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PrEP Beyond Pills: New Technologies in Biomedical HIV Prevention

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PrEP
Beyond
Pills
New Technologies in Biomedical HIV Prevention
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As of 1 Oct 2018, Dr. Hurt receives salary support for supervising UNC site activities in a Gilead-funded study of PrEP (DISCOVER).

Dr. Hurt is supported by the Centers for Disease Control and Prevention (ELC-2017-J3), Health Resources and Services Administration (HRSA-17-039, U1OHA30535), the National Institute on Drug Abuse (UH3DA044823), and the National Institute of Allergy and Infectious Diseases (P30AI50410, UM1AI069423, UM1AI068619, UM1AI068614).
The views expressed are not necessarily those of CDC, HRSA, or the NIH.
Christopher B. Hurt, MD
Associate Professor of Medicine
Director, North Carolina HIV Training & Education Center
Site PI, Ryan White HIV/AIDS Program Part D, UNC ID Clinic
Co-Leader, UNC CFAR Collaborative HIV Epidemiology & Prevention Scientific Working Group

Institute for Global Health & Infectious Diseases
University of North Carolina at Chapel Hill
School of Medicine
18 September 2020
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List three ways in which pre-exposure prophylaxis (PrEP) may be delivered in the future.
Describe the results of HPTN 083 and what this means for PrEP in the near term.
Identify the agent currently under investigation as implantable PrEP.
Explain how broadly neutralizing antibodies work to prevent HIV infections.
Objectives
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Pregnancy Prevention
HIV Prevention
Education & behavior modification
Education & behavior modification
Condoms
Condoms
Rings
Rings
Birth control pill & injection
PrEP (oral & injectable)
"Morning-after pill"
Post-exposure prophylaxis
Spermicide
Topical microbicides
Implantable birth control
Broadly neutralizing AbsImplantables
Vasectomy/Tubal Ligation
Vaccination
Adapted from HPTN
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Pregnancy Prevention
HIV Prevention
Education & behavior modification
Education & behavior modification
Condoms
Condoms
Rings
Rings
Birth control pill & injection
PrEP (oral & injectable)
"Morning-after pill"
Post-exposure prophylaxis
Spermicide
Topical microbicides
Implantable birth control
Broadly neutralizing AbsImplantables
Vasectomy/Tubal Ligation
Vaccination
Adapted from HPTN
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Pregnancy Prevention
HIV Prevention
Education & behavior modification
Education & behavior modification
Condoms
Condoms
Rings
Rings
Birth control pill & injection
PrEP (oral & injectable)
"Morning-after pill"
Post-exposure prophylaxis
Spermicide
Topical microbicides
Implantable birth control
Broadly neutralizingImplantables
Vasectomy/Tubal Ligation
Vaccination
Adapted from HPTN
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Rings
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ASPIREMonthly dapivirine (DPV) ring
2629 cisgender women aged 18-45Malawi, South Africa, Uganda, Zimbabwe
July 2012 August 2015
Baeten JM, et al. N Engl J Med. 2016;375(22):2121-2132
27%
lower incidence overall71 infections on DPV, 97 on placebo(95%CI: 1, 46)
61%
lower incidence among participants 25 years old(95%CI: 32, 77)
56%
lower incidence among participants > 21 years old(95%CI: 31, 71)
Younger women didn't adhere
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The Ring StudyMonthly dapivirine ring
1959 cis women aged 18-45South Africa and Uganda
April 2012 December 2016
31%
lower incidence overall77 infections on DPV, 56 on placebo(HR 0.69; 95%CI: 0.49, 0.99)
37%
lower incidence among participants > 21 years old(HR 0.63; 95%CI: 0.41, 0.97)
15%
lower incidence among participants 21 years old(HR 0.85; 95%CI: 0.45, 1.60)
Nel A, et al. N Engl J Med. 2016;375(22):2133-2143
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Open-label extensionsASPIRE HOPE
Ring DREAM
Placebo incidence is estimated
39%
lower incidence
among 1465 open-label recipients in HOPE(95%CI: 14, 65)
63%
lower incidence among 941 open-label recipients in DREAM(95%CI: 0.86, 2.33)
https://www.prepwatch.org/nextgen-prep/dapivirine-vaginal-ring/
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Where does dapivirine go from here?
Positive opinion from European Medicines Agency in July 2020
FDA application anticipated in 2020
Three-month version in development
Coformulation with levonorgestrel in development
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Long-Acting Injectables (LAIs)
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HPTN 083 & 084
Oral FTC/TDF vs Injectable Cabotegravir-LA
MSM & TGW (083) and Cisgender Women (084)

