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HIV-1 subtype distribution

HIV-1 subtype C is not associated with higher risk of heterosexual transmission: a multinational study among African HIV-1 serodiscordant couples.

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HIV-1 subtype distribution

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  1. HIV-1 subtype C is not associated with higher risk of heterosexual transmission: a multinational study among African HIV-1 serodiscordant couples Erin Kahle1, Mary Campbell1, Jairam Lingappa1, Deborah Donnell2, Connie Celum1, Saidi Kapiga3, Raphael Ondondo4, Nelly Mugo1,5, Andrew Mujugira1, Kenneth Fife6, James Mullins1, Jared Baeten1 for the Partners in Prevention HSV/HIV Transmission Study Team 1University of Washington, Seattle, WA, USA; 2Fred Hutchinson Cancer Research Center, Seattle,WA, USA; 3London School of Hygiene and Tropical Medicine, London, United Kingdom; 4Kenya Medical Research Institute, Kisumu, Kenya; 5Kenyatta National Hospital, Nairobi, Kenya; 6Indiana University, Bloomington, IN, USA

  2. HIV-1 subtype distribution • HIV-1 is characterized by wide genetic diversity • Subtype is distributed geographically and by mode of transmission • Specific subtypes, such as C, have more dramatically spread through populations McCutchan FE, Jackson HM, IAVI Report, 2003.

  3. HIV-1 subtype C Estimated prevalence of HIV-1 http://www.bioafrica.net/subtype/subC/Map2_subtype_C_timeline.html

  4. HIV-1 subtype C Estimated prevalence of HIV-1 Estimated prevalence of HIV-1 subtype C

  5. HIV-1 subtype C Estimated prevalence of HIV-1 Estimated prevalence of HIV-1 subtype C Subtype C accounts for over 50% of HIV-1 infections worldwide

  6. Hypothesized reasons for differential geographic spread of subtype • Founder effect • Transmission advantage • Slower disease progression may allow more time for transmission • Behavioral/cultural differences in transmitting populations

  7. Limitations of subtype and transmission studies • Requires both infected and susceptible hosts (e.g. couples, MTCT) • Lack of subtype diversity within a single geographic region

  8. Objective Determine whether HIV-1 subtype C is associated with increased HIV-1 transmission among HIV-1 serodiscordant couples in eastern and southern Africa

  9. Study population

  10. Kenya Nairobi Eldoret Kisumu Thika Zambia Kitwe Ndola Lusaka Botswana Gabarone Tanzania Moshi S. Africa Cape Town Orange Farm Soweto Study sites Rwanda Kigali Uganda Kampala

  11. Study design Nested case-control, 1:4 ratio

  12. Study design Nested case-control, 1:4 ratio 123 Cases Genetically-linked transmitting couples

  13. Study design Nested case-control, 1:4 ratio 123 Cases Genetically-linked transmitting couples 502 Controls Non-transmitting couples selected proportional by gender and site to the entire cohort

  14. Subtype and sequencing Viral sequencing using blood plasma was performed on partial HIV-1 env (C2-V3-C3) and gag (p17-p24) genes and subtypes were determined using the REGA subtyping tool version 2.0

  15. Statistical methods • Adjusted logistic regression comparing HIV-1 transmission in subtype C versus non-C, controlling for age and gender • Additional factors were considered for confounding, including unprotected sex, sex acts, circumcision status, marriage/cohabitation, number of children • Study power: 80% power to detect a 1.4-fold increased odds of HIV-1 transmission for subtype C versus non-C at the alpha 0.05 level

  16. Population characteristics

  17. Population characteristics

  18. Population characteristics

  19. Population characteristics

  20. Population characteristics

  21. HIV-1 subtype regional distribution

  22. HIV-1 subtype and transmission

  23. HIV-1 subtype and transmission

  24. HIV transmission comparing subtype C and non-C Adjusted for age and gender

  25. HIV transmission comparing subtype C and non-C Adjusted for age and gender

  26. HIV transmission comparing subtype C and non-C Adjusted for age and gender No association detected between subtype C and HIV-1 transmission when compared separately against subtypes A and D

  27. Summary • First study to assess subtype C versus non-C and risk of sexual HIV-1 transmission • Geographically diverse population where viral linkage was available • HIV-1 subtype C was not associated with increased HIV-1 transmission when compared to non-C subtypes • Including when adjusted for plasma viral load

  28. Limitations • Primarily chronic infections in study cohort • May be unmeasured differences in study site or region that confound the results

  29. Conclusions • In a geographically diverse population of stable heterosexual African HIV-1 serodiscordant couples, subtype C is not associated with greater risk of HIV-1 transmission • Our data do not support the hypothesis that greater transmissibility of subtype C explains the explosive HIV-1 epidemic in southern Africa

  30. Acknowledgements University of Washington Coordinating Center and Central Laboratories, Seattle, USA: Connie Celum (principal investigator), Anna Wald (protocol co-chair), JairamLingappa (medical director), Jared M. Baeten, Mary Campbell, Lawrence Corey, Robert W. Coombs, James P. Hughes, AmaliaMagaret, M. Juliana McElrath, Rhoda Morrow, James I. Mullins Study sites and site principal investigators: Cape Town, South Africa (University of Cape Town): David Coetzee; Eldoret, Kenya (Moi University, Indiana University): Kenneth Fife, Edwin Were; Gaborone, Botswana (Botswana Harvard Partnership): Max Essex, Joseph Makhema; Kampala, Uganda (Infectious Disease Institute, Makerere University): EllyKatabira, Allan Ronald; Kigali, Rwanda (Rwanda Zambia HIV Research Group, and Emory University): Susan Allen, KayitesiKayitenkore, Etienne Karita; Kisumu, Kenya (Kenya Medical Research Institute, University of California San Francisco): Elizabeth Bukusi, Craig Cohen; Kitwe, Zambia (Rwanda Zambia HIV Research Group, and Emory University): Susan Allen, William Kanweka; Lusaka, Zambia (Rwanda Zambia HIV Research Group, and Emory University): Susan Allen, BellingtonVwalika; Moshi, Tanzania (Kilimanjaro Christian Medical College, Harvard University): SaidiKapiga, Rachel Manongi; Nairobi, Kenya (University of Nairobi, University of Washington): Carey Farquhar, Grace John-Stewart, James Kiarie; Ndola, Zambia (Rwanda Zambia HIV Research Group, and Emory University): Susan Allen, MubianaInambao; Orange Farm, South Africa (Reproductive Health Research Unit, University of the Witwatersrand): Sinead Delany-Moretlwe, Helen Rees; Soweto, South Africa (Perinatal HIV Research Unit, University of the Witwatersrand): Guy de Bruyn, Glenda Gray, James McIntyre; Thika, Kenya (University of Nairobi, University of Washington): Nelly RwambaMugo Data management was provided by DF/Net Research, Inc. (Seattle, USA) and site laboratory oversight was provided by Contract Lab Services (University of the Witwatersrand, Johannesburg, South Africa). • Mullins Lab, University of Washington • Study participants • Funding: Bill and Melinda Gates Foundation (26469) and the National Institutes of Health (P30 A127757 to UW CFAR, P01 057005, K08 AI074424) • Partners in Prevention HSV/HIV Transmission Study Team

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