Ontario HIV Epidemiologic Monitoring Unit Department of Public Health Sciences and

1. Estimates of HIV incidence based on the detuned assay may be strongly biasedRobert S. Remis, Robert W.H. Palmer, Janet Raboud Ontario HIV Epidemiologic Monitoring UnitDepartment of Public Health Sciences and Division of Infectious Diseases, University of Toronto 14th International Conference on AIDS Barcelona, Spain, July 7-12, 2002 Abstract MoPeC3457

2. Background • Detuned assay an epidemiologist’s “philosopher’s stone”? • Transforms prevalence into incidence • Incidence = #S/LS / Tests * WP

3. Background • Incidence by detuned assay in prevalence studies may be biased; • Bias compounded when sera from diagnostic testing; • Three possible sources of bias: • persons who test not representative • HIV testing frequency may vary by HIV risk • persons who experience isolated high risk exposures or seroconversion illness more likely to test immediately following

4. Methods • Examined bias in incidence as a function of : 1) incidence density, 2) inter-test interval, 3) window period of detuned assay and 4) study duration • Parameter values: • incidence: literature review, cohort studies in Montreal and Vancouver, epidemiologic modelling of HIV among MSM in Ontario • inter-test interval: #tests MSM in Ontario • window period: OT Vironostika assay • study duration: likely scenarios • Output was bias as expressed by “observed” incidence density compared to “true” incidence density(ratio of Iest / Itrue)

5. Methods Determination incorporated: • Inter-test interval a function of incidence density: • five strata with scaled incidence density • inter-test interval varied inversely with incidence density • Seroconversion illness effect (SCE) • increased probability of HIV testing due to episodic high risk and symptoms of primary HIV infection • defined as additional proportion of newly infected persons testing <90 days following infection • values compared of initial outputs of model with proportion HIV tests from MSM discordant, 1999-2001

6. Methods – Parameter values used

7. No Ttest-Itrue, SCE = 0.0 No Ttest-Itrue, SCE = 0.2 No Ttest-Itrue, SCE = 0.4 Low Ttest-Itrue, SCE = 0.0 Low Ttest-Itrue, SCE = 0.2 Low Ttest-Itrue, SCE = 0.4 High Ttest-Itrue, SCE = 0.0 High Ttest-Itrue, SCE = 0.2 High Ttest-Itrue, SCE = 0.4 Bias (Iest /Itrue) as a function of Twin–Itrueinteraction and SCE varied through range of incidence

8. No Ttest-Itrue, SCE = 0.0 No Ttest-Itrue, SCE = 0.2 No Ttest-Itrue, SCE = 0.4 Low Ttest-Itrue, SCE = 0.0 Low Ttest-Itrue, SCE = 0.2 Low Ttest-Itrue, SCE = 0.4 High Ttest-Itrue, SCE = 0.0 High Ttest-Itrue, SCE = 0.2 High Ttest-Itrue, SCE = 0.4 Bias (Iest /Itrue) as a function of Twin–Itrueinteraction and SCE varied through range of inter-test interval

9. No Ttest-Itrue, SCE = 0.0 No Ttest-Itrue, SCE = 0.2 No Ttest-Itrue, SCE = 0.4 Low Ttest-Itrue, SCE = 0.0 Low Ttest-Itrue, SCE = 0.2 Low Ttest-Itrue, SCE = 0.4 High Ttest-Itrue, SCE = 0.0 High Ttest-Itrue, SCE = 0.2 High Ttest-Itrue, SCE = 0.4 Bias (Iest /Itrue) as a function of Twin–Itrueinteraction and SCE varied through range of window period

10. No Ttest-Itrue, SCE = 0.0 No Ttest-Itrue, SCE = 0.2 No Ttest-Itrue, SCE = 0.4 Low Ttest-Itrue, SCE = 0.0 Low Ttest-Itrue, SCE = 0.2 Low Ttest-Itrue, SCE = 0.4 High Ttest-Itrue, SCE = 0.0 High Ttest-Itrue, SCE = 0.2 High Ttest-Itrue, SCE = 0.4 Bias (Iest /Itrue) as a function of Twin–Itrueinteraction and SCE varied through range of study duration

11. Mean values of bias by SCE in presence of no, low and high interaction between inter-test interval and incidence density

12. Summary of observations • No bias in absence of SCE and Ttest-Itrueinteraction • SCE imore important source of bias than Ttest-Itrueinteraction • Biases as high as 7.3 under certain circumstances (high SCE and Ttest-Itrueinteraction) • Biases may still be considerable (e.g. 2-3) at plausible parameter values

13. Interpretation • Model used plausible values for MSM in Ontario • Good data not yet available for several parameters, especially Ttest-Itrueinteraction, inter-test interval and SCE • Biases may be different in other study populations; however, range of values probably spans most other situations • Did not investigate bias for different values of Tsce

14. Conclusions • Incidence density by detuned assay can be seriously overestimated; • Biases as high as 7-fold in some situations, considerable even at plausible values of parameters; • Bias mostly from SCE also if persons at increased HIV risk test more frequently; both likely to occur among MSM and possibly in other at-risk populations; • Incidence estimates using detuned assay must be interpreted with considerable caution; • Techniques to “standardise” incidence estimates from the detuned assay under development and could be extremely useful.

15. Acknowledgements • Instructional Media Centre, Laboratories Branch, Ontario Ministry of Health and Long-Term Care for preparation of the poster; • Frank McGee, coordinator, AIDS Bureau, Ontario Ministry of Health and Long-Term Care for core funding; • Carol Major, formerly of the Laboratories Branch, Ontario Ministry of Health and Long-Term Care for advice and collaboration.