV difficult to accurately grasp.
CDC, 2015

8. People at Risk of HCV Infection8
Current or former PWID
Recipients of clotting factor concentrates before 1987
Recipients of blood transfusions or donated organs before July 1992
Long-term hemodialysis patients
People with known HCV exposures
PLWH (primarily PWID and MSM)
Infants born to HCV-infected mothers
PWID = People Who Inject Drugs
MSM = Men who have Sex with Men

9. PWID Are Most at Risk of HCV Infection1,8
IDU
Most common means of HCV transmission in the United States
~33% of PWID aged are infected, but these rates are increasing
~70-90% of older PWID are infected
Intranasal drug use is also a risk factor
This slide relies on CDC data. Other sources of data may give different estimates. Our understanding of HCV epidemiology is incomplete.
Haddad, 2015

10. People with HCV Infection and Incarceration8
33% of incarcerated persons in the United States are living with HCV
Treatment in correctional settings would offer significant health benefits to inmates and the communities to which they will return

11. Trends in IDU by Race9
Between 2005 and 2015, the number of new PWID in the progressively increased among Whites and decreased among Blacks
However, HIV/HCV co-infection remains much more prevalent among Blacks than among Whites, so racial disparities remain prominent among co-infected people

12. Heterosexual Transmission of HCV
HIV-uninfected men or women engaging in heterosexual activity with HCV-infected partners:
Cross-sectional studies report HCV prevalence among regular heterosexual partners as being between 2% and 10%. This could in part be a cohort effect or a result of sharing drug paraphernalia.10
Transmission between monogamous heterosexual partners without other risk factors is rare10; a recent study estimated the risk as 1/190,000 sexual contacts11
Risk is increased by having multiple partners, having another STI, or exchanging blood during sex11
When evaluating couples where both people were born between , the cohort effect refers to the fact that they may have each acquired HCV infection independently of one another given the greater frequency of common shared risk factors for that birth cohort. Couples may also be sharing drug injection equipment but not report this practice.

13. Heterosexual Transmission of HCV among PLWH10
PLWH engaging in opposite-sex sexual activity with HCV-infected partners are more likely to acquire HCV infection

14. Sexual Transmission of HCV among MSM1,10,12
Sex with HCV-infected persons
HIV-uninfected MSM
Sexual transmission occurs but is infrequent
HIV-infected MSM
Are at increased risk of sexual transmission of HCV
This appears more likely to occur in the context of risk factors such as stimulant use, unsafe sex practices, and genital ulcerations
HIV-uninfected MSM
Amsterdam study: 0 cases/100 person years
UK study: 1.5 cases/1,000 person years
Studies in Canada, Argentina, Australia: no association with sexual transmission (if no IDU present)
Slide adapted from Haddad, M. New Era of HCV Management: Innovations in Primary Care. Sep 24, Presentation online:
Haddad, 2015

15. HCV Genotype Distribution in the United States
6 known GT
Little difference among them re: transmission and natural history
GT 1 most common
Slide adapted from Haddad, M. New Era of HCV Management: Innovations in Primary Care. Sep 24, Presentation online:
Haddad, 2015

16. HCV Morbidity and Mortality without Treatment13
Without treatment, decompensated cirrhosis and HCC would rise into the 2020s.
Projected number of cases by year of decompensated cirrhosis (purple) and hepatocellular carcinoma (green). The model assumes a first year mortality of 80% to 85%, so in contrast to the decompensated cirrhosis projection, the number of cases of hepatocellular carcinoma the prevalence demonstrated here closely resembles annual incidence of liver cancer.
Without the advantage of effective new treatments, decompensated cirrhosis cases will continue to increase through
Without the advantage of effective new treatments, hepatocellular carcinoma is expected to peak in 2019 at 14,000 cases.
This slide does not reflect the impact of direct-acting antivirals for HCV infection.
Morbidity and mortality due to HCV infection are projected to rise into the 2020s as illness and deaths from decompensated cirrhosis and HCC peak among baby boomers, the generation with the highest infection rates
The delayed effect of morbidity and mortality following initial HCV infection reflects the long time period that usually passes between initial infection and the onset of severe hepatic illness
Widespread treatment of HCV infection would diminish but not totally reverse this projected increase in mortality
Davis, 2010

