1. Biomedical Interventions and Risk Compensation
Jean-Michel Molina
Saint-Louis Hospital, University of Paris Diderot,
ANRS (National Agency for AIDS Research)
Inserm U941, Paris, France
STI 2018
Understanding and Adressing the HIV and STI syndemics
Amsterdam, July 21-22, 2018 1

2. Disclosures Advisory boards: Gilead, Merck, ViiV, Teva Grants: Gilead
Stock: none

3. Biomedical Interventions to Prevent HIV-Infection
Condoms
Male Circumcision
Post-Exposure Prophylaxis (PEP)
Treatment of HIV-infection (TASP)
Pre-Exposure Prophylaxis (PrEP)
Vaccine

4. Risk Compensation
Critical issue in the public health implementation of biomedical interventions: Could increased risky sexual behavior counteract the biological efficacy against HIV?
Risk management plan: Assess the public health impact of PrEP
Risk compensation: Adjustment of behavior in response to a perceived reduction in risk
Behavioral adaptation: Behavioral changes triggered by a safety measure: reduction in condom use
Behavioral disinhibition: Lack of restraint with more risk taking behaviors: increasing Nb of partners, Nb of sexual acts, chemsex…
STIs: Best objective measure of risk compensation and most feared consequence of risk compensation
Individual vs. population impact of biomedical interventions: risk compensation among people not using PrEP/TASP
Cassell BMJ 2006

5. PEP and Changes in Sexual Behavior
76%
85%
397 adults (92% MSM) enrolled in a PEP study in SF with 4 weeks of PEP and 5 counseling sessions
Over 12 months of follow-up significant reduction in condomless sex and no increase in STIs rates
17% needed an another course of PEP
4 HIV seroconversion, 3 in MSM with an HIV incidence of 1.2/100 PY
Martin JN et al. AIDS 2004

6. Effect of Antiretroviral Therapy on Sexual Behavior
Unprotected sex lower in pts on ART vs no ART OR: 0.73 (95%CI: )
STI diagnoses lower in pts on ART vs no ART OR: 0.58 (95% CI: )
No change in injection risk-taking behavior (OR: 0.90 (95% CI: )
Doyle JS. Et al CID 2014

7. Condomless Sex with HIV Negative (or unknown status) Partners in
MSM
IMM ART
(N=1314)
DEF ART
(N=1306)
P Value
Heterosexual
(N=1012)
(N=1053) P
Value
Baseline
19.8%
20.0%
13.2%
11.7%
12 mths
12.7%
13.1%
0.76
10.8%
8.3%
0.066
24 mths
16.3%
14.7%
0.32
9.5%
5.6%
0.004
CLS-D declined over time in both arms
CLS-D did not differ in MSM by randomisation arm at 12 or 24 months
CLS-D in heterosexuals at 24 months higher with immediate ART
Rodger A et al. Presented at AIDS 2016, Durban
$Baseline 2 estimates exclude those diagnosed less than 3 months before completing the baseline TRB CRF, who may be reporting pre-diagnosis sexual behaviour. I
MM ARM =randomised to immediate ART. DEF ARM = randomised to deferred ART. P values by Chi-squared tests.

8. New diagnoses of HIV and STIs from 1996 to 2015 in MSM in England
Figure 10
New diagnoses of HIV and STIs from 1996 to 2015 in MSM in England
Unemo M et al. Lancet Infect Dis 2017

9. PrEP and Risk Compensation
What about PrEP:

10. Condom Use in Ipergay
Proportion Pts with Condomless Sex at Last Receptive Anal Intercourse
P for Trend =
No significant change in median Nb of partners or sexual acts during the open-label phase (p=0.42 and p=0.12)
No significant increase in incidence rate of a first STI
(49 vs 59 per 100 PY in the double-blinded and OLE phases (p=0.11)
Molina et al Lancet HIV 2017

11. Community-Level Changes in Condom use with Casual Partners Among MSM
Figure 11
30% 1%
46%
The Lancet Infectious Diseases  , e235-e279DOI: ( /S (17) )
Holt M. et al . Lancet HIV 2018
Copyright

12. Trends in STIs and HIV Testing and Treatment Uptake among MSM
2013
2014
2015
2016
2017
PrEP use in past 6 months 2% 7%
24%
Any STI in past 12 months
17%
18%
20%
23%
31%
HIV test in past 6 months
59%
65%
66%
72%
77%
HIV+ on ART
79%
86%
87%
90%
94%
HIV+ with VL undetectable
84%
88%
89%
Crystalmet in past 6 months
15%
16%
13%
14%
Increase in PrEP uptake and decrease in condom use coincided with a reduction in new HIV diagnoses in MSM by 16% in Victoria and 11% in NSW
Holt M. et al. Lancet HIV 2018

