MODULE 1 AAHIVM CORE CURRICULUM 2016 VERSION 1.1

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1 AAHIVM Core Curriculum Epidemiology and the Spread of HIV Presented by: Jeffrey T. Kirchner, DO, FAAFP, AAHIVS Medical Director, LGHP-Penn Medicine, Comprehensive Care for HIV, Lancaster General Hospital Adapted from the 2016 Fundamentals of HIV Medicine authored by: Philip Bolduc, MD, AAHIVS University of Massachusetts Navid Roder, MD, AAHIVS University of Massachusetts Emily Colgate, MD University of Massachusetts HIV Fellow 2 Module goals Provide an overview of the global AIDS pandemic and the US epidemic Demonstrate and apply knowledge about the evolving epidemiology of human immunodeficiency virus (HIV) to both individual and population-wide aspects of clinical practice Educate clinicians and patients about factors driving HIV transmission so they will understand who is at greatest risk and understand the need to reduce new infections among high-risk groups Epidemiology and the Spread of HIV Overview of the World-Wide Pandemic 1

2 The number of persons receiving ART has increased between ,000 (2000) million (2000) 2.7 million (2005) 2.0 million (2005) 1.6 million (2000) 2.2 million (2005) 2.0 million (2014) 1.2 million (2014) 15.8 million (mid-2015) Annual number of people newly infected with HIV Annual number of people dying from HIV-related causes Number of people receiving ART HIV continues to be pandemic Number of newly diagnosed persons is declining in many countries However, number of persons living with HIV increasing due to increasing numbers on ART 1 WHO. Global sector response to HIV Sub-Saharan Africa remains the most heavily affected region in the AIDS epidemic 3 Total People Living with HIV, 2014: 36.9 million ( million) 5 Western, Central Europe and North America 2.4 million ( million) Eastern Europe, Central Asia 1.5 million ( million) Caribbean 280,000 (2, ,000) Middle East and North Africa 240,000 (150, ,000) Asia and Pacific 5 million ( million) Latin America 1.7 million ( million) Sub-Saharan Africa 25.8 million ( million) 3 UNAIDS. UNAIDS Fact Sheet New infections and AIDS-related deaths decline dramatically in South Africa 2 6 Global Epidemic PLHIV: 36.9 million New infections: 2 million Deaths due to AIDS: 1.2 million Sub-Saharan Africa PLHIV: 24.7 million 46% decrease in new infections from % fewer AIDS-related deaths 2 UNAIDS. AIDS by the Numbers

3 Trends in HIV infections are promising in some regions, but not in others 2 New Infections in Caribbean 13,000 50%* Asia and Pacific 340,000 31% Latin America 87,000 17% Sub-Saharan Africa 1.4 million 41% *Trend since Trend since Trend since UNAIDS. AIDS by the Numbers Trends in HIV infections are promising in some regions, but not in others 2 New Infections in Western, Central Europe and North America 85,000 Stable Caribbean 13,000 50%* Asia and Pacific 340,000 31% Latin America 87,000 17% Sub-Saharan Africa 1.4 million 41% *Trend since Trend since Trend since UNAIDS. AIDS by the Numbers Trends in HIV infections are promising in some regions, but not in others 2 New Infections in Western, Central Europe and North America 85,000 Stable Caribbean 13,000 50%* Middle East and North Africa 25,000 7% Asia and Pacific 340,000 31% Latin America 87,000 17% Sub-Saharan Africa 1.4 million 41% *Trend since Trend since Trend since UNAIDS. AIDS by the Numbers

4 Trends in HIV infections are promising in some regions, but not in others 2 New Infections in 2014 Western, Central Europe and North America Eastern Europe, 85,000 Stable Central Asia 140,000 30% Caribbean 13,000 50%* Middle East and North Africa 25,000 7% Asia and Pacific 340,000 31% Latin America 87,000 17% Sub-Saharan Africa 1.4 million 41% *Trend since Trend since Trend since UNAIDS. AIDS by the Numbers Several key demographic subgroups have missed out on recent progress against HIV 2 Adolescent girls and young women Men who have sex with men Transgender people People who inject drugs Prisoners Sex workers 11 2 UNAIDS. AIDS by the Numbers Global HIV/AIDS epidemic: Status and obstacles 3 As of June 2015, 15.8 million people on ART However, 22 million do not have access to treatment, including 1.8 million children 50% of PLHIV unaware of infection in 2014 Late initiation of ART remains common due to limited access to care and treatment 12 3 UNAIDS Fact Sheet

