Seble G. Kassaye, M.D., M.S. Assistant Professor of Medicine Division of Infectious Diseases and Travel Medicine Georgetown University

Seble G. Kassaye, M.D., M.S. Assistant Professor of Medicine Division of Infectious Diseases and Travel Medicine Georgetown University November 5, 2016

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HIV epidemiology Global U.S. Washington, D.C. Goals for treatment and prevention UNAIDS U.S. National AIDS Strategy Why do we still have an epidemic HIV care continuum Treatment outcomes Effect on transmission

Pneumocystis Pneumonia --- Los Angeles In the period October 1980-May 1981, 5 young men, all active homosexuals, were treated for biopsy-confirmed Pneumocystis carinii pneumonia at 3 different hospitals in Los Angeles, California. Two of the patients died Case reports of these patients follow. MMWR Weekly June 18, 1982 / 31(23);305-7. A Cluster of Kaposi's Sarcoma and Pneumocystis carinii Pneumonia among Homosexual Male Residents of Los Angeles and range Counties, California MMWR Weekly June 11, 1982 / 31(22);294,300-1. Epidemiologic Notes and Reports Update on Kaposi's Sarcoma and Opportunistic Infections in Previously Healthy Persons -- United States June 1, 1981 - May 28, 1982: 355 cases of Kaposi's sarcoma, Pneumocystis carinii pneumonia (PCP), and other opportunistic infections Profile of affected individuals: previously healthy persons Ages 15 and 60 years of age 281 (79%) were homosexual (or bisexual) men 41 (12%) were heterosexual men 20 (6%) were men of unknown sexual orientation 13 (4%) were heterosexual women

CDC has received reports of four infants (under 2 years of age) with unexplained cellular immunodeficiency and opportunistic infections. Clinical features (12 infants): failure to thrive (83%) oral candidiasis (50%) hepatosplenomegaly (92%) generalized lymphadenopathy (92%) chronic pneumonitis without a demonstrable infection (83%)

Adults and children estimated to be living with HIV 2015 North America and Western and central Europe 2.4 million [2.2 million 2.7 million] Eastern Europe & central Asia 1.5 million [1.4 million 1.7 million] Latin America and the Caribbean 2.0 million [1.7 million 2.3 million] Middle East & North Africa 230 000 [160 000 330 000] Western and central Africa 6.5 million [5.3 million 7.8 million] Eastern and southern Africa 19.0 million [17.7 million 20.5 million] Asia and Pacific 5.1 million [4.4 million 5.9 million] Total: 36.7 million [34.0 million 39.8 million]

Children (<15 years) estimated to be living with HIV 2015 North America and Western and central Europe Eastern Europe & central Asia Latin America and the Caribbean 32 000 Middle East & North Africa 11 000 [8600 14 000] Western and central Africa 500 000 [400 000 630 000] [27 000 38 000] Eastern and southern Africa 1.0 million [930 000 1.2 million] Asia and Pacific 190 000 [140 000 170 000] Total: 1.8 million [1.5 million 2.0 million]

An estimated 1.9 million individuals have been infected with HIV in the United States Approximately 698,219 deaths attributed to HIV since the start of the epidemic ~ 44,073 new infections in 2014 19% decline from 2005-2014 Heterogeneity among subgroups and by region http://www.cdc.gov/hiv/pdf/library/reports/surveillance/cdc-hiv-surveillance-reportus.pdf http://www.cdc.gov/hiv/statistics/overview/ataglance.html

Overarching goals Decrease new HIV infections Focus on key populations and geographic areas Improve health outcomes among HIV-infected individuals Focus on HIV care continuum; health care coverage; models of care for holistic approach Address HIV-related disparities and health inequities Address structural constraints, stigma, & discrimination Coordinated national response to the HIV epidemic

People (%) UNAIDS target Target 1: 90% of HIV+ individuals diagnosed Target 2: 90% of diagnosed individuals on ART Target 3: 90% of people with suppressed HIV RNA Highlights of IAS 2015 clinicaloptions.com/hiv UNAIDS: 90-90-90 Global Estimated Gaps 100 80 60 40 20 0 36.9 million HIV Positive People 53% Breakpoint 1: 13.4 million undiagnosed Breakpoint 2: 14.9 million not treated 19.8 million 41% 32% Breakpoint 3: 15.3 million not virally suppressed 15.0 million 11.6 million Diagnosed On ART Viral Suppression* Levi J, et al. IAS 2015. Abstract MOAD0102. Reproduced with permission. *HIV-1 RNA < 1000 copies/ml.

Treatment as prevention HPTN 052: Antiretroviral treatment of discordant couples led to a 96% decrease in HIV transmission Cohen et al. N Engl J Med. 2011 Aug 11; 365(6):493-505. Epub 2011 Jul 18.

