1. The “rare patient” Julia del Amo ISCIII, Madrid, Spain

2. The Translational Power of Collaboration: Harnessing Large Datasets to Understand the HIV/AIDS Epidemic and to Optimize Care and Treatment Rare patients from cohort studies can inform public health policy

3. Definition of “rare” from the Oxford dictionary (of an event, situation, or condition) not occurring very often (of a thing) not found in large numbers and so of interest or value unusually good or remarkable

4. Synonyms and antonyms of rare Uncommon infrequent Scarce extraordinary – common – frequent – abundant – ordinary

5. To find uncommon events you need: To contextualize them to value their “uniqueness” To find the rare ones within large numbers of common events

6. What is the role of Extremely Large Datasets in HIV/AIDS and Global Cohort Collaborations regarding “rare patients” ?

7. International cohort collaborations allow identifying meaningful numbers of "rare subjects"

8. Those with uncommon and/or remarkable features Who are rare subjects in HIV/AIDS ? Rare “Exposures” and “Outcomes” Outcomes Exposures

9. Clinical presentations Response to treatment Socio-demographic characteristics Disease progression patterns Biological traits

10. Socio-demographic characteristics Women in Western epidemics Children in Western epidemics Migrants from specific origins Distinct ethnic minorities People over 70 years “Rare exposures”

11. Socio-demographic characteristics Women in Western epidemics Children in Western epidemics Migrants from specific origins Distinct ethnic minorities People over 70 years “Rare exposures” Depends on the setting

12. “Rare events”

13. Long-term non-progressors and elite controlers Rapid and very rapid disease progression Viraemic non progressor Seroconverters with narrow windows - primoinfected During pregnancy HIV-2

14. Long-term non-progressors and elite controlers Rapid and very rapid disease progression Viraemic non progressor Seroconverters with narrow windows - primoinfected During pregnancy HIV-2 Understanding Pathogenesis

15. Vertical transmission despite PMTCT Treatment in infants Presenters with < 50 cells/mm 3 ART response in non-B HIV-1 subtypes Uncommon adverse effects of ART Cause-specific mortality in specific groups Women Migrants Ethnic minorities

16. Vertical transmission despite PMTCT Treatment in infants Presenters with < 50 cells/mm 3 ART response in non-B HIV-1 subtypes Uncommon adverse effects of ART Cause-specific mortality in specific groups Women Migrants Ethnic minorities Policy Implications

17. Except for some groups such as migrants from Sub-Saharan Africa, the proportion of women in the HIV epidemic in Europe has been < 25% In Sub-Saharan African cohorts, women account for > 50% of the subjects What is rare in a setting may be common in another

19. Men Women Deaths 803 430 Deaths without AIDS 272 130

21. WE NAME SSA LA Asia Deaths 2195 13 26 25 10

22. Three axes- gender, ethnicity and social class – conform social health inequalities

23. Gender, ethnicity and social class should be viewed as EFFECT MODIFIERS rather than confounders requiring stratified analyses

24. Three axes- gender, ethnicity and social class – conform social health inequalities Gender, ethnicity and social class should be viewed as EFFECT MODIFIERS rather than confounders requiring stratified analyses  Incorrect assumption that unmeasured confounders are equally distributed within these three axes

25. Study key outcomes by geographical origin and sex in COHERE: Appropriateness of the timing of cART initiation and treatment interruptions cART Virological and immunological responses All-cause and cause-specific mortality

26. High numbers High power Low data quality Misclassification Non-differential

27. High numbers High power Low data quality Misclassification Non-differential

28. Strategic questions on rare subjects need to be formulated within large datasets

29. using standardized definitions to provide the adequate statistical power for its translation into public health policy quality control procedures Strategic questions on rare subjects need to be formulated within large datasets

30. Founding networks

31. Thank you for your attention