5 HIV has two major clinically significant subtypes 2 major types: HIV-1 and HIV-2 4 HIV-2 found almost exclusively in West Africa 13 Distinct genomes with ~60% genetic difference 4 HIV-2 has a longer incubation period, produces lower plasma viral load, and lead to AIDS in fewer patients HIV-1 has 3 major groups: Groups M (most common), O, N 4 Group M has 11 subtypes, A through K ART seems similarly effective in all subtypes 5-8 Few clinical studies on HIV-2 susceptibility to ART 9-14 HIV-2 susceptible to most NRTIs and PIs, but resistant to NNRTIs in vitro HIV-2 also susceptible to newer drugs, including TDF, FTC, and INSTIs 4 Apetrei C, Marx PA.. Lancet. 2004;364:: Spira S, et al. J Antimicrob Chemother. 2003;51: Gomes P, et al. CROI Abstract Wainberg MA. AIDS. 2004;18(suppl3):S63 S68. 8 Hackett Jr J, et al. IAC Abstract Witvrouw M, et al. Antivir Ther. 2004;9: Colson P, et al. J Med Virol. 2005;75: Damond F, et al. J Clin Microbiol. 2005;43: Rodes B, et al. J Clin Microbiol. 2000: Andreatta K, et al. J Acquir Immune Defic Syndr. 2013;62: Peterson K, et al. Antivir Ther. 2012; 17: Epidemiology and the Spread of HIV Overview of the US Epidemic US epidemic is relatively stable in all adult subgroups except MSM 15,17 15 Diagnoses, % Diagnoses of HIV Infection Among Adults and Adolescents by Transmission Category, United States and 6 Dependent Areas Male-to-male sexual contact Heterosexual contact Injection drug use (IDU) Male-to-male Sexual contact and IDU Other Overview of US Adult Epidemic (2013) 1,218,400 adults and adolescents (>13 years of age) 12.8% unaware of diagnosis Prevalence:18/0,000 New infections by age in significant subgroups: < 35 years: > 50% < 25 years: 22% > 55 years: 9% Year 5

6 New infections in US primarily in males and blacks 15,17 16 Diagnoses Rate (per 0,000 population) Rates of Diagnoses of HIV Infection Among Adults and Adolescents, by Sex and Race/Ethnicity, 2014 United States Males Total rate = American Indian Asian Black/African American Hispanic/Latino Native Hawaiian/other Pacific Islander White Multiple Races Sex Females Total rate = New Infections in 2014 Total: 44,609 81% male, 19% female 94% of male and 30% of female new infections found in blacks New infections outweighing deaths from HIV in US Deaths, n 19,421 16,281 Deaths per 0,000 population Persons with diagnosed HIV, n 801, ,811 Persons with diagnosed HIV per 0,000 population New infections occurring in areas with highest disease burden 15,17 Rates of Diagnoses of HIV Infection Among Adults and Adolescents, 2014 US and 6 Dependent Areas VT 3.5 NH 3.6 MA 12.8 RI 11.2 CT.0 NJ 20.4 DE 16.8 MD 22.7 DC Areas of highest disease burden also areas with greatest new infections: South, New York, New Jersey, Washington, DC Lower incidence compared with prevalence in California Nevada Illinois Massachusetts Mid-Atlantic States American Samoa 0.0 Guam 0.0 Northern Mariana Islands 0.0 Puerto Rico 22.7 Republic of Palau 0.0 U.S. Virgin Islands

7 Rise in HIV prevalence is not limited to early-stage disease 15,18 Rates of Adults and Adolescents Living with Diagnosed HIV Infection Ever Classified as Stage 3 (AIDS), Year-end 2013 US and 6 Dependent Areas VT 47.9 NH 55.0 MA RI CT NJ DE MD DC 1, In 2013, 508,539 persons living with AIDS Increased from 454,443 in 2008 In 2014, 48% of newly diagnosed cases already Stage 3 (AIDS) New AIDS diagnoses concentrated in the South and in Washington, DC 18 CDC NHHSTP Atlas, American Samoa 2.4 Guam 25.6 Northern Mariana Islands 5.3 Puerto Rico Republic of Palau 5.7 U.S. Virgin Islands In 2012, only 30% of those with HIV were on ART with virologic suppression Persons Living with Diagnosed or Undiagnosed HIV Infection HIV Care Continuum Outcomes, 2009, 20, 2011, and 2012, US and Puerto Rico Diagnosed Received Medical Care Prescribed ART Viral Suppression National HIV/AIDS Strategy for the United States. Overview Epidemiology and the Spread of HIV Spread of HIV Among Women, Children and Adolescents 7