HPTN 083
Oral FTC/TDF vs Injectable CAB-LA for men who have sex with men (MSM) & transgender women (TGW)
4566
at-risk persons(target N = 5000)
87.5% MSM 12.4% TGW
50%
daily FTC/TDF(n=2284)
50%
long-acting injected cabotegravir
(n=2282)
Landovitz RJ, et al. AIDS 2020. Abstract OAXLB01
December 2016 May 2020
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median age(IQR 22-32)
37%
from US(n=1698)
49.7%
of US participants were Black
(n=844)
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HPTN 083Oral FTC/TDF vs Injectable CAB-LA for MSM & TGW
Landovitz RJ, et al. AIDS 2020. Abstract OAXLB01
47 (2.2%) of CAB participants permanently discontinued due to an adverse effect of an injection
Severity of an injection site reaction was strongly associated with odds of permanently discontinuing
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HPTN 083Oral FTC/TDF vs Injectable CAB-LA for MSM & TGW
Landovitz RJ, et al. AIDS 2020. Abstract OAXLB01
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What if you could just remove it?
Kovarova M, Benhabbour SR, et al. Nat Commun. 2018;9(1):4156.
S. Rahima Benhabbour, PhDand Martina Kovarova, PhD
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What if you could just remove it?
Kovarova M, Benhabbour SR, et al. Nat Commun. 2018;9(1):4156.
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Implants
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IslatravirFirst-in-class nucleoside reverse transcriptase translocation inhibitor NRTTIFormerly known as MK-8591
Two mechanisms of action
https://www.natap.org/2019/EACS/EACS_81.htm
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Islatravir PO once weekly protects macaques
Markowitz M, et al. J Infect Dis. 2020;221(9):1398-1406
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Islatravir prototype similar to Nexplanon
https://www.sfaf.org/collections/beta/islatravir-a-potential-prep-hiv-dr...
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Islatravir levels predicted to last 1 year
Matthews RP, et al. IAS 2019 Mexico City. Abstract TUAC0401LB
http://programme.ias2019.org/Programme/Session/167
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bnAbs
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http://www.hvtn.org/en/science/HVTN-studies/AMPstudy.html

Image from: https://www.scripps.edu/news-and-events/press-room/2019/20190710-burton-...

Image from: https://www.scripps.edu/news-and-events/press-room/2019/20190710-burton-...

Breadth & potency of bnAbs are important
How many viruses circulating in transmission networks will the antibody neutralize?
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Breadth & potency of bnAbs are important
How many viruses circulating in transmission networks will the antibody neutralize?
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Breadth & potency of bnAbs are important
How many viruses circulating in transmission networks will the antibody neutralize?
How much of an antibody "dose" is required to neutralize viruses?
Very potent
Not potent
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Open circle: 1st generation mAbCD4 binding siteHigh-mannose patch
Filled circle: 2nd generation mAbApex-specificgp120-gp140 interface
Membrane proximal external region (MPER)
Breadth & potency of bnAbs are important
Burton DR, Hangartner L. Annu Rev Immunol. 2016;34:635-659
Increasing breadth
Increasing potency
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Four bnAbs are the focus of current studies
Burton DR, Hangartner L. Annu Rev Immunol. 2016;34:635-659
Open circle: 1st generation mAbCD4 binding siteHigh-mannose patch
Filled circle: 2nd generation mAbApex-specificgp120-gp140 interface
Membrane proximal external region (MPER)
Increasing breadth
Increasing potency
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Antibody-Mediated Prevention Study (VRC01)

Questions?

Please email me!

Christopher Hurt, MD

[email protected]
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