1. Can We Really End AIDS? Challenges of HIV Prevention and Treatment
Melanie A. Thompson, MD
AIDS Research Consortium of Atlanta
Atlanta, Georgia USA

2. 1981

3. CDC MMWR - June 5, 1991

4. Gay
Related
Immune
Deficiency =
GRID
New York Times - July 3, 1981

5. STIGMA!

6. AIDS
Was 100% Fatal

7. AIDS is the most advanced stage of HIV infection in which the immune system cannot defend against diseases; usually when the CD4 cell count is below 200/mm3

8. We characterize the severity of an HIV infection by talking about the viral load and the CD4 count. The viral load is the amount of virus measured in the blood. The CD4 count is the number of a special type of white blood cell that is attacked by HIV. If you think about developing AIDS as a train wreck, the viral load tells us how fast we are going while the CD4 count tells us how far we are from going off the cliff that we call AIDS. The problem with this analogy is that once you have AIDS, if you take HIV treatment, you may actually reverse the train wreck.

9. To enter a cell, HIV uses the CD4 receptor and a co-receptor, either CCR5 or CXCR4
T-cell surface
Berger EA, et al. Nature. 1998;391:240.

10. HIV Life Cycle NRTI NNRTI Protease Inhibitor (Maturation Inhibitor)
CCR5 Inhibitor
Fusion Inhibitor
(Attachment Inhibitor)
(Anti-CD4 Monoclonal Ab)
Protease Inhibitor
(Maturation Inhibitor)
Integrase Inhibitor
NRTI
NNRTI

11. Antiretroviral Therapy 2017
NRTIs
Zidovudine (AZT, ZDV)
Lamivudine (3TC)
Didanosine (ddI)
Zalcitabine (ddC)
Stavudine (d4T)
Emtricitabine (FTC)
Tenofovir (TDF or TAF)
Abacavir (ABC)
NNRTIs
Nevirapine (NVP)
Delavirdine (DLV)
Efavirenz (EFV)
Etravirine (ETR)
Rilpivirine (RPV)
Entry inhibitors
Enfuvirtide (T20)
Maraviroc (MVC)
Integrase inhibitors
Raltegravir (RAL)
Elvitegravir (ELV)
Dolutegravir (DTG)
Protease inhibitors
Saquinavir HG (SQV-HG)
Saquinavir SG (SQV-SG)
Indinavir (IDV)
Ritonavir (RTV, r))
Nelfinavir (NFV)
Amprenavir (AMP)
Fosamprenavir (f-AMP)
Tipranavir (TPV)
Lopinavir/r (LPV/r)
Atazanavir (ATV)
Darunavir (DRV)
Fixed Dose Combos
AZT+3TC
ABC+3TC
AZT+3TC+ABC
FTC+TDF
EFV+TDF+FTC
RPV+FTC+TDF
ELV+COBI+FTC+TDF
DTG + ABC + 3TC
ELV+COBI+FTC+TAF
DRV+COBI
ATV+ COBI
RPV+FTC+TAF
FTC+TAF
DTG + RPV
PK Booster
Cobicistat (COBI)
These are all of the drugs that have been approved to fight HIV over the years. We have made remarkable progress.

12. Antiretroviral Therapy 2017
NRTIs
Zidovudine (AZT, ZDV)
Lamivudine (3TC)
Emtricitabine (FTC)
Tenofovir (TDF or TAF)
Abacavir (ABC)
NNRTIs
Efavirenz (EFV)
Etravirine (ETR)
Rilpivirine (RPV)
Entry inhibitors
Enfuvirtide (T20)
Maraviroc (MVC)
Integrase inhibitors
Raltegravir (RAL)
Elvitegravir (ELV)
Dolutegravir (DTG)
Protease inhibitors
Ritonavir (RTV, r))
Lopinavir/r (LPV/r)
Atazanavir (ATV)
Darunavir (DRV)
Fixed Dose Combos
AZT+3TC
ABC+3TC
FTC+TDF
EFV+TDF+FTC
RPV+FTC+TDF
ELV+COBI+FTC+TDF
DTG + ABC + 3TC
ELV+COBI+FTC+TAF
DRV+COBI
ATV+ COBI
RPV+FTC+TAF
FTC+TAF
DTG + RPV (NEW!)
PK Booster
Cobicistat (COBI)
Mainly, however, we use a smaller number of drugs as we have eliminated those that are too toxic and we favor those that combine two or more drugs in one tablet, for simplicity.