Provision of preexposure prophylaxis has been shown to decrease HIV transmission Okwundu CI et al. Cochrane Database Syst Rev 2012;7:CD007189 AVAC March 2015. PrEP Resources. www.avac.org/prep

New HIV infections among children have declined by 50% since 2010. 2015-150 000 [110 000 190 000] children became newly infected with HIV in 2015 2010-290 000 [250 000 350 000] FACT SHEET 2016, GLOBAL STATISTICS 2015. http://www.unaids.org/en/resources/fact-sheet

Health Disparities: Not all get to less than 2% transmission Rate of Perinatally Acquired HIV Infection, According to Year of Birth and Maternal Race or Ethnic Group, 2008 2012.

New HIV infections have fallen by 6% since 2010. 2010-2.2 million [2 million 2.5 million] 2015-2.1 million [1.8 million 2.4 million] FACT SHEET 2016, GLOBAL STATISTICS 2015. http://www.unaids.org/en/resources/fact-sheet

As of December 2015 17 million people accessing antiretroviral therapy 15.8 million in June 2015 46% [43 50%] of all adults living with HIV 7.5 million in 2010 FACT SHEET 2016, GLOBAL STATISTICS 2015. http://www.unaids.org/en/resources/fact-sheet

CDC Fact Sheet: Trends in U.S. HIV Diagnoses, 2005-2014; http://www.cdc.gov/nchhstp/newsroom/docs/factsheets/hiv-data trends-fact-sheet-508.pdf http://www.cdc.gov/hiv/statistics/overview/ataglance.html

Note. Data include persons with a diagnosis of HIV infection regardless of stage of disease at diagnosis. All displayed data have been statistically adjusted to account for reporting delays and missing transmission category, but not for incomplete reporting. a Heterosexual contact with a person known to have, or to be at high risk for, HIV infection. b Includes hemophilia, blood transfusion, perinatal exposure, and risk factor not reported or not identified.

DC has the Highest Lifetime Risk of HIV Acquisition in the US http://www.cdc.gov/nchhstp/newsroom/images/2016/croi_lifetime_risk_state.j pg

HIV Acquisition risk by transmission category/race: --Highest among MSM --Particularly high among African American MSM

HIV Care Continuum

Undiagnosed: N=156,300 (~13%) Age 13-24 Undiagnosed: N=25,300 (44% of infected in age group) HIV/AIDS Care Continuum: U.S. Department of Health and Human Services. 2013

HIV/AIDS Care Continuum: U.S. Department of Health and Human Services. 2013

* HIV prevalence is increasing Currently ~2.5% 27% of HIV-positive individuals are women 2014 new diagnoses: 396 New diagnoses decreasing 497 new diagnoses in 2013; 396 cases in 2014 In part due to better surveillance/ active testing Annual Epidemiology and Surveillance report 2015

Late presentation rate is still substantial Annual Epidemiology and Surveillance report 2012

MSM closely followed by heterosexual are reported as risk factor for acquiring HIV Annual Epidemiology and Surveillance report 2015

Incidence estimate: 123.6/100,000 Highest % new infections Men 65.9% African American 73.2% Age 13-29 47.9% MSM 49.9%

http://aidsvu.org/state/district-of-columbia/

Inclusion criteria HIV-positive DC WIHS women Contributed at least four semi-annual visits Total sample size 329 women Contributed 6633 visits between 1994-2012 (visits 1-37) Logistic trajectory analysis was used to identify groups of viral load suppression Cumulative viral load suppression-years was used to verify groups found above Multinomial regression analysis with generalized estimating equations for repeated measures was used to explore group characteristics

Ocampo, Plankey, Zou, Collmann, Wang, Young, Liu, Ripple, and Kassaye. BMC Public Health (2015) 15:1277 *Joanne Michelle F. Ocampo and Seble Kassaye share first authorship.

Cumulative years of viral suppression 14 12 10 8 6 4 2 Sustained viremia (N visits =2842) Intermittent viremia (N visits =2575) Non-viremia (N visits =1683) VISIT YEARS Visit 1 = 1994 Visit 36 = 2012 0 0 5 10 15 20 25 30 35 40 Visits A dose-response effect was seen in the cumulative years of viremia by viremic state, with the highest cumulative years of viremia amongst sustained viremic and lowest among nonviremic groups Ocampo, Plankey, Zou, Collmann, Wang, Young, Liu, Ripple, and Kassaye. BMC Public Health (2015) 15:1277 *Joanne Michelle F. Ocampo and Seble Kassaye share first authorship.

