Acute HIV infection detection and control reduces HIV infectiousness and transmission risk behavior among men who have sex with men in Bangkok, Thailand

1. Acute HIV infection detection and control reduces
HIV infectiousness and transmission risk behavior
among men who have sex with men
in Bangkok, Thailand
Frits van Griensven, Nittaya Phanuphak, Eugène Kroon,
James Fletcher, Suteera Pinyakorn, Nitiya Chomchey,
Siriwat Akapirat, Rapee Trichavaroj, Mark de Souza,
Jerome Kim, and Jintanat Ananworanich,
on behalf of the RV254/SEARCH 010 Study Group

2. Background
 Antiretroviral treatment (ART) reduces HIV viral load and HIV
transmission in HIV discordant heterosexual couples1 and likely
MSM2
 Despite increased uptake of ART since 1996, HIV incidence in MSM
continues on a global level3
 In rising and ongoing HIV epidemics in MSM, such as in Bangkok,
most HIV transmission may occur prior to ART initiation4
 Newly HIV infected MSM in Bangkok are mostly young men in a
multi risk factor environment, which includes unidentified acute and
newly HIV infected other MSM5
 Phylogenetic clustering of new HIV infections in MSM supports
acute HIV infection as one of the main drivers of ongoing HIV
transmission in MSM in rising and ongoing HIV epidemics4,6,7
1Cohen et al. N Engl J Med 2011;365:493-505 (HPTN052); 2Porco et al. AIDS 2004;18:81-88; 3Beyrer
et al. Lancet 2012;380:367-77; 4 Fisher et al. AIDS 2010; 24(11):1739-47; 5van Griensven et al. AIDS
2013;27(5):825-32; 6Audelin et al. J Acquir Immune Defic Syndr 2013;62(1):102-8; 7Ye J, et al. PLoS
ONE 2013;8(1): e54238. doi:10.1371/journal.pone.0054238

3. RV254/SEARCH010 Study
A cohort of individuals in acute HIV infection (AHI) in Bangkok, Thailand
Purpose:
Describe clinical, immunological, and virological characteristics
during AHI for vaccine development and (functional) HIV cure
insights
Describe demographics and behavioral risk factors for those
identified with acute HIV infection
Intervention:
Immediate initiation of ART upon detection of AHI
Behavioral risk reduction counseling
Outcomes:
Markers of HIV disease progression or cure
Behavioral change

4. Screening EIA/NAT
69,911 samples
136 AHI identified
April 2009-March 2013
90 MSM in AHI identified
90% undetectable integrated
HIV-DNA in PBMC at 1 year
Candidates for functional cure
research
screening
3 days
36 not included in study
10 non-MSM
To be
reported
elsewhere
Here we look at reduction in
HIV VL and transmission
risk behavior to assess
possible impact of AHI
control on epidemic spread
88 MSM started ART
2 days after study entry
RV254/SEARCH010 Study

5. Baseline Characteristics (n=88) Values
Mean (SD) age 28.5 (7.0) years
Mean (SD) duration of infection 16.5 (6.6) days
4th Gen staging
Stage 1 (NAT+, 4th gen-, 3rd gen-)
Stage 2 (NAT+, 4th gen+, 3rd gen-)
Stage 3 (NAT+, 4th gen+, 3rd gen+, WB- or WB ind)
19 (21.6%)
21 (23.9%)
48 (54.6%)
Mean CD4 (SD), cells/mm3 412 (189)
Mean HIV RNA (SD), log10 copies/ml
Plasma (n=88)
Seminal plasma (n=47)
Anal lavage (n=58)
5.62 (1.00)
4.02 (1.30)
2.58 (0.76)
HIV-1 subtype CRF_01AE 73%

6. Baseline Behavioral Characteristics (n=86) Values
Mean (SD) age at first sexual intercourse (years) 18.5 (2.5)
Sexual Partners in last 4 months
None
1
2-4
> 5
Decline to answer
0%
12%
55%
30%
5%
Any unprotected sexual intercourse in 4 months
prior to study entry 83.7%
With: Regular Partner
Casual Partner
Commercial Sex Worker
Person who gives money/goods
IDU partner
64%
57%
7%
7%
11%