13. 2017

14. 1

15. There is Good News in the Fight Against HIV!

16. With Care and Treatment, People With HIV Can Live a Near Normal Life Span, Without Progression to AIDS!

17. No One Should Die of AIDS in 2017!

18. 2

19. Even Without A Vaccine, HIV Infection is Preventable!
HIV treatment IS HIV prevention
PrEP/PEP can prevent HIV

20. Treatment IS Prevention!

21. 67.5%
Reduction in
HIV Infection P=

22. HPTN-052 Eshleman SH, IAS 2015 MOAC0106LB
1763 serodifferent heterosexual couples randomised to immediate or deferred ART
75 HIV infections
7 confirmed to be linked to a seropositive partner receiving ART
4 occurred before partner was virally suppressed
3 occurred during virologic failure
NO infections from virally suppressed partner

23. PARTNER Study Rodger A, JAMA 2016;316(2)
Heterosexual and male same sex couples having sex without condoms, where the HIV-positive partner had HIV-1 RNA ≤ 200 c/mL.
888 couples
58,000 condomless sex acts
11 HIV infections, examined by phylogenetic analysis
NO infections from virally suppressed partner

24. Opposites Attract Study Bavington, et al. IAS 2017, Abstract 5469
Male serodiscordant couples in Australia, Thailand, Brazil
HIV+ partner had undetectable HIV-1 RNA < 200 c/mL
388 couples enrolled (353 couples with ≥ 1 follow up), 591 CYFU
16,888 acts of condomless anal intercourse
NO infections from virally suppressed partner

25. No HIV infections from virally suppressed partners!
75,000 acts of condomless sex
No HIV infections from virally suppressed partners!

26. “…This means that people who take ART daily as prescribed and achieve and maintain an undetectable viral load have effectively no risk of sexually transmitting the virus to an HIV-negative partner.”
US Centers for Disease Control and Prevention 9/27/17

27. Undetectable = Untransmittable

28. Swaziland Highest HIV prevalence in the world = 27%
32% among year olds
Testing and treatment were scaled up dramatically
Viral suppression rose to 73%
HIV diagnoses were decreased by 44%

29. Optimal HIV Treatment and Prevention Requires Continuous Viral Suppression and Continuous Access to Antiretroviral Therapy

30. How Are We Doing?

31. 90%
Italy
72%
59%
90%
80%
82%
European HIV Continuum of Care Working Group. CID 2017;64:12:1644–56

32. We must plug “leaks” in the continuum of care to optimize life expectancy and health outcomes for people living with HIV, and to decrease new infections.

33. 3

34. HIV Testing is the Gateway to Treatment and Prevention
Get Tested!

35. Rapid HIV testing takes as little as 2 to 20 minutes using fingerstick or saliva

36. The Prevention Continuum
Horn T, et al. JIAS 2016, 19:21263

37. Late Diagnosis
55.6% of persons newly diagnosed in Italy have CD4 count < 350 cells/µL1
36.9% have < 200 cells/µL (AIDS)1
How to address late diagnosis?
Make testing free, confidential, safe, and stigma-free
Routine opt-out HIV screening in medical settings
Essential to provide targeted rapid testing for key populations in a community setting where there is trust and stigma is less
Ensure rapid care entry and access to ART
Ensure PrEP to those who test negative, as needed
1 Supplemento del Notiziario dell’Instituto Superiore Sanità at