17. Effective Treatment Will Significantly Reduce Mortality from HCV Infection14
SVR is considered a cure for HCV.
From HCV Guidance:
“Numerous studies have demonstrated that hepatitis C therapy and the achievement of an SVR in this population results in dramatic decreases in hepatic decompensation events, hepatocellular carcinoma, and liver-related mortality. (Morgan, 2013); (van der Meer, 2012); (Backus, 2011); (Dienstag, 2011); (Berenguer, 2009); (Mira, 2013) In the HALT-C study, patients with advanced fibrosis secondary to HCV infection who achieved an SVR, compared with patients with similarly advanced liver fibrosis who did not achieve an SVR, had a decreased need for liver transplantation (hazard ratio [HR], .17, 95% confidence interval [CI], .06–.46), development of liver-related morbidity and mortality (HR, .15, 95% CI, .06–.38) and hepatocellular carcinoma (HR, .19, 95% CI, .04–.80).”
van der Meer AJ et al. JAMA. 2012

18. HCV Deaths Surpassed HIV Deaths in 2006-715
15,106
12,734
FIGURE. Annual age-adjusted mortality rates from hepatitis B and hepatitis C virus infections and HIV infections listed as causes of death in the United States between 1999 and 2007.
In the United States, the annual number of deaths due to HCV infection are increasing, and have risen above that of HIV infection.
Notes
In an analysis of ~22 million death certificates from 1999 to 2007, the mortality rate due to HCV infection increased to 15,106 in During the same timeframe, deaths due to HBV remained relatively constant (1815 deaths in 2007) and HIV-related deaths decreased slightly to 12,734.1
During the study period, annual deaths due to HCV surpassed that of HIV infection.1
While these data indicate the increasing mortality burden of chronic HCV infection, deaths due to HCV are frequently underreported; thus the accurate mortality is likely to be higher than is captured by death certificates.1,2
Because a decedent can have multiple causes of death, a record listing more than 1 type of infection was counted for each type of infection.
Ly KN et al. Ann Intern Med. 2012

19. HIV Epidemiology in the U.S.16
1.2 million people living with HIV infection
Sex between men is the predominant mode of HIV transmission
Consequently, men have always had higher rates of HIV infection than women
Blacks are much more likely to be infected than Whites; Latinos/Hispanics also have higher rates of infection than Whites, but the difference is less dramatic

20. Recent Rates of HIV Infection by Age at Diagnosis17
This slide presents the rates of diagnoses of HIV infection by age group among adults and adolescents in the United States from 2010 through 2014.
Persons aged 25–34 years accounted for the highest rates of diagnoses of HIV infection each year; whereas, persons aged ≥55 years accounted for the lowest rates of diagnoses of HIV infection each year.
From 2010 through 2014, rates of diagnoses of HIV infection remained stable among persons aged 13–24 years and 25–34 years. Decreases were seen in rates among persons aged 35–44 years (-21.0%), 45–54 years (-19.3%), and ≥55 years (-15.7).
Data include persons with a diagnosis of HIV infection regardless of stage of disease at diagnosis.
Note. Data include persons with a diagnosis of HIV infection regardless of stage of disease at diagnosis.
CDC 2017

21. Recent Diagnoses of HIV Infection by Transmission Category17
This slide presents the percentage distribution of adults and adolescents with diagnosed HIV infection from 2010 through 2014, by transmission category, for the United States and 6 dependent areas.
The percentage of adults and adolescents with diagnosed HIV infection attributed to male-to-male sexual contact increased from 60% in 2010 to 66% in The percentages of diagnosed HIV infections attributed to injection drug use, male-to-male sexual contact and injection drug use, and heterosexual contact decreased from 2010 through The “Other” transmission category is not displayed as it comprises less than 1% of cases. The category includes hemophilia, blood transfusion, perinatal exposure, and risk factor not reported or not identified.
Data include persons with a diagnosis of HIV infection regardless of stage of disease at diagnosis. Data have been statistically adjusted to account for missing transmission category.
Heterosexual contact is with a person known to have, or to be at high risk for, HIV infection.
Note. Data include persons with a diagnosis of HIV infection regardless of stage of disease at diagnosis. Data have been statistically adjusted to account for missing transmission category. “Other” transmission category not displayed as it comprises less than 1% of cases.
a Heterosexual contact with a person known to have, or to be at high risk for, HIV infection.
CDC 2017

22. Transmission Categories for Newly Diagnosed HIV among Men, 201517
82% MSM contact
9% heterosexual contact
5% IDU
4% combination of MSM and IDU
CDC data: Of the 32,422 HIV infections diagnosed in 2015 among male adults and adolescents, approximately 82% were attributed to male-to-male sexual contact. An additional 4% of diagnosed infections were attributed to male-to-male sexual contact and injection drug use.
Injection drug use accounted for 5% of diagnosed HIV infection, heterosexual contact accounted for 9%. The “Other” transmission categories accounted for less than 1% of diagnosed HIV infections. The category includes hemophilia or the receipt of blood or blood products, perinatal exposure, and risk factor not reported or not identified.   
Data include persons with a diagnosis of HIV infection regardless of stage of disease at diagnosis. Data for the year 2015 are preliminary and based on 6 months reporting delay.