8 Women account for > 50% of PLHIV worldwide and 24% in US 3.7 Rates of Diagnoses of HIV Infection Among Adult and Adolescent Females, 2013 United States and 6 Dependent Areas VT 0.4 NH 1.1 MA 8.3 RI 4.0 CT 4.4 NJ 14.2 DE 8.2 MD 23.5 DC 53.2 Worldwide, women account for 50% of PLHIV 20 In US, women 24% of PLHIV in ,479 new diagnoses in ~6500 stage 3 (AIDS) 15 HIV incidence in women greatest in South, Washington, DC, Illinois, Nevada, Northeast CDC. HIV in the United States CDC. HIV/AIDS Resource Library Slide Sets 20. AmfAR Statistics: Women and HIV/AIDS American Samoa 0.0 Guam 0.0 Northern Mariana Islands 0.0 Puerto Rico 11.4 Republic of Palau 0.0 U.S. Virgin Islands 34.9 Black women account for majority of new HIV diagnoses in US females 15,17 Rates of Diagnoses of HIV Infection Among Female Adults and Adolescent Women by Race/Ethnicity, 2014 United States Diagnoses Rate (per 0,000 population) American Indian/Alaskan Native Asian Black/African American Hispanic/Latino Native Hawaiian/other Pacific Islander White Multiple Races Black women account for 61% of total diagnoses among women Seropositivity rate of black women 19 x higher than white females, 5x higher than Latina females 0 Females, Total rate = 6.1 Infections in females occur primarily through heterosexual contact 15,17 24 Stage 3 (AIDS) Classification Among Adult and Adolescent Females, by Transmission Category and Age at Diagnosis 2013 US and 6 Dependent Areas Transmission category, % N=147 Age at Diagnosis (years) N= N= N= N=2915 Injection drug user Heterosexual contact Other Factors that Increase Woman s Risk of Acquiring HIV Lack of knowledge of HIV Ignorance of partner s risk of infection Physical abuse in relationship Drug use Exchanging sex for drugs or money Total

9 PMTCT decreased dramatically with widespread use of ART 15,17 25 Diagnoses, No. Stage 3 (AIDS) Classifications Among Perinatally Infected Persons, United States and 6 Dependent Areas Year of Diagnosis 2005 Aged <13 years Aged 13 years 20 Rate of perinatal HIV Infection in 2008: 6.8/0,000 live births CDC goal for 2015: reduce by 25% to 5.1/0,000 Of those > 13 years, only 36% were HIV+ in first year of life 66% of HIV+ children are black US Pediatric Year Infections High percentage of black youths among HIV-positive adolescents and young adults 15,17 26 Stage 3 (AIDS) Classification Among Persons Aged 13 Years and Older with HIV Infection, by Race/Ethnicity and Age Group, 2013 US and 6 Dependent Areas 13 to 19 Years 20 to 24 Years 25 Years N=470 N=2266 N=24,391 <1% 16% 2% <1% 1% 3% <1% 1% 3% <1% 2% 5% <1% 18% American Indian/Alaskan Native Asian Black/African American Hispanic/Latino 12% 27% 76% 65% 47% <1% 22% Native Hawaiian/other Pacific Islander White Multiple races 59% of adolescents and young adults diagnosed in 2013 were black MSM transmission risk increased between 2009 and 2013 (72% to 80%) Heterosexual risk decreased (20% to 14%) Females comprised 19% of HIV+ adolescents and 11% of HIV+ young adults Females infected primarily though heterosexual contact Males infected primarily by same-sex contact Epidemiology and the Spread of HIV Spread of HIV Among Men and Women in Communities of Color 9

10 In US, black racial group affected most disproportionately by HIV 15,17 28 Diagnoses, % Diagnoses of HIV Infection Among Adults and Adolescents, by Race/Ethnicity, US and 6 Dependent Areas Black/African American White Hispanic/Latino Native Hawaiian/ other Pacific Islander Asian Multiple races 44% American Indian/ Alaska Native PLHIV 44% are black; only 13% of the US population is comprised of this race Highest risk demographic in US: young black MSM who lives in the South MSM infections: 38% black, 27% Hispanic Year of Diagnosis 17 CDC. HIV/AIDS Resource Library Slide Sets. 21 Valleroy Fitzpatrick Millett AIDS diagnoses increasing for US blacks and Hispanics; decreasing for whites, others 15,17 29 Percentages of Stage 3 (AIDS) Classifications Among Adults and Adolescents with Diagnosed HIV Infection, by Race/Ethnicity and Year of Diagnosis, US and 6 Dependent Areas 70 Diagnoses, % White Hispanic/Latino Black/African American 0 Multiple races Asian American Indian/Alaska Native Native Hawaiian/other Pacific Islander Year of Diagnosis Black women account for 61% of new diagnoses among women in US 15,17 30 Diagnoses of HIV Infection Among Adults and Adolescents, by Sex and Race/Ethnicity, 2014 US and 6 Dependent Areas 2% <1% 2% 2% 1% 2% American Indian/Alaskan Native Asian Black/African American <1% 18% Hispanic/Latino Native Hawaiian/other Pacific Islander White Multiple races <1% 29% Males N=36,138 40% 18% Females N= % 26%