Ocampo, Plankey, Zou, Collmann, Wang, Young, Liu, Ripple, and Kassaye. BMC Public Health (2015) 15:1277 *Joanne Michelle F. Ocampo and Seble Kassaye share first authorship. Sustained suppression 4.9% Intermittent viremia 6.9% Sustained viremia 31.1%

Variables analyzed with detection limit at 80 copies/ml Above high school education Adherence ( 95%) Age CD4N/100 Depression (CESD2 16) Drug abuse Ethnicity (African-American) Ethnicity (Hispanic-American) Ethnicity (other) Housing No therapy Therapy (ART)^ Univariate analysis Multivariate analysis OR (CI) P-value OR (CI) P-value 0.52 0.58 0.0079 (0.32-0.84) (0.36-0.95) 0.0294 0.33 0.67 <.0001 (0.26-0.41) (0.51-0.88) 0.0037 1.01 1.03 0.5108 (0.99-1.03) (1.01-1.06) 0.0058 0.85 0.87 <.0001 (0.80-0.91) (0.82-0.93) <0.0001 1.86 1.38 <.0001 (1.38-2.49) (1.03-1.84) 0.0299 1.90 1.34 0.0015 (1.28-2.82) (0.89-2.03) 0.1622 2.58 2.15 0.0019 (1.42-4.69) (1.15-4.01) 0.0169 0.57 0.59 0.2355 (0.22-1.45) (0.22-1.56) 0.284 1.95 1.69 0.3388 (0.50-7.60) (0.47-6.11) 0.4234 0.71 0.87 0.0518 (0.50-1.00) (0.61-1.24) 0.4445 4.02 3.53 <.0001 (2.77-5.84) (2.28-5.47) <.0001 1.95 1.38 <.0001 (1.45-2.63) (0.97-1.96) 0.0739 Factors associated with sustained viremic HIV treatment careers: positively associated: African American ethnicity, older age, depression, and no therapy, negatively associated: higher CD4+ T-cell count, higher education, and higher adherence

HIV-positive women s comments on taking HIV treatment, including for treatment as prevention: Takin a bunch of medication is no fun, you know. Visiting doctors, copays. It s at-it s annoying...it literally changes your life and who wants to go through that if you don t have to if it's not broke, why fix it?"

Percentage (%) 40 35 Percentage (%) 35 30 25 20 15 10 5 0 28.9 24.7 19.7 0 1 2 3 4 Time period 1994-1996 1997-2006 2007-2013 30 25 20 15 10 5 0 0 28.9 1.7 7.9 18 14.6 4.8 10.311.1 1994-1996 1997-2006 2007-2013 PI NRTI NNRTI Time period Treatment naïve N=561 Overall TDR: 126 (22.5%) Kassaye S, Grossman, Z, Balamane M, Johnston-White B, Liu C, Kumar P, Young M, Sneller M, Sereti I, Dewar R, Rehm C, Meyer III W, Shafer R, Katzenstein D, and Maldarelli F. Transmitted HIV Drug Resistance High and Longstanding in Metropolitan Washington, D.C. Clinical Infectious Diseases; June 15, 2016. doi: 10.1093/cid/ciw382

Gender and HIV acquisition risk factor associated with falling into a cluster, but not by race/ethnicity 14% fall within a transmission cluster 32 dyads, 5 triads Men were more likely to fall into a cluster than women: 20% vs 6% (p<0.0001) MSM more likely to fall in a cluster than those with heterosexual risk: 22% vs 14% (p=0.046) Transmitted drug resistance was seen among 6 individuals in cluster Kassaye S, Grossman, Z, Balamane M, Johnston-White B, Liu C, Kumar P, Young M, Sneller M, Sereti I, Dewar R, Rehm C, Meyer III W, Shafer R, Katzenstein D, and Maldarelli F. Transmitted HIV Drug Resistance High and Longstanding in Metropolitan Washington, D.C. Clinical Infectious Diseases; June 15, 2016. doi: 10.1093/cid/ciw382

MSM, heterosexual (male and female) HIV-positive partner Recent STI High number of sex partners Inconsistent/no condom use Sex work Heterosexual women and men In high prevalence area or network IDU HIV-positive injecting partner Shared equipment/needles

HIV-negative women were enthusiastic about PrEP for HIV prevention We asked the women why do they want to use PrEP... To save your life was the unison response. HIV-positive women were concerned about side effects and need for frequent clinic visits, laboratory testing/ monitoring, and were concerned that barrier would not be used

http://www.slate.com/blogs/xx_factor/2016/06/17/the_first_citywide_progra m_to_get_black_women_on_prep_is_coming_to_washington.html; JUNE 17 2016 12:48 PM

http://www.cdc.gov/nchhstp/newsroom/images/2016/croi_fo ur_scenarios_graph.jpg

Outbreak of HIV Infection in Southeastern Indiana. Scott County, Indiana: 181 cases of HIV diagnoses October 1 2014 Nov 1 2015 87.8% reported use of ER oxymorphone 92.3% were co-infected with HCV Maximum-Likelihood Phylogenetic Tree of HIV-1 Polymerase Sequences 98.7% highly related