The UC San Diego AntiViral Research Center sponsors weekly presentations providing the most current research, clinical practices, and trends in HIV, HBV, HCV, TB and other infectious diseases. The slides from an upcoming AIDS Clinical Rounds presentation are intended for educational purposes of the audience and may not be used without the presenter's permission.

1. The UC San Diego AntiViral Research Center sponsors weekly
presentations by infectious disease clinicians, physicians and
researchers. The goal of these presentations is to provide the most
current research, clinical practices and trends in HIV, HBV, HCV, TB
and other infectious diseases of global significance.
The slides from the AIDS Clinical Rounds presentation that you are
about to view are intended for the educational purposes of our
audience. They may not be used for other purposes without the
presenter’s express permission.
AIDS CLINICAL ROUNDS

2. What%can%we%learn%from%
measles?%
Davey&Smith&
and&
Antoine&Chaillon&
No#New#HIV#Infec,ons#

3. State&of&the&Epidemic&
We&are&already&2&years&and&239&days&
behind.&
“1&December&2012&World%AIDS%
Day%2012:%Ge<ng%to%Zero”&

4. Are%the%number%of%people%living%with%HIV%in%
the%US?%
1. Going&up&
2. Going&down&
3. Staying&steady&

5. Are%the%number%of%new%HIV%infecHons%in%the%
US?%
1. Going&up&
2. Going&down&
3. Staying&steady&

6. Where&
are&we?&

7. • 1.1&million&people&in&the&United&States&are&
living&with&HIV.&&
• 1&in&5&are&unaware&of&their&infecKon.&
&

8. We&Are&Here&
Time&
HIV&Incidence&
• The&incidence&of&HIV&infecKon&has&remained&stable&for&the&past&decade&with&an&esKmated&
50,000&new&infecKons&each&year.&
• ANer&30&years&of&research,&there&is&sKll&no&globally&effecKve&HIV&vaccine&or&cure.&&&

9. Principles&of&Epidemic&Control&
f(x)=1/x&

10. What%proporHon%of%suscepHble%people%in%a%
populaHon%need%to%be%protected%(vaccinaHon/%
PrEP)%if%the%R0%of%HIV%in%the%community%is%4?%
1. 1/4&
2. 1/2&
3. 3/4&
4. 4/4&

11. • Ro%=%C%*%P%*%D%
&
• C&=&the&number&of&contacts&the&infecKous&
person&makes&per&day,&week,&month,&etc.&
• P&=&the&probability&of&transmission&per&contact&
with&the&infecKous&person.&
• D&=&the&duraKon&that&the&infected&person&is&
infecKous&to&others.&
Arrrhhh%Not!%
&doing&math&

12. Ro%=%C%*%P%*%D&
Disease% Ro%%
(#%of%usual%secondary%
transmissions)%
Diphtheria& 6Y7&
Measles& 12Y18&
Mumps& 4Y7&
Pertussis& 12Y17&
Polio& 5Y7&
Rubella& 6Y7&
Smallpox& 5Y7&
hp://pracKce.sph.umich.edu/micphp/epicentral/basic_reproduc_rate.php&
The&basic&reproducKon&rate&(R0)&is&the&number&of&secondary&infecKons&
produced&by&a&typical&source&infecKon&in&a&completely&suscepKble&populaKon.&
Fine P et al. Clin Infect Dis. 2011;52:911-916

13. Transmission of an infection with a basic reproduction
number R0!=!4.
Fine P et al. Clin Infect Dis. 2011;52:911-916
© The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases
Society of America. All rights reserved. For Permissions, please e-mail:
journals.permissions@oup.com.

14. Fine P et al. Clin Infect Dis. 2011;52:911-916
© The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases
Society of America. All rights reserved. For Permissions, please e-mail:
journals.permissions@oup.com.
Ro%=%C%*%P%*%D&
Disease% Ro%(#%of%usual%
secondary%
transmissions)%
Herd%Immunity%
Diphtheria& 6Y7& 85%*&
Measles& 12Y18& 83Y94%&
Mumps& 4Y7& 75Y86%&
Pertussis& 12Y17& 92Y94%&
Polio& 5Y7& 80Y86%&
Rubella& 6Y7& 83Y85%&
Smallpox& 5Y7& 80Y85%&