11 Death rates among HIV+ black persons 8 times higher than HIV+ white persons 15,17 31 Deaths of Persons with Diagnosed HIV Infection by Race/Ethnicity, 2013 US Race/ethnicity Number Rate American Indian/Alaskan Native Asian Black/African American Hispanic/Latino Native Hawaiian/other Pacific Islander White Multiple races Total 16, Epidemiology and the Spread of HIV Spread of HIV Among Immigrant Populations 33 Immigrants Refugees no longer routinely tested for HIV upon entry in US CDC universal opt-out screening recommendations include refugees 26 Screening for HIV-2 recommended for those persons from West Africa Variable rates of HIV diagnoses in different immigrant populations 16 For Hispanics, the rate is 460/0,000 (higher than white US-born persons) For foreign-born New Yorkers, rate of diagnosis lower than US-born counterparts Immigrants significantly younger, more likely to present with indicators of more advanced HIV disease, had lower CD4+ counts, and were more likely to be hospitalized at the time of HIV diagnosis than US-born patients CDC. HIV Surveillance Report CDC (Branson B, et al). MMWR. September 22, 2006/55(RR14); Levy V, et al. J Immig Minor Health. 2007; 9(1):

12 Epidemiology and the Spread of HIV The Evolving Role of the Gay Community in the Spread of HIV MSM still constitute largest percentage of persons diagnosed with HIV/AIDS in US 15 Individuals who identify as gay or bisexual are only population group in US in which infections have continued to rise since early 1990s In 2013, 80.6% of all diagnosed infections in adult and adolescent males attributed to male-to-male sexual contact Estimated number of diagnoses increased 12% from 2009 to 2013 Infections among those years of age increased 25% Infections among those 55 years of age increased 29% 35 Transgender persons comprise high-risk group for acquiring HIV infection 15 In 20, highest percentage of newly identified HIV+ test results was among transgender people 36 In New York City between diagnoses among transgender people 99% transgender women; 90% of those black or Latino 52% of these were years of age 51% had documented substance abuse, commercial sex work, homelessness, incarceration, and/or sexual abuse 12

