1. Laboratory Enhancement Study: Using the detuned assay to determine HIV incidence in Ontario October 1999 – July 2000 Robert S. Remis, Carol Major, Carol Swantee Margaret Fearon, Evelyn Wallace, Elaine Whittingham Department of Public Health Sciences, University of Toronto HIV Laboratory, Laboratory Services, Ontario Ministry of Health and Long-Term Care Public Health Branch, Ontario Ministry of Health and Long-Term Care Ontario HIV Treatment Network 3rd Annual Research Day Toronto, Ontario, November 9-10, 2001

2. MOHLTC, Laboratories Branch, IMC – 2001 Acknowledgements At the HIV LaboratoryAt the HIV Laboratory Lisa Santangelo and Cindi Farina, data collectionLisa Santangelo and Cindi Farina, data collection Lynda Healey, detuned assayLynda Healey, detuned assay Elaine McFarlane, data entry screensElaine McFarlane, data entry screens Len Neglia, mailout of questionnairesLen Neglia, mailout of questionnaires Regional PHLs, mailout of questionnairesRegional PHLs, mailout of questionnaires Physicians who prescribe HIV testing, supplementary dataPhysicians who prescribe HIV testing, supplementary data Frank McGee, AIDS Bureau for base fundingFrank McGee, AIDS Bureau for base funding Ontario HIV Treatment Network for initial project fundingOntario HIV Treatment Network for initial project funding CIDPC, Health Canada for continued project fundingCIDPC, Health Canada for continued project funding

3. MOHLTC, Laboratories Branch, IMC – 2001 Introduction Serodiagnostic data may useful for surveillanceSerodiagnostic data may useful for surveillance However,However, persons who test may not be representativepersons who test may not be representative data quality inconsistentdata quality inconsistent True HIV incidence and HIV prevalence cannot be derived directly from dataTrue HIV incidence and HIV prevalence cannot be derived directly from data

4. MOHLTC, Laboratories Branch, IMC – 2001 Introduction Testing of HIV-positive specimens using less sensitive (“detuned”) assay permits the identification of persons who recently seroconverted (< 4 months)Testing of HIV-positive specimens using less sensitive (“detuned”) assay permits the identification of persons who recently seroconverted (< 4 months) Allows calculation of HIV incidence density, an important indicator usually difficult to measureAllows calculation of HIV incidence density, an important indicator usually difficult to measure

5. MOHLTC, Laboratories Branch, IMC – 2001 Study objectives To accurately determine the number of persons newly testing positive for HIVTo accurately determine the number of persons newly testing positive for HIV To determine the distribution of exposure category among newly diagnosed HIV-infected personsTo determine the distribution of exposure category among newly diagnosed HIV-infected persons To estimate HIV incidence density among persons undergoing HIV testingTo estimate HIV incidence density among persons undergoing HIV testing

6. MOHLTC, Laboratories Branch, IMC – 2001 Data collection and management Questionnaire sent with HIV-positive resultsQuestionnaire sent with HIV-positive results and 1:200 sample of HIV-negative resultsand 1:200 sample of HIV-negative results Data on risk factors for HIV infection and HIV test historyData on risk factors for HIV infection and HIV test history Questionnaire may be returnedQuestionnaire may be returned by mail or faxby mail or fax by telephone interviewby telephone interview Data entered in Microsoft AccessData entered in Microsoft Access

7. MOHLTC, Laboratories Branch, IMC – 2001 Laboratory methods Modified Abbott 3A11 EIA kit (Oct 1999-Oct 2000)Modified Abbott 3A11 EIA kit (Oct 1999-Oct 2000) Serum diluted to 1:20,000Serum diluted to 1:20,000 Incubation period reduced to 30 minutesIncubation period reduced to 30 minutes Cut-off value increasedCut-off value increased Organon-Teknika (Oct 2000-Jul 2001)Organon-Teknika (Oct 2000-Jul 2001) Similar principle to Abbott EIASimilar principle to Abbott EIA Allows use of variable cut-off value reflecting varying “window period”Allows use of variable cut-off value reflecting varying “window period”