13. STIs in PROUD - Randomized Phase
Mc Cormack et al Lancet 2015 13

14. PROUD - Post-Randomized Phase
Rate of sexually transmitted infections (STIs)
Randomized phase
Post-randomized phase
Rate (n/100PY)
IMM
DEF
Rectal GC
35.3 (81/229)
33.0 (67/203)
31.4 (129/411)
32.6 (116/356)
Rectal CT
33.6 (77/229)
21.7 (44/203)
33.1 (136/411)
29.8 (106/356)
Syphilis
19.4 (46/237)
13.2 (28/212)
31.1 (132/424)
25.9 (93/359)
The incidence of rectal infections was high in both groups and phases
There was an increase in syphilis in the post-deferred phase
White E et al. IAS Paris, France. Oral #TUAC0101

15. Meta-Analyis of Effect of PrEP on STIs Diagnosis among MSM
Significant increase in any rectal STI diagnosis (OR: 1.39, 95% CI: )
Significant increase in rectal chlamydia (OR: 1.59, 95% CI: )
Increase in STIs rates in more recent studies (OR: 1.47, 95% CI: )
Traeger MW et al. CID 2018

16. Experience from a PrEP Clinic in Paris Prospective Open-label Cohort
Follow-up and HIV incidence
1069 pts came for a first visit from 11/2015 to 05/2017
HIV-infection at first visit n=10 (0.9%)
1049 started PrEP: 75% « On Demand »
486 PY of FU (median follow-up of 5.6 months)
15% lost to FU (changed center, moved, stable couple, other)
4 breakthrough HIV-infection (2 daily) HIV incidence: 0.8/100 PY
Changes in Sexual behavior (from Baseline to Month 12)
Condomless sex at last intercourse increased from 53% to 79%
Modest increase in overall STIs rates from 14.6% to 19.2%
Significant increase in rectal chlamydia or gonorrheal infections (11% to 20.4%, p<10-4)
Noret M. et al. AIDS 2018 (in press)

17. Increase in Rectal Chlamydia Infections in France among MSM before PrEP
Nb rectal chlamydia infections
1600
1400
non L strains
1200
LGV
Non L
1000
LGV
% HIV + 76 36
800
600
400
200
2002
2003
2004
2005
2006
2007
2008
2009
2010
2011
2012
2013
2014
2015
2016
Chlamydia French Reference National Center LGV Network

18. Partners not Condom Use Predicting Factors of STIs
Drive STIs Rates
SPARK: Community-based PrEP demonstration project in NYC
261 MSM followed until M12 after PrEP intitiation
Decrease in condom use: 61% to 46%
Predicting Factors of STIs
aOR
95% CI p
Age < 25 years old
3.67
< 0.05
> 5 casual partners at BL
2.80
< 0.01
STIs in 6 months pre-PrEP
2.22
<0.05
Increase in Nb casual partners
2.16
Neither overall condom use nor change in condom use were associated with STIs diagnosis in the 12 months following PrEP uptake
Golub S et al. CROI 2018 Boston 18

19. Testing for STIs in Last 12 months among MSM – an eCDC/Hornet Survey
Of those currently not on PrEP
Of those currently on PrEP
Men taking PrEP test more often for STIs
Noori T. et al EACS 2017

20. Increases in Extra-Genital Testing in the US (2013-2015)
% increase in Ct and GC NAAT volume at LabCorp,
Specimen type /pathogen
Male
rectal Ct/GC (n)
o/p GC (n)
Female
urogenital CT/GC.
ages (n)
urethral Ct/GC, (n)
2013 (Q2)
4,942
6,603
249,854
138,393
2015 (Q4)
12,973
18,458
384,047
209,243
Schillinger JA et al National STD Prevention Conference

21. Incidence of Gonorrhea and Chlamydia among MSM using PrEP
Over the next decade, 40% of NG and CT infections would be averted (40% PrEP coverage)
Jenness et al CID 2017

22. Summary
TASP/PrEP implementation: high rates of condomless sex and STIs did not undermine high efficacy against HIV transmission or acquisition
New interventions should be accompanied by measures to reinforce individual perception of STIs risk and behavioral changes including condom use
Frequent testing, early diagnosis and treatment and better partner notification should help reduce HIV and STIs incidence
PrEP cohorts are a unique opportunity to assess new strategies (behavioral and biomedical) to prevent STIs
STIs should not be an excuse to deny PrEP access
Community and individuals empowerment is key to counter the increase in STIs associated with biomedical interventions

23. Acknowledgments 23 23