13 37 Summary Worldwide, the number of new diagnoses of HIV is declining; however, the number of PLHIV continues to increase due to increasing access to ART In the US, the CDC documents that the HIV/AIDS epidemic is stable but only 30% of HIV-infected persons are virologically suppressed on ART HIV is present in all 50 states, in both sexes, and in all age groups The burden of disease in the US is borne primarily by blacks; the demographic group with risk is black MSM Men who have sex with men are the only population group in which new HIV infections continue to rise The success story in both the US and worldwide is the decrease in PMTCT by effective testing and treatment strategies for pregnant women Important implications of the current HIV epidemic are that more clinicians will be needed to care for the burgeoning HIV population and more must be done to prevent HIV transmission 38 References 1. World Health Organization. Global health sector response to HIV, Available at Accessed March 26, UNAIDS. AIDS by the Numbers World AIDS Day Report. Available at Accessed March 26, UNAIDS. UNAIDS Fact Sheet Available at Accessed March 26, Apetrei C, Marx PA. Simian retroviral infections in human beings. Lancet. 2004;364: Spira S, Wainberg MA, Loemba H, et al. Impact of clade diversity on HIV-1 virulence, antiretroviral drug sensitivity and drug resistance. J Antimicrob Chemother. 2003; 51: Gomes P, Diogo I, Gonca Ives MF, et al. Different pathways to nelfinavir genotypic resistance in HIV-1 subtypes B and C. In: Program and abstracts of the 9th Conference on Retroviruses and Opportunistic Infections; February 24-28, 2002; Seattle, WA. Abstract Wainberg MA. HIV-1 subtype distribution and the problem of drug resistance. AIDS. 2004;18(suppl3):S63 S Hackett Jr J, Holzmayer V, Swanson P, et al. Analysis of HIV-1 genetic diversity in London and its impact on the performance of viral load assays. In: Program and abstracts of the XV International AIDS Conference: July 11-16, 2004; Bangkok, Thailand. Abstract Witvrouw M, Pannecouque C, Switzer VM, et al. Susceptibility of HIV-2, SIV and SHIV to various anti-hiv-1 compounds: implications for treatment and postexposure prophylaxis. Antivir Ther. 2004;9: Colson P, Henry M, Tivoli N, et al. Polymorphism and drug-selected mutations in the reverse transcriptase gene of HIV-2 from patients living in southeastern France. J Med Virol. 2005;75: References (cont.) 11. Damond F, Brun-Vezinet F, Matheron S, et al. Polymorphism of the human immunodeficiency virus type 2 (HIV-2 protease gene and selection of drug resistance mutations in HIV-2-infected patients treated with protease inhibitors. J Clin Microbiol. 2005;43: Rodes B, Holguin A, Soriano V, et al. Emergence of drug resistance mutations in human immunodeficiency virus type 2- infected subjects undergoing antiretroviral therapy. J Clin Microbiol. 2000: Andreatta K, Miller, MD, White KL. HIV-2 antiviral potency and selection of drug resistance mutations by the integrase strand transfer inhibitor elvitegravir and NRTIs emtricitabine and tenofovir in vitro. J Acquir Immune Defic Syndr. 2013;62: Peterson K, Ruelle J, Vekemans M, et al. The role of raltegravir in the treatment of HIV-2 infections: evidence from a case series. Antivir Ther. 2012; 17: "US Centers for Disease Control and Prevention. HIV in the United States Available at: Accessed March 26, " 16. "CDC. HIV Surveillance Report, 2014; vol. 26. Published November Available at: Accessed March " 17. US Centers for Disease Control and Prevention. HIV/AIDS Resource Library Slide sets. Available at Accessed March 26, US Centers for Disease Control and Prevention. NHHSTP Atlas, Available at Accessed March 26, National HIV/AIDS Strategy for the United States: Update to Accessed March 26, AmfAR (American Foundation for AIDS Research) Statistics: Women and HIV/AIDS. Accessed March 26,

14 40 References (cont.) 21. Valleroy LA, MacKellar D, Behel S, Secura G. The bridge for HIV transmission to women from 15- to 29-year-old men who have sex with men in 7 US cities. In: Program and abstracts of the XV International AIDS Conference; July 11-16, 2004; Bangkok, Thailand. Abstract Fitzpatrick LK, Grant L, Eure C, et al. Investigation of HIV transmission among young black men who have sex with men (MSM) in North Carolina: Implications for prevention. In: Program and abstracts of the XV International AIDS Conference; July 11-16, 2004; Bangkok, Thailand. Abstract C Millett G. Men on the down low : more questions than answers. In: Program and abstracts of the 11th Conference on Retroviruses and Opportunistic Infections; February 8-11, 2004; San Francisco, California. Abstract Sanchez MA, Lemp GF, Magis-Rodriquez C, et al. The epidemiology of HIV among Mexican migrants and recent immigrants in California and Mexico. J Acquir Immune Defic Syndr Suppl 4:S204-S Magis-Rodriguez C, Lemp G, Hernandez MT, et al. Going North: Mexican migrants and their vulnerability to HIV. J Acquir Immune Defic Syndr. 2009;51 Suppl 1: S21-S "CDC (Branson B, et al). revised recommendations for HIV testing of adults, adolescents, and pregnant women in healthcare settings. MMWR. September 22, 2006 / 55(RR14);1-17." 27. Centers for Disease Control and Prevention. Revised Surveillance Case Definition for HIV- United States, Recommendations and Reports. 2014; 63(RR03); Organista KC, Carillo H, Avala G. HIV prevention with Mexican migrants: review, critique, and recommendations. J Acquir Immune Defic Syndr. 2004; 37 Suppl4:S227-S Levy V, Prentiss D, Balmas G et al. Factors in the delayed HIV presentation of immigrants in Northern California: implications for voluntary counseling and testing programs. J Immig Minor Health. 2007; 9: AAHIVM Core Curriculum Epidemiology and the Spread of HIV Presented by: Jeffrey T. Kirchner, DO, FAAFP, AAHIVS Medical Director, LGHP-Penn Medicine, Comprehensive Care for HIV, Lancaster General Hospital Adapted from the 2016 Fundamentals of HIV Medicine authored by: Philip Bolduc, MD, AAHIVS University of Massachusetts Navid Roder, MD, AAHIVS University of Massachusetts Emily Colgate, MD University of Massachusetts HIV Fellow 14