38. Verona: Sialon II City Profile - MSM
Sialon II City Profile: available at

39. Verona: Sialon II City Profile - MSM
Sialon II City Profile: available at

40. 4

41. Pre-exposure Prophylaxis (PrEP) Preventing HIV Until the Vaccine Arrives..

43. Tenofovir Disoproxil Fumarate/Emtricitabine (TDF/FTC; Truvada®)
Tenofovir Disoproxil Fumarate is an orally bioavailable prodrug of tenofovir.
Tenofovir contains a phosphonate, it is an analog of AMP and is therefore a nucleotide reverse transcriptase inhibitor. This is the first nucleotide for the treatment of HIV.
As a nucleotide, tenofovir DF has several distinct characteristics. Dosed as one tablet, once daily, with food, tenofovir DF is easy to administer and may help patients comply with their treatment. Tenofovir DF also has a distinct and favorable resistance profile showing durable activity against otherwise nucleoside resistant viruses.
The unique resistance profile of tenofovir DF is evident from cross resistance studies.
Approved 2012 by US Food and Drug Administration
for the prevention of HIV infection

44. Randomized, Placebo-Controlled Daily PrEP Efficacy Trials
Trial (Sponsor)
Sample Size
Intervention vs. Placebo
Population
Location
iPrEx
(NIH; Gates)
n=2499
Oral TDF/FTC
MSM, transgender women
Peru, Ecuador,
S Africa, Brazil, Thailand, US
Partners PrEP
(Gates)
n=4747 couples
Oral TDF
Heterosexual serodiscordant couples
Kenya,
Uganda
TDF2
(CDC) n=1200
Sexually active adults
Botswana
Bangkok Tenofovir
(CDC) n=2413
Injection drug users
Thailand
FEM-PrEP
(USAID, Gates, FHI 360)
n=1951
Heterosexual women
S Africa,
Tanzania
VOICE
(MTN-003)
n=5029
Vag 1% tenofovir gel
Uganda,
Zimbabwe
Grant et al. NEJM 2010; 363 :2587‐ 2599
Baeten et al NEJM 2012;367: ;CROI 2014: Abstract 43
Thigpen, et al. NEJM 2012;367:423-34
Grant et al. NEJM 2010; 363 :2587‐ 2599
Baeten et al NEJM 2012;367: ;CROI 2014: Abstract 43
Thigpen, et al. NEJM 2012;367:423-34
Choopanya et al. Lancet 2013 Jun 15;381(9883):
Van Damme, et al. NEJM. 2012;367:411-22
Marazzo et al. CROI 2013: Abstract 26LB
Choopanya et al. Lancet 2013 Jun 15;381(9883):
Van Damme, et al. NEJM. 2012;367:411-22
Marazzo et al. CROI 2013: Abstract 26LB

45. Relative Risk Reduction (95% CI)
Results of Randomized, Placebo-Controlled Daily PrEP Efficacy Trials Detection of Tenofovir Levels in Blood Is Associated with Greater Efficacy
Study
Oral Regimen
Dosed Daily
Relative Risk Reduction (95% CI)
All Subjects
Drug Detectable
iPrEx
TDF/FTC
0.44 ( )
0.92 (0.40 – 0.99)
Partners
PrEP
TDF
0.67 (0.44 – 0.81)
0.75 (0.55 – 0.87)
TDF vs TDF/FTC not significantly different
0.86 (0.67–0.94)
0.90 (0.58–0.98)
Bangkok
Tenofovir
0.49 (0.10 – 0.72)
0.74 (0.17–0.94)
% Pts with Detectable Drug
TDF2
0.62 (0.22 – 0.83)
50% among HIV infected
80% among not infected
Table adapted from Hendrix, C. HIV Pre-Exposure Prophylaxis: Clinical Pharmacology Insights. CROI 2014, Oral Abstract 61
Baeten et al. CROI 2014: Abstract 43
Hendrix C. Cell 2013:155:
van der Straten, et al. CROI 2014: Abstract 44
Snapinn S, Chen Mg, Jiang Q et al. Pharm Stat Oct-Dec;5(4):
Table adapted from Hendrix, C. HIV Pre-Exposure Prophylaxis: Clinical Pharmacology Insights. CROI 2014, Oral Abstract 61
Baeten et al. CROI 2014: Abstract 43
Hendrix C. Cell 2013:155:

46. Results of Randomized, Placebo-Controlled Daily PrEP Efficacy Trials
Study
Oral Regimen
Dosed Daily
Relative Risk Reduction (95% CI)
All Subjects
Drug Detectible
FEM-PrEP
TDF/FTC
Stopped due to futility
< 40% among all participants
VOICE
TDF
Showed no efficacy
< 30% among all participants
Poor adherence, as measured by detectable drug levels, was a major factor in lack of efficacy in both studies
Self reported adherence was very high and was not predictive of outcome except when patients said that they did not take drug
Table adapted from Hendrix, C. HIV Pre-Exposure Prophylaxis: Clinical Pharmacology Insights. CROI 2014, Oral Abstract 61
Baeten et al. CROI 2014: Abstract 43
Hendrix C. Cell 2013:155:
van der Straten, et al. CROI 2014: Abstract 44
Snapinn S, Chen Mg, Jiang Q et al. Pharm Stat Oct-Dec;5(4):
Van Damme, et al. NEJM. 2012;367:411-22
Marazzo et al. CROI 2013: Abstract 26LB

47. PROUD McCormack S et al. Lancet, Vol 387; January 2, 2016
Open label randomized trial of immediate v deferred TDF/FTC for men having condomless anal sex
544 participants
Safety: 28 adverse events: nausea, HA, arthralgia; none serious
23 HIV infections: 3 immediate, 20 deferred
86% reduction in infections (p=0.0001)

48. Effectiveness of “on demand” PrEP Randomized placebo-controlled trial
Ipergay Study Design
Effectiveness of “on demand” PrEP
Randomized placebo-controlled trial
High risk MSM
Condomless anal sex with > 2 partners within 6 m
eGFR > 60 mL/mn
Full prevention services* TDF/FTC before and after sex (n=950)
Full prevention services* placebo before and after sex (n=950)
Counseling, testing for STI, condoms, vaccination, PEP
Primary endpoint : HIV infection
Incidence of HIV-infection: 3%PY, 50% efficacy, 64 events
~ 2000 pts 48

49. Ipergay : Event-Driven iPrEP
1 tablet (Truvada®/placebo) 24 hours later
1 tablet (Truvada®/placebo) 48 hours later
2 tablets (Truvada®/placebo) hours before sex
Friday
Saturday
Sunday
Monday
Tuesday
Wednesday
Thursday

50. IPERGAY Results Molina J et al. N Engl J Med 2015;373:2237-46
400 men gay/bisexual men
Median 15 pills per month; 86% detection of drug in TDF/FTC arm
Safety: Gastrointestinal side effects (9% above placebo); renal (8% above placebo)
16 HIV infections: 2 TDF/FTC, 14 placebo;
86% reduction in infections (p=0.002)

51. TDF/FTC for prevention of HIV (with adequate adherence): 86-99%5-7
Comparative Efficacy
Influenza vaccine, 2017: 48%1
Statins for prevention of heart attack: 64%2
Zoster vaccine for prevention of shingles: 51%3
Seat belts for prevention of fatalities: 50%4
TDF/FTC for prevention of HIV (with adequate adherence): 86-99%5-7
1 Flannery B, et al. MMWR 2017;66:167–171.
2 Tonelli M, et al. CMAJ Nov 8; 183(16): e1189–e1202.
3 Oxman N, et al. N Eng J Med 2005;352:
4 Kahane, C. National Highway Traffic Safety Administration; DOT-HS
5 Molina J et al. N Engl J Med 2015;373:
6 McCormack S et al. Lancet, Vol 387; January 2, 2016.
7 Anderson P, et al. Science Translational Medicine  12 Sep 2012: 4(151), pp. 151ra125.