23. Transmission Categories for Newly Diagnosed HIV Infections among Women, 201517
86% heterosexual contact
13% IDU
In 2015, the majority of diagnoses of HIV infection among female adults and adolescents were attributed to heterosexual contact regardless of age group. However, the percentages attributed to heterosexual contact were higher among females aged 20–24 years (87.9%) than among other age groups. Approximately 14.1% of diagnosed HIV infections among females aged 25–34 years were attributed to injection drug use, compared with 13.3% among both females aged 35–44 years and females aged 45 years and older, 11.3% among females aged 20–24 years, and 8.5% among females aged 13–19 years.
Data include persons with a diagnosis of HIV infection regardless of stage of disease at diagnosis. Data for the year 2015 are preliminary and based on 6 months reporting delay.

24. Newly Diagnosed HIV Infections in 2015 by Race/Ethnicity17
Blacks comprised 12% of the population and 45% of newly diagnosed HIV infections. Hispanics/Latinos comprised 18% of the population and 24% of newly diagnosed HIV infections.

25. HIV Diagnoses and U.S. Population by Race/Ethnicity, 201517
This slide presents the comparison of the racial/ethnic distribution among persons with HIV infection diagnosed in 2015 and the general population.
Note:
Hispanics/Latinos can be of any race.
The lower bar illustrates the distribution of diagnoses of HIV infection in 2015 by race/ethnicity in the United States. The upper bar shows the distribution of the population in the United States by race/ethnicity in 2015.
In 2015, blacks/African Americans made up approximately 12% of the population of the United States, but accounted for 45% of diagnoses of HIV infection. Whites made up 62% of the population of the United States, but accounted for 27% of diagnoses of HIV infection. Hispanics/Latinos made up 18% of the population of the United States, but accounted for 24% of diagnoses of HIV infection.
Data include persons with a diagnosis of HIV infection regardless of stage of disease at diagnosis. Data for the year 2015 are preliminary and based on 6 months reporting delay.    
CDC, 2017

26. Newly Diagnosed HIV Infections in MSM by Region, 201518
The highest rates for Blacks, Whites, and Latinos were found in the South.
This slide presents the number of diagnoses of HIV infection in 2015 among MSM by race/ethnicity and the region of the United States where they were living at the time of diagnosis. Diagnoses of HIV infection among MSM in the 6 U.S. dependent areas are also shown by race/ethnicity.
The South had more diagnoses of HIV infection among MSM — 13,303 diagnoses in 2015 — than any other region. The largest group of MSM with diagnosed HIV infection in the South were blacks/African Americans, followed by whites, Hispanics/Latinos, persons of multiple races, Asians, American Indians/Alaska Natives, and Native Hawaiians/other Pacific Islanders.
In the West, the number of diagnoses of HIV infection among MSM was 5,628. The racial/ethnic group with the largest number of diagnoses were Hispanics/Latinos, followed by whites, blacks/African Americans, Asians, persons of multiple races, American Indians/Alaska Natives, and Native Hawaiians/other Pacific Islanders.
In the Northeast the number of diagnoses of HIV infection among MSM was 3,927. The racial/ethnic group with the largest number of diagnoses were blacks/African Americans, followed by Hispanics/Latinos, whites, persons of multiple races, Asians, American Indians/Alaska Natives, and Native Hawaiians/other Pacific Islanders.
In the Midwest, the number of diagnoses of HIV infection among MSM was 3,516. The racial/ethnic group with the largest number of diagnoses were blacks/African Americans, followed by Hispanics/Latinos, whites, persons of multiple races, Asians, American Indians/Alaska Natives, and Native Hawaiians/other Pacific Islanders.
In the dependent areas, 96% of diagnoses of HIV infection among MSM in 2015 were in Hispanics/Latinos.
Inter-region comparisons of numbers of diagnosed HIV infections should be made cautiously because the four regions and the dependent areas vary by number of jurisdictions and by population size.
Regions of residence are defined as follows: Northeast—Connecticut, Maine, Massachusetts, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, and Vermont; Midwest—Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, Ohio, South Dakota, and Wisconsin; South—Alabama, Arkansas, Delaware, District of Columbia, Florida, Georgia, Kentucky, Louisiana, Maryland, Mississippi, North Carolina, Oklahoma, South Carolina, Tennessee, Texas, Virginia, and West Virginia; West—Alaska, Arizona, California, Colorado, Hawaii, Idaho, Montana, Nevada, New Mexico, Oregon, Utah, Washington, and Wyoming. The 6 U.S. dependent areas include American Samoa, Guam, the Northern Mariana Islands, Puerto Rico, the Republic of Palau, and the U.S. Virgin Islands.
Data include persons with a diagnosis of HIV infection regardless of stage of disease at diagnosis. Data for the year 2015 are preliminary and based on 6 months reporting delay. Data have been statistically adjusted to account for missing transmission category.
Data on men who have sex with men do not include men with HIV infection attributed to male-to-male sexual contact and injection drug use.
 Hispanics/Latinos can be of any race.
CDC, 2017

