What You May Have Missed at IDWeek 2020

What You May Have Missed at IDWeek 2020 and Elsewhere

Financial Relationships With Commercial Entities Dr. Masur has no relevant financial affiliations to disclose (Updated 11/02/20) Slide 2 of 55

Learning Objectives After attending this presentation, learners will be able to: • List the important findings in the District of Columbia Mayor’s 2020 HIV Report • List newly described issues around health disparities • Implement new approaches to preventing morbidities in an aging HIV population • Describe updates around preexposure prophylaxis (Pr. EP) and opportunistic infections (OIs) Slide 3 of 55

Washington, D. C. Our Nation’s Capital Slide 4 of 55

ARS Question 1 In Washington, D. C. , how many new cases of HIV/AIDS were reported in 2019? A. <10 B. 10 -50 C. 51 -100 D. 101 -500 E. >500 Slide 5 of 55

Newly Diagnosed HIV Disease Cases, Deaths, and Living HIV Cases, by Year, District of Columbia, 1983 -2019 A Journey From 1300 to 270 Incident Cases Per Year! New Cases Deaths Slide 6 of 55 https: //dchealth. dc. gov/service/hiv-reports-and-publications

Mayor’s 90/90/90/50 Ending the HIV Epidemic Plan Goal Update, 2019 HIV Wellness and Prevention Measures 2015 2016 2017 2018 2019 2020 Goal #1: 90% of HIV-positive District residents know their status 86% 87% 88% 90% Goal #2: 90% of District Residents living with HIV are in treatment 73% 76% 77% 80% 90% Goal #3: 90% of District residents living with HIV who are in treatment reach viral suppression 78% 82% 84% 85% 87% 90% Goal #4: 50% reduction in new HIV diagnoses 401 369 371 335 282 196 Slide 7 of 55 https: //dchealth. dc. gov/service/hiv-reports-and-publications

Of Those Newly Diagnosed with HIV Cases in the District Between 2015 -2019 1 in 7 2 in 5 1 in 4 were Black Women Slide 8 of 55 were men who have sex with men of color 1 in 3 were aged 20 -29 Had at least 1 STI diagnosis within 12 mo of HIV diagnosis https: //dchealth. dc. gov/service/hiv-reports-and-publications

Update from ID Week • Health disparities • Aging population • PREP…. . but Monica Gandhi will cover • OIs Slide 9 of 55

The 2020 Kass Lecture Slide 10 of 55

Dr. Adimora’s Reflections from 1980 s • • • Number of sexual partners was an issue in HIV transmission but… High risk behavior was not a factor for many minority patients that Ada was seeing in NYC Poverty and race appeared to be risk factors but…how often and why Slide 11 of 55

Mass Incarceration: A US Phenomenon Slide 12 of 55

Mass Incarceration: A US Phenomenon • Shortage of Black Men ‒ Unstable families ‒ Unstable finances ‒ Concurrency • Lack of continuity of care ‒ Transition in and out of incarceration • Disenfranchisement ‒ Results of Gore vs Bush and others Slide 13 of 55

Federal Govt Plans to End the US HIV Epidemic Slide 14 of 55

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All Policy is Health Policy Slide 16 of 55

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Nationwide, Black People Are Dying of COVID-19 at >Twice the Rate of White People Slide 18 of 55

Health Disparities and COVID • Risk for hospitalization higher for Blacks ▫ Not entirely related to co morbidity • Mortality due to COVID, once patients are hospitalized ▫ No different for Blacks vs Whites • Mortality rates decreased more in Medicaid expansion states than non expansion states Slide 19 of 55

Bottom Line • Racial inequities of HIV and COVID-19 are not inevitable ▫ Result of social, economic and political forces • Changes Can Be Made ▫ Criminal Justice System ▫ Health Care Insurance • These changes will not reverse the effects of centuries of racial injustice but…they will improve the lives of many Americans Slide 20 of 55

The Aging of an Epidemic Complications of HIV and Its Treatment Keri Althoff Ph. D, MPH Johns Hopkins School of Public Health Slide 21 of 55

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Overall and Morbidity Free Survival, Kaiser Permanente, 2000 -2016 Overall Survival Co Morbidity Free Survival Slide 23 of 52

Reducing “Healthspan Disparity” • Interventions to target causes of aging/comorbidities • Delay onset of more than one age related process at same time • Contract period of morbidity before death Slide 24 of 55

Selective Decay of Intact HIV-1 Proviral DNA on Antiretroviral Therapy Rajesh T. Gandhi, and ACTG A 5321 team. Slide 25 of 55

ACTG HIV Reservoir Cohort (AHRC; ACTG A 5321) Median 3. 7 years ART initiation N=50 Slide 26 of 55 Median 7. 1 years Timepoint 1 N=44 Median 1. 8 years Timepoint 2 N=40 Timepoint 3 N=33

Fraction of Intact Proviruses Decreases Over Time on ART 9. 8% Slide 27 of 55 5. 8%

Fraction of Intact Proviruses Decreases Over Time on ART 9. 8% 5. 8% ART Does Reduce Viral Reservoir Implications for HIV Cure Slide 28 of 55