8. MOHLTC, Laboratories Branch, IMC – 2001 Data analysis NumeratorNumerator Non-reactive (discordant specimens) without risk factors imputed to NIR specimens based on reclassification from LESNon-reactive (discordant specimens) without risk factors imputed to NIR specimens based on reclassification from LES Initially, imputed as proportion of those with risk factor informationInitially, imputed as proportion of those with risk factor information Denominators (testers) handled similarlyDenominators (testers) handled similarly Incidence density =Incidence density = NR * 100 Testers * (t / 365) NR * 100 Testers * (t / 365)

9. MOHLTC, Laboratories Branch, IMC – 2001 Incidence (per 100 py) by exposure category Ontario, Oct 1999 - Jul 2001 Exposure category Incidence per 100 p-y MSMMSM-IDUIDU2.341.820.44 HR hetero LR hetero 0.220.04

10. MOHLTC, Laboratories Branch, IMC – 2001 Incidence (per 100 py) amomg MSM, MSM-IDU and IDU by health region, Ontario, Oct 1999 – Jul 2001 MSMMSM-IDUIDU TorontoOttawaOther3.380.821.386.3218.10.240.511.360.24 Ontario2.341.820.44

11. MOHLTC, Laboratories Branch, IMC – 2001 Incidence (per 100 py) among LR and HR heterosexual by health region Ontario, Oct 1999 - Jul 2001 HR hetero LR hetero TorontoOttawaOther0.260.170.210.040.070.02 Ontario0.220.04

12. MOHLTC, Laboratories Branch, IMC – 2001 Incidence (per 100 py) among MSM by health region and study period, Ontario, Oct 1999 - Jul 2001

13. MOHLTC, Laboratories Branch, IMC – 2001 Incidence (per 100 py) among MSM-IDU by health region and study period, Ontario, Oct 1999 - Jul 2001

14. MOHLTC, Laboratories Branch, IMC – 2001 Incidence (per 100 py) among IDU by health region and study period, Ontario, Oct 1999 - Jul 2001

15. MOHLTC, Laboratories Branch, IMC – 2001 Incidence calculated for selected exposure categories using different "window" periods with the OT assay, Jan-Jul 2001

16. MOHLTC, Laboratories Branch, IMC – 2001 Summary of findings Exposure category distribution among those with risk factor data not representativeExposure category distribution among those with risk factor data not representative Trends in HIV incidenceTrends in HIV incidence MSM Toronto: Highest but decreasing;MSM Toronto: Highest but decreasing; MSM Ottawa: Initially low but increasing;MSM Ottawa: Initially low but increasing; MSM elsewhere: Intermediate and increasingMSM elsewhere: Intermediate and increasing IDU: high in Ottawa; lower elsewhereIDU: high in Ottawa; lower elsewhere

17. MOHLTC, Laboratories Branch, IMC – 2001 Interpretation Number of discordant samples and HIV tests by exposure category were modeledNumber of discordant samples and HIV tests by exposure category were modeled Interpretation of HIV incidence must incorporate knowledge of patterns in HIV test seeking behavioursInterpretation of HIV incidence must incorporate knowledge of patterns in HIV test seeking behaviours Observed HIV incidence likely higher than for populationObserved HIV incidence likely higher than for population

18. MOHLTC, Laboratories Branch, IMC – 2001 Conclusions HIV serodiagnostic program extremely useful for HIV surveillanceHIV serodiagnostic program extremely useful for HIV surveillance Detuned assay provides insights about a critical indicator of the HIV epidemic at low costDetuned assay provides insights about a critical indicator of the HIV epidemic at low cost

19. MOHLTC, Laboratories Branch, IMC – 2001 Conclusions Due to missing and unrepresentative data on risk factors and HIV test history, available data must be enhanced through supplementary means on an ongoing basisDue to missing and unrepresentative data on risk factors and HIV test history, available data must be enhanced through supplementary means on an ongoing basis Estimates of HIV incidence are almost certainly biased in upward directionEstimates of HIV incidence are almost certainly biased in upward direction Techniques to adjust or standardize will require detailed knowledge of HIV testing behavioursTechniques to adjust or standardize will require detailed knowledge of HIV testing behaviours