ART in acute and early HIV Infection

1
ART in acute and early HIV Infection

• Treatment for prevention

2
Two key factors determine infectiousnessviral
load and stage of infection
3

• Why is PHI so infectious?
• To what extent does PHI contribute towards HIV
  transmission at a population level?
• What is the best strategy to identify PHI?
• What is the evidence that ART is safe and confers
  any benefit at the individual level in this
  setting?

4
Why is PHI so infectious?
High rates STI/GUM (Pao AIDS 2005) Unknown HIV
status Viral characteristics (Keele PNAS 2008,
CHAVI) High rates of partner change (MacKellar
AIDS 2007)
108
107
106
105

104
eclipse
103
102
Virus Concentration in Extracellular Fluid or
Plasma (Copies/ml)
101
0
Virus dissemination
10-1
10-2
10-3
10-4
10-5
45
50
55
60
65
70
Time Post Exposure
Transmission
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To what extent does PHI contribute to HIV
transmission at a population level?
6
Individuals with PHI are 8x more likely to
transmit HIV to their sexual partners
Wawer et al Rates of HIV transmission per coital
act by stage of HIV infection in Rakai Uganda J
Infect Dis. 2005 May 1191(9)1403-9
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Stage of infection
Random mixing (high risk subpopulation)
Hollingsworth, Anderson Fraser, J Infect Dis
2008 AbuRaddad et al AIDS 2008, Pinkerton AIDS
Behavior 2008
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What is the best testing strategy to identify PHI?
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Methods of detecting Primary HIV Infection
(PHI) Pre-seroconversion detects virus antigen
0-20 days RNA or p24 Per-seroconversion
detects antibody 20-45 days Post seroconversion
antibody no antigen (bound up in immune
complexes) gt day 26
Pre- seroconversion
Per-seroconversion
Post seroconversion
8-17 days
12-26 days
12-26 days
20-45 days
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Could there be an individual benefit of early ART?
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12 weeks ART in early HIV infection delayed the
rate of CD4 decline
SMH n 89 received 12 weeks of ART in early
infection CASCADE n 179 not treated
Rate CD4 decline SMH 51 cells/year CASCADE 77
cells/year P 0.011

• Fidler S, et al AIDS. 2007 Jun 1921(10)1283-91.
• (Rosenberg 2000, Kaufman 2004, Al-Harthi 2007,
  Lampe et al 2007, Hecht et al 2006 Streeck
• ACTGA57217 )

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Kinloch
Hoen
Hecht
Streeck
Fidler
Lampe
Goujard
Fidler, Fox, Porter, Weber Current Opinion in
Infectious diseases 21 1 4-10 2008
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Onward HIV transmission risk remains after
stopping ART in PHI
N 441 treated PHI SPARTAC UK register of
seroconverters
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If we treat PHI with intermittent ARTIs it safe
to stop?

• Drug induced resistance Spartac 2
• Cardiovascular disease risk , Is there an
  increased risk of CVD like SMART?

(Spartac TSC Open report 2009)
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Summary

• Targeted interventions with improved diagnosis of
  hyper-infectious cases makes sense.
• ART in PHI combined with
• short term behavioural modification,
• STI treatment
• Male circumcision
• could have a highly significant impact on the
  epidemic at a population level.
• Feasibility studies addressing this concept are
  planned (MP3 Malawi and PopART, TasP, Test n
  treat)

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Thanks

• SPARTAC participants and collaborators
• UK register of seroconverters participants and
  collaborators
• CASADE collaboration participants and
  collaborators
• Primary HIV infection study Participants and
  collaborators
• Imperial College London Jonathan Weber,
  Christophe Fraser, Becky Baggaley, Geoff Garnett,
  Emma Thomson, Julie Fox, Liz Hamlyn
• MRC CTU Abdel Babiker, Kholoud Porter, Fiona
  Ewings
• University of Oxford Rodney Phillips, John Frater
• CHAVI Mike Cohen, Bart Haynes, Andrew McMichael
• PopART Collaboration Richard Hayes, David Ross,
  Ade Fakoya, Debby Watson-Jones, Helen Ayles,
  Peter Godfrey-Faucett, Liz Corbett, Heiner
  Grosskurt, Anatoli Kamali