Wasn’t There Something at ID Week on Ois? • Beta D Glucans • Co-infection of HIV and COVID 19 • But at other meetings and venues…. Slide 29 of 55

ARS Question 2 • Which of the following is a preferred regimen for prevention of latent TB in PLWH who are IGRA or PPD positive and who have not been previously treated (ignoring drug-drug interactions!) 1) INH PO x 6 -9 months 2) Rifampin PO x 4 months 3) 1 HP (Daily INH and Rifapentine for 30 days) 4) 3 HP (INH and Rifapentine Weekly for 3 months) Slide 30 of 55

Preferred TB Prophylaxis Regimens For PLWH • 3 HR Daily (90 Doses) ▫ Isoniazid PO plus rifampin PO daily 3 Months (AI) • 3 HP Weekly (12 Doses) ▫ Rifapentine PO once weekly plus ▫ Isoniazid PO once weekly plus ▫ pyridoxine once weekly 3 Months (AI) Phase 3 trials did not include ART Rifapentine is only recommended for patients receiving an efavirenz-, raltegravir-, or dolutegravir-based ART regimen • 4 R ▫ Rifampin PO Daily Slide 31 of 55 4 Months

Alternative Regimens TB Prophylaxis • 9 H ▫ Isoniazid PO Daily 6 -9 Months (AII) • 4 R* ▫ Rifampin PO Daily 4 months (BI) • 1 HP ▫ Isoniazid qd plus rifapentine PO qd plus pyridoxine PO Daily 4 weeks (BI) Slide 32 of 55

Why Not Recommend 1 HP For PLWH? “BRIEF” TRIAL (ACTG 5279) • INH QD x 9 months vs 1 HP (Rifapentine plus INH QD) x 1 Month • Setting ▫ High endemic TB areas, ▫ All HIV: high CD 4 (median 470), 50% on ART ▫ 21% TST positive ▫ Endpoints: Confirmed or probably TB, Death due to TB, Death of ? Cause • 1 HP was Non Inferior with higher adherence ▫ (97% vs 90% completion) • Concerns Leading to “Alternative” ▫ Number at risk low ▫ Event rate low ▫ Only 50% on ART (mostly efavirenz or nevirapine) • Not Currently Preferred…. But…Will Next Guideline Change? ▫ Only use with Evavirenz at this time ---Dolutegravir and 1 HP in progress Slide 33 of 55

HIGH-DOSE RIFAPENTINE WITH OR WITHOUT MOXIFLOXACIN FOR SHORTENING TREATMENT OF TUBERCULOSIS Slide 34 of 55

S 31/A 5349: 34 clinical research sites, 13 countries TBTC Sites ACTG Sites Slide 35 of 55

S 31/A 5349 Interventions All Rx 7 days/week rifapentine 1200 mg qd moxifloxacin 400 mg qd 2 HRZE / 4 HR “Control” 2 HPZE / 4 HP “RPT” 2 HPZM / 4 HPM “RPT-MOX” 0 Slide 36 of 55 8 week 17 26

S 31/A 5349 Interventions All Rx 7 days/week rifapentine 1200 mg qd moxifloxacin 400 mg qd 2 HRZE / 4 HR “Control” NON-INFERIOR No 2 HPZE / 4 HP “RPT” Yes 2 HPZM / 4 HPM “RPT-MOX” 0 Slide 37 of 55 8 week 17 26

Consolidation Therapy for HIV Associated Cryptococcal Meningitis Slide 38 of 55

Therapy of Cryptococcal Meningitis Liposomal Ampho B plus Flucytosine 3 -4 mg/kg qd 25 mg/kg QID Fluconazole 400 mg po qd Fluconazole 200 mg po qd Slide 39 of 55 2 weeks 8 weeks ≥ 52 weeks**

Therapy of Cryptococcal Meningitis Liposomal Ampho B plus Flucytosine 3 -4 mg/kg qd 25 mg/kg QID Fluconazole 400 mg po qd Fluconazole 200 mg po qd Slide 40 of 55 2 weeks 8 weeks ≥ 52 weeks**

What Is Optimal Dose For Consolidation • Positive CSF culture after 2 weeks of Ampho/5 FC correlates with treatment failure and IRIS ▫ (Vander horst NEJM 1997) ▫ (Chang, AIDS 2013) • Often don’t know results of 2 week LP culture for 1 week • Fluconazole is fungistatic at 400 mg, not fungicidal ▫ Higher doses/levels have some fungicidal activity ▫ (Bicanic CID 2007) • When Fluconazole 800 mg is used for consolidation ▫ Positive culture at 2 weeks does NOT correlate with outcome ▫ Less IRIS ▫ (Boulware) Slide 41 of 55

Consolidation Therapy for HIV Related Cryptococcal Meningitis • Should consolidation therapy dose of fluconazole be increased from 400 mg qd to 800 mg qd ▫ Recommendation may change ▫ Fluconazole well tolerated at both doses ▫ Likely impact on outcome in US is low ▫ Unclear what next revision of OI Guideline will recommend! Slide 42 of 55

Question-and-Answer Session