15. Current&Efforts&

16. Where&do&we&need&to&go?&
HIV&R0&=&2Y5&
Herd&
Immunity&
needs&to&be&
40Y80%&
Fine P et al. Clin Infect Dis. 2011;52:911-916
Where&
are&we?&

17. Ro%=%C%*%P%*%D&
• C=%the&number&of&contacts&the&infecKous&person&
makes&per&day,&week,&month,&etc.&
– Sexual&budget:&how&much&sex&does&a&person&have&in&a&
pay&period?&
– Sharing&needles:&how&many&Kmes&does&a&person&share&
needles&with&IV&drug&use?&
– Concurrency:&Is&this&even&a&thing?&
&

18. Serial&Monogamy&vs.&Concurrency&

19. Serial&Monogamy&vs.&Concurrency&
Round%1%

20. Serial&Monogamy&vs.&Concurrency&
Pu<ng%the%
Serial%in%
Monogamy%

21. Serial&Monogamy&vs.&Concurrency&
Round%2%

22. Serial&Monogamy&vs.&Concurrency&
Round%2%

23. Ro%=%C%*%P%*%D&
• P=%the&probability&of&transmission&per&contact&with&
the&infecKous&person.&
• Behavior&
– Sexual&acts&and&
posiKoning&
– SerosorKng&
– Condom&use&
– Substance&use&
(Methamphetamine)&
&
• Biologic&
– Stage&of&HIV&InfecKon&
– Viral&Load&in&Blood&and&
Genital&SecreKons&
– STIs&
– Male&Circumcision&
– Host&geneKcs&
– AnKretroviral&use&
• PEP,&PrEP,&Microbicides&

24. Stage&of&InfecKon&
23&
Wawer, MJ., et al., JID: 2005

25. Stage&of&InfecKon&
24&
Quinn T, et al., NEJM 2000; Wawer, MJ., et al., JID: 2005
Blood%Viral%Loads%

26. PopulaKon&Aributable&FracKon&of&HIV&
AcquisiKon&due&to&STIs&
Rogngen&JA,&et&al.&STD&2001;&Gray&RH,&et&al.&AIDS&2001;&Freeman&et&al.&STI&2007,&&

27. Male%Circumcision%Offers%Some%ProtecHon%%
to%the%HIV%NegaHve%Man&
Auvert,&et&al.&2005&PLoS&Med;&Wawer&et&al.&Lancet&2009&
The&Messy&Part:&Didn’t&work&to&protect&female&partners&when&the&man&was&HIV+&

28. Tenofovir Vaginal Microbicide (CAPRISA 004)
Q Abdool Karim et al. Science 2010;329:1168-1174

29. Tenofovir/EmcitriHbine%PrEP%
Grant R et al. NEJM 2010
The&Messy&Part:&≈$12,000/year&of&PrEP&&

30. HIV&Vaccine??&
• Four&priming&
injecKons&of&a&
recombinant&
canarypox&vector&plus&
two&boosters&of&a&
recombinant&gp120&
subunit&vaccine.&&
• N=&16,402&healthy&
men&and&women&&
• Heterosexual&risk&
29&RerksYNgarm&et&al.&NEJM&2009&

31. Ro%=%C%*%P%*%D&
Why&is&this&
line&going&
up?&

32. Ro%=%C%*%P%*%D&
• D=%the&duraKon&that&the&infected&person&is&
infecKous&to&others.&
• TesKng&
– Chronic&
– Acute&
• TreaKng&
– Gegng&to&zero&(undetectable)&
– Gardner&Cascade&

33. TesKng&for&Acutes&in&San&Diego&
Projected%
Actual%
In&the&Central&Region&of&San&Diego&the&incidence&of&HIV&infecKon&was&below&projected&
esKmates&in&proporKon&to&the&number&of&individuals&diagnosed&with&acute&infecKon&
since&2007.&The&incidence&in&other&regions&of&San&Diego&remained&constant.&&
Mehta&et&al.&HIV&Dynamics&2014&

34. TesKng&for&Acutes&in&San&Diego&
Projected%
Actual%
No&focused&
tesKng&for&
acute&
infecKons&
In&the&Central&Region&of&San&Diego&the&incidence&of&HIV&infecKon&was&below&projected&
esKmates&in&proporKon&to&the&number&of&individuals&diagnosed&with&acute&infecKon&
since&2007.&The&incidence&in&other&regions&of&San&Diego&remained&constant.&&
Mehta&et&al.&HIV&Dynamics&2014&

