Affiliations: 1. Rwanda-Zambia HIV Research Group

1. HIV-1 positive Rwandan women have a high frequency of long-term survival: 20-year follow-up from a prospective cohort study Philip Peters1,2, Jareen Meinzen-Derr1, Kayitesi Kayitenkore1,3, Etienne Karita1,3, Erin Shutes1,3, D. Kim1,4,Amanda Tichacek1,4, Susan Allen1,4,5 Please visit us at www.rzhrg.org Affiliations: 1. Rwanda-Zambia HIV Research Group 2. Division of Infectious Diseases, Emory University, Atlanta, USA 3. Projet San Francisco, Kigali, Rwanda 4. Emory Rollins School of Public Health, Atlanta, USA 5. Emory AIDS International Training and Research Program R Z H R G A I T R P

2. Background / Goals of Study • Detailed data on the natural history of HIV in Africa remains inadequate • Important for evaluating the impact of interventions such as ARVs • Describe rates of long-term survival in HIV-infected Rwandan women R Z H R G A I T R P

3. Rwandan Cohort • 548 HIV infected women were recruited from prenatal clinics starting in 1986 • 401 (73%) HIV seroprevalent in 1986 • 147 (27%) initially HIV neg with known dates of seroconversion (between 1986 – 93) Location : Kigali, Rwanda • Capital city of 850,000 people • 100% infections caused by subtype A virus R Z H R G A I T R P

4. Rwandan Cohort • Study Design : Prospective Closed Cohort • Follow-up until February 2006 at 3-6 monthly intervals • Clinic closed in 1994 as result of genocide • > 5000 total person years of follow-up • > 90% retention • ARV therapy initiated in mid-2003 • Primary End-Point : Non-Genocide Mortality A I T R P R Z H R G

5. Select Demographic and Clinical Features R Z H R G A I T R P

6. Overall Outcomes: Oct 1986 – Feb 2006 R Z H R G A I T R P

7. Period Specific Mortality Rates *p < 0.01 R Z H R G A I T R P

8. R Z H R G A I T R P

9. Known Date R Z H R G A I T R P

10. Known Date R Z H R G A I T R P

11. Long-term Survivors – a subset of 96 women tested in 1998 * Prior to starting ARVs R Z H R G A I T R P p < 0.01

12. Possible Explanations for the High Proportion of Long-term Survivors • Gender • HIV-1 Sub-type A • Senegal1 • Uganda2 • Tanzania3 Ref: 1. Kanki, P.J., et al., JID 1999; 179: 68-73 2. Kaleebu, P., et al., JID 2002; 185: 1244-50 3. Vasan, A., et al., CID 2006; 42:843–52 R Z H R G A I T R P

13. Possible Explanations for the High Proportion of Long-term Survivors • Genetic Factors in Rwandan cohort4 • CCR5 32 present in 0%5 • HLA B*576 • present in 34% survivors*7 • present in 9% deceased • Immunologic Factors8 * p<0.01 Ref: 4. Heeney, J.L., et al., Science 2006; 313: 462-66 5. Tang, J., et al., Genes and Immunity 1999; 1: 20-7 6. Lazaryan, A., et al., J Virol 2006; 80: 6056-60 7. Tang and Lazaryan (personal comm) 8. Simon, V., et al., Lancet 2006; 368: 489-504 R Z H R G A I T R P

14. Conclusions • HIV infected Rwandan women had higher rates of long-term survival than predicted • Viral factors (subtype A virus) and host factors (HLA B*57) could contribute to this slower disease progression • Most long-term survivors still have evidence of disease progression R Z H R G A I T R P

15. Acknowledgements Thank you! The investigators would like to thank all of the women in Rwanda who participated and the staff at Projet San Francisco who made this study possible. Funding: NIAID R01 23980, R01 40951, R01 51231, NICHD R01 40125, NIMH R01 66767, FIC D43 TW001042, International AIDS Vaccine Initiative R Z H R G A I T R P

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