HIV1 subtype differences in disease progression: observations from Uganda

1
HIV-1 subtype differences in disease progression
observations from Uganda

• Noah Kiwanuka, MD, PhD
• Rakai Health Sciences Program, Uganda
• Presented at The Fogarty International Center
  Satellite Meeting,
• Mexico City AIDS conference, 3rd August
  2008.

2
Natural history of HIV infection in an average
patient without ART from seroconversion to death

• Fauci AS, et al. Ann Intern Med 1996 124654-663

3
Rakai Uganda
4
HIV-1 subtype distribution in Uganda

• Central Uganda
• Subtype D 42 48
• Subtype A 49 57
• Southwestern Uganda
• Subtype D 55
• Subtype A 15 18
• Recombinants 22 30

5
Earlier studies
Study Subjects Viral Data Results
Kanki, 1999 54 incident V3
sequence More AIDS in non-A subtypes than
A Kaleebu, 2001 47 prevalent HMA
More CD4 decline 117
incident in D than A Kaleebu, 2002
1045 prevalent HMA and More death in D
V3 serology than A Senkaali, 2004
142 incident V3 specific More AIDS and
Serology death in D than
non-D (A, B C) Vasan, 2006 428
prevalent DNA More AIDS death sequencing
in D than A
6
Limitations of above studies

• Mainly prevalent cases of unknown duration
• of infection
• Small numbers of incident cases
• Subtype assays had a limited ability to identify
• inter-subtype recombinants

7
Recent Rakai study

• Conducted among incident cases from a
  population-based
• cohort
• Sample size of 349
• HIV-1 subtype data determined by MHA which can
• distinguish pure strains from recombinants and
  infection with
• multiple strains
• Kiwanuka et al. J Infect Dis,
  2008197(5)707-713

8
KM graph of Time to AIDS
D vs A p 0.017 R vs A p 0.017M vs A p 0.002
9
KM graph of Time to Death
D vs A p 0.009 R vs A p 0.002 M vs A p 0.02
10
Overall summary

• In Uganda,
• Infection with Subtype D, A/D recombinants, or
  multiple HIV strains is associated with faster
  progression to AIDS and to death relative to
  infection with subtype A