35. Cohen MS et al. N Engl J Med 2011;365:493-505
Treatment%as%PrevenHon%(TasP)&

36. HIV&sexual&transmissibility&metaYanalysis:&
Transmission&on&ART&related&to&viral&load&
Aga&S,&et&al.&AIDS&2009&Jul&17;23(11):1397Y404.& 35&

37. Reuben M Granich , Charles F Gilks , Christopher Dye , Kevin M De Cock , Brian G Williams
Universal voluntary HIV testing with immediate antiretroviral therapy as a strategy for elimination of HIV transmission: a mathematical model
The Lancet, Volume 373, Issue 9657, 2009, 48 - 57 http://dx.doi.org/10.1016/S0140-6736(08)61697-9
Treatment%as%PrevenHon%(TasP)&

38. https://www.aids.gov/federal-resources/policies/care-continuum/
Gardner%Cascade&
Gardner E M et al. Clin Infect Dis. 2011;52:793-800
Reducing&DuraKon&of&InfecKousness&:D&&

39. What&rates&of&ART&coverage&do&we&
need&to&reduce&the&HIV&epidemic&
among&MSM&in&San&Diego?&
Currently:&
• Around&56,000&MSM&in&San&Diego&&
• HIV&prevalence&among&MSM&in&San&
Diego&20%&
• ART&Coverage&rate&around&30%&
• Condom&use&around&60%&

40. Need&a&calculator&
PopulaKon&&
CharacterisKcs&

41. PopulaKon&&
CharacterisKcs&
Variables&

42. IntervenKon&parameters&

43. OUTPUT&

44. Nb of Sex Acts with Casual Partners/yr=10 Nb of Sex Acts with Casual Partners/yr=20 Nb of Sex Acts with Casual Partners/yr=30
0
2500
5000
7500
10000
0 5 10 15 0 5 10 15 0 5 10 15
time (years)
NumberofHIVinfectionsaverted(NIA)
30% TasP coverage 40% TasP coverage 50% TasP coverage
*
686 NIA
*
TasP&and&number&of&infecKons&averted&

45. What&rates&of&PrEP&coverage&do&we&
need&to&reduce&the&HIV&epidemic&
among&MSM&in&San&Diego?&
Currently,&PrEP&rates&among&MSM&is&
almost&negligible.&

46. Nb of Sex Acts with Casual Partners/yr=10 Nb of Sex Acts with Casual Partners/yr=20 Nb of Sex Acts with Casual Partners/yr=30
0
2000
4000
6000
0 5 10 15 0 5 10 15 0 5 10 15
time (years)
NumberofHIVinfectionsaverted(NIA)
20% PrEP coverage 30% PrEP coverage 50% PrEP coverage
*
321 NIA
*
481 NIA#
#
PrEP&and&number&of&infecKons&averted&

47. How&much&would&this&cost?&
ART:&$23,000&USD/year&&
PrEP:&$10,300/year&

48. Nb of Sex Acts with Casual Partners/yr=20
0
1000
2000
3000
4000
0 5 10 15
time (years)
CumulativecostofTasPinmillionsofUSD
30% TasP coverage 40% TasP coverage 50% TasP coverage
Nb of Sex Acts with Casual Partners/yr=20
0
1000
2000
3000
0 5 10 15
time (years)
CumulativecostofPrEPinmillionsofUSD
20% PrEP coverage 30% PrEP coverage 50% PrEP coverage
$286 million
*
*
*
$584 million
*
CumulaKve&cost&of&TasP% CumulaKve&cost&of&PrEP%

49. Can&we&make&PrEP&more&
efficient?&
MSM&between&the&ages&of&21&and&52&
years&account&for&90%&of&all&new&
infecKons&in&San&Diego,&but&only&
account&for&43%&of&all&MSM.&