27. Stage 3 HIV (AIDS) Classifications by Race/Ethnicity and Year19
During the early 1990’s the numbers of HIV infections classified as stage 3 (AIDS) among Whites, Blacks/African Americans and Hispanics/Latinos increased, peaked during 1992–1993, and then decreased since that time. However, decreases were not consistent across races/ethnicities: stage 3 (AIDS) among blacks/African Americans surpassed whites for the first time in 1994 and has remained higher than all races/ethnicities since that time.
This higher rate of advanced HIV infection for Blacks has persisted since that time; it is higher than for Whites or Hispanics/Latinos. Despite this continuing health disparity, rates of advanced HIV disease are diminishing over time across all races and ethnicities, including among Blacks.
a Hispanics/Latinos can be of any race.
CDC, 2017

28. Trends in HIV-related Death Rates by Race/Ethnicity20
Trends in Age-Adjusted* Annual Rates of Death due to HIV Infection by Race/Ethnicity, 1990−201420
The age-adjusted rate of death due to HIV infection has been highest among blacks/African Americans and second highest among Hispanics/Latinos.
In every racial/ethnic group, the rate decreased greatly from 1995 through Among blacks/African Americans, however, the percentage decrease in the rate was smaller (58%) than in the other racial/ethnic groups. The percentage decrease in the other groups ranged from 67% among American Indians/Alaska Natives to 76% among whites.
Hispanics/Latinos can be of any race.
For the calculation of national death rates by race and ethnicity, data for a few states were excluded for the years when death certificates for those states did not collect information on Hispanic/Latino ethnicity. The states for which data were omitted were: Connecticut and Louisiana in 1990, New Hampshire through 1992, and Oklahoma through 1996.
The data for this slide come from death certificate data compiled by the National Center for Health Statistics.
CDC, 2017

29. HIV Infection and Mortality20
HIV-related deaths (2014):
Blacks comprised 53%
Residents of the South comprised 53%
People 45 years of age or older: 72%
HIV infection remains among the 10 leading causes of death among persons years of age
South: Alabama, Arkansas, Delaware, District of Columbia, Florida, Georgia, Kentucky, Louisiana, Maryland, Mississippi, North Carolina, Oklahoma, South Carolina, Tennessee, Texas, Virginia, and West Virginia
Focusing on persons 25 to 44 years old emphasizes the importance of HIV infection among causes of death. Compared with rates among other age groups, the rate of death due to HIV infection is relatively high in this age group, but rates of death due to other causes are relatively low.
HIV infection was the leading cause of death among persons 25 to 44 years old in 1994 and In 1995, HIV infection caused about 32,000 deaths, or 20% of all deaths in this age group. The rank of HIV infection fell to 5th place from 1997 through 2000, to 6th place from 2001 through 2009, then fell to 9th place in 2014 causing about 2,000 deaths, or 2% of all deaths in this age group.
All Groups, 2014 (ages 25-44)
Unintentional injury
Cancer
Heart disease
Suicide
Homicide
HIV infection
The data for this slide come from death certificate data compiled by the National Center for Health Statistics.

30. About 25% of PLWH in the U.S. also Have HCV Infection17,21
HIV
1.2M
HIV 300K HCV
HCV
3.2M
The CDC estimates that there are 2.7–3.9 million people with chronic HCV infection. The likelihood of HIV/HCV co-infection varies across the US by geographic region.

31. Disclaimer and Permissions
Users are cautioned that because of the rapidly changing medical field, information could become out of date quickly.
You may use or present this slide set and other material in its entirely or incorporate into another presentation if you credit the author and/or source of the materials.
The complete HIV/HCV Co-infection: An AETC National Curriculum is available at:

32. Continue to the next lesson
Lesson 1.2: Morbidity and Mortality in Co-infected People Living with HIV