7. Blood plasma viral load

8. Beyond week 2:
If blood plasma VL < detection, also seminal plasma VL < detection
Seminal plasma viral load

9. Anal lavage viral load

10. Sexual Partners
in last 4 months
Baseline
(n=86)
Week 24
(n=68)
Week 48
(n=62)
None
1
2-4
> 5
Decline to answer
0%
12%
55%
30%
5%
18%
34%
32%
7%
9%
11%
34%
34%
13%
8%
All wk 24 and wk 48 changes from baseline p<0.05
Changes from wk 24 to wk 48 NS
Reported number of sexual partners

11. wk 24 and wk 48 vs wk 0 p< 0.0001
wk 48 vs wk 24 NS
Unprotected intercourse over preceding 4 months

12. What is next?
Estimating the number of transmissions averted
through ART and behavioral change in AHI
David Wilson and colleagues
Kirby Institute
University of New South Wales

14. Discussion
 Initiation of ART during AHI may be a promising
intervention towards establishing functional HIV cure
 Sharp and rapid decreases in HIV blood plasma VL
and seminal plasma VL are seen, which translate into
potent HIV transmission reduction
 Impressive behavioral changes during the early
stages after AHI diagnosis, ART initiation and risk
reduction counseling
 Impact of early ART during AHI on transmission likely
depends on the HIV epidemic stage; literature puts
HIV transmissions resulting from AHI partners
anywhere from 4% to 50%1,2
1Goodreau et al. PLoS ONE 2012;7(11): e50522; 2Brenner et al. J Infect Dis 2007;195:951-9

15. Discussion (cont.)
 Seminal VL peaks at 30 days post infection in
untreated subjects3 while in this cohort immediate
decline was seen on ART and 73% VL < detection at
week 4
 Near 100% undetectable VL in seminal plasma at
weeks 12 and 24 plus 100% correlation with blood
plasma VL
This contrasts with seminal plasma VL studies in
North American MSM with undetectable blood plasma
VL on ART4,5
3Pilcher et al. AIDS 2007;21:1723-30
4Politch et al. AIDS 2012;26:1535-43
5Sheth et al. AIDS 2009;23:2050-4

16. Conclusion
 Early ART greatly reduces infectiousness in AHI
 Impressive changes in risk behavior after ART and
risk reduction counseling initiation, sustained up to
48 weeks
 AHI detection and control may be a powerful HIV
prevention measure in rising and ongoing HIV
epidemics in MSM

17. Acknowledgements
the RV254/SEARCH010 study volunteers
Funding from US Military HIV Research Program
AFRIMS
o Alexandra Schuetz
o Vatcharain Assawadarachai
o Yuwadee Phuangngern
o Wiriya Rutvisuttinunt
o Nantana Tantibul
o Panadda Sawangsinth
o Bessara Nuntapinit
o Wanwarang Khobchit
o Sakuna Suksawad
o Ajchariyarat Sangdara
o Kultida Poltavee
o Hathairat Savadsuk
o Suwittra Chaemchuen
o Robert Paris
o Surat Jongrakthaitae
o Chayada Sajiaweerawan
o Nipattra Tragonlugsana
o Putida Saetun
UCSF
o Victor Valcour
Yale
o Serena Spudich
o Idil Kore
Kirby
o David Wilson
o Lei Zhang
o Andrew Shattock
Thai Red Cross/Chula
o Praphan Phanuphak
o Thep Chalermchai
o Nipat Teeratakulpisarn
o Rungsun Rerknimitr
o Wiriyaporn Ridtitid
o Sukalya Lerdlum
o Duanghathai Suttichom
o Somprartthana Rattanamanee
o Peeraya Mangu
o Sasiwimol Ubolyam
o Mantana Pothisri
NIAID
o Irini Sereti
o Daniel Douek
o Netanya Sandler
o Mary Marovich
NCI
o Jacob Estes
o Robin Dewar
o Adam Rupert
SAIC-Frederick
o Frank Maldarelli
o Mary Kearney
o Ann Wiggins
Huntington Memorial
o Napaporn Sailasuta
VGTI
o Elias Haddad
o Lydie Trautmann
WRAIR
o Bonnie Slike
o Sodsai Tovanabutra
o Gustavo Kijak
Industry
o Thai GPO (TDF, 3TC, EFV, LPV/r)
o Gilead (TDF, FTC)
o Merck (EEV, RAL)
o Pfizer (MVC)
o Monogram (Trofile)