50. 10 20 30 40 50 60 70
0.000.010.020.030.04
Age (year)
Density
GTZ&straKfied&by&age&
• In%Red:%Age&DistribuKon&of&HIVY1&
infected&individuals&
• In%Black:&Age&DistribuKon&of&the&
total&male&populaKon&in&SD&
County&
• 90%&of&the&HIV&cases&Correspond&
to&individuals&between&21&and&52&
yrs&old&
• %AUC90[total&pop]=46.3%&
!in&other&words,&we&have&to&cover&
46.3%&of&individuals&with&PReP&to&
target&90%&of&the&HIV&cases!&

51. Nb of Sex Acts with Casual Partners/yr=20
0
500
1000
1500
2000
0 5 10 15
time (years)
CumulativecostofPrEPIntervention(millionsofUSD)
Non Targeted Age Targeted
Nb of Sex Acts with Casual Partners/yr=20
0
500
1000
1500
2000
0 5 10 15
time (years)
NumberofHIVinfectionsaverted(NIA)
Non Targeted Age Targeted
*
433 NIA
*
#
# 481 NIA
$270 million
$584 million#
*
*
#
30%&PrEP&Coverage&
PrEP&Targeted&on&Age&(between&21&and&52&yrs&old)%

52. Combining&TasP&and&PrEP&

53. Age Targeted PrEP Coverage (NNI)
0% 10% 20% 30% 40% 50%
TasPCoverage
0% 638 598 558 517 477 437
30% 449 421 393 364 336 308
40% 383 359 335 310 286 262
50% 316 296 277 257 237 217
60% 255 239 223 207 191 175
!1!
Cost per infection prevented
$400-500,000
$500-600,000
$600-700,000
$700-800,000
$800-900,000
!1!
In&one&year&we&can&make&a&difference&

54. GtZ&in&SD&
• To&reduce&the&number&of&new&infecKons&in&
San&Diego&by&threeYfourths&in&20&years&would&
require&61%&TasP&coverage&and&50%&PrEP&
coverage&of&MSM&between&the&ages&of&21&and&
52&years.&
• This&would&cost&$1.4&billion&
• InteresKngly,&if&TasP&coverage&was&50%,&then&
the&annual&cost&of&TasP&should&start&to&
decrease&aNer&10&years.&&&&

55. Risk&CompensaKon&
PrEP Coverage
0% 10% 20% 30% 40% 50%
Condomuse
60% 499 464 429 394 359 324
50% 623 580 536 492 449 405
40% 748 696 643 591 538 486
30% 873 811 750 689 628 567
20% 997 927 858 788 718 648
! PrEP Coverage
0% 10% 20% 30% 40% 50%
#ofSexActs
10 249 232 214 197 179 162
15 374 348 322 295 269 243
20 499 464 429 394 359 324
25 623 580 536 492 449 405
30 748 696 643 591 538 486
!
HIV incidence compared to baseline
0.5 to ≤0.75 fold
0.75 to ≤1 fold
1 to ≤1.25 fold
1.25 to ≤1.5 fold
1.5 to ≤2 fold
> 2 fold
!1!
Decrease
Incidence
Increase
Incidence

56. Ro%=%C%*%P%*%D&
• D=%the&duraKon&that&the&infected&person&is&
infecKous&to&others.&
– EliminaHon:&interrupKon&of&endemic&transmission&(R0<1).&
– EradicaHon:&reducKon&of&infecKous&organisms&in&the&
world&to&Zero.&This&would&need&a&cure.&&

57. George&E.&P.&Box&(1976)&Science&and&Sta*s*cs&Journal&of&the&American&Sta*s*cal&
Associa*on,&Vol.&71,&No.&356.&(Dec.,&1976),&pp.&791Y799&
“All%models%are%
wrong,%but%
some%are%
useful.”%%

58. HIV&Test&and&Treat&
PrEP/Microbicide/PEP&
Retain&into&care&
STI&Test&and&Treatment&
Condoms/Clean&Needles&
Circumcision&
Zero&Cascade&
UK&Plan&
• Condoms&
• Behaviour&
change&
• PEP/PREP&
• Microbicides&
• Treatment&
Ro%<1&
?%hp://www.huffingtonpost.com/mehrozYbaig/howYsanYfranciscoYisYgegngYtoYzeroY
onYhiv_b_6290636.html&
SF&Plan&
• PREP&
• Rapid&TesKng&and&
Treatment&
• RetenKon&

59. Thanks&for&your&kind&aenKon&