52. PrEP Works!

53. Safety of TDF-Based PrEP in Clinical Trials
Most common side effects are gastrointestinal, especially nausea, but they are usually of short duration
Few persons experience kidney side events
Small decreases in bone mineral density that occurs slowly over time, but no increase in fractures
No pregnancy complications due to drug
Grant et al. NEJM 2010; 363 :2587‐ 2599
Thigpen, et al. NEJM 2012;367:423-34
Van Damme, et al. NEJM 2012;367:411-22
Groshkopf et al. JAIDS 2013;64:79–86
Baeten et al NEJM 2012;367:
Groshkopf et al. JAIDS 2013;64:79–86
Baeten et al NEJM 2012;367:

54. A PrEP Protocol is Needed

56. Barriers to PrEP Awareness: community and provider Lack of access
Providers must be educated & willing to prescribe
Drug availability: generic TDF/FTC in Italy!
Biases: “Just use condoms”; shame about sex
Fears
Community: Medication side effects
Providers: Increase in condomless sex and STIs; lack of knowledge about PrEP
Stigma: from community and providers

57. PEP = Postexposure Prophylaxis

58. PEP
4 weeks of a full 3 drug antiretroviral regimen AFTER a significant exposure to HIV
Should be started as soon as possible, preferably within 72 hours of exposure (<4h EACS)
HIV test should be done
In 6 studies, 3% got HIV in spite of PEP; 0.5% true PEP failures
PEP is very effective
CDC, 2016:

59. Persons on PEP should be evaluated for PrEP
PEP = A Bridge to PrEP
Persons on PEP
should be evaluated for PrEP

60. 5

61. Eliminate Stigma! Stigma Kills - Don’t Tolerate It!
Eliminate stigmatizing policies such as HIV criminalization
Require meaningful involvement of PLWH in all programs

62. Internalized Stigma is Associated with Poor Health Outcomes
Southern AIDS Strategy Initiative. HIV Stigma Study in the Deep South: Descriptive Findings. August,

63. Other Effects of Stigma
Reluctance to be tested
Fear of disclosure to family, friends, work
Reluctance to begin lifesaving medications that might disclose HIV status
Poorer health outcomes

64. Verona: Sialon II City Profile - MSM
Sialon II City Profile: available at

65. Better education of the general public
Greater responsibility and better education of mass media
Better teaching in schools
Greater visibility of people open abt HIV
Legislation to reduce discrimination
Greater activity on social media, groups and forums to educate/counter negativity
Better training of healthcare professionals
Greater activity for HIV patient groups
None, I do not see a need
Murungi A,et al. IAS 2017; WEPED1423

66. 6

67. Ending AIDS Requires A Plan!
is a Goal – Not A Plan!

68. Fulton County, GA (Atlanta) Strategy to End AIDS
Task Force on HIV/AIDS created by county Board of Commissioners
Produced 3 reports from June, July 2017
Goals, objectives, actions
10 key priorities

69. Key Elements of Planning
Involve people with HIV & key populations in all phases of planning, execution, and monitoring
Be inclusive about participants
Consumers, care providers (medical, mental health, substance use), clinic administrators, community organizations, government officials, researchers & epidemiologists, educators, religious leaders, etc.
Know your epidemic: be data-driven
Hold listening sessions – and LISTEN!
Identify the biggest areas needing improvement
Develop consensus-driven goals, objectives and actions
Assign metrics, establish baselines, reevaluate

70. Can We Really End AIDS? Yes, because…
People whose HIV is appropriately treated can live a near normal lifespan and never progress to AIDS
HIV infection is preventable
Treatment
PrEP & PEP
Clean injecting equipment

71. Can We Really End AIDS? BUT…
It will require collaboration of all sectors, including meaningful involvement of persons living with HIV
It will require addressing stigma
It will require political will
It will require an implementation plan

72. Every Diagnosis of AIDS is Avoidable in 2017
Every Death from AIDS
is a
Failure of Public Health

73. Every New HIV Infection is Preventable in 2017

74. We can bend the epidemic curve toward zero but do we have the political will to do so?

75. The Answer is In YOUR Hands

76. The Most Important Lesson of the Day…

77. Silence (Still) Equals Death
Find Your Voice and Use It!