HIV and Other Conditions Carina Marquez MD University of California San Francisco Carina Marquez Mucunguzi Atukunda Joshua Nugent Edwin Charlebois Gabriel Chamie Florence Mwangwa ID: 1032893
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1. Impact of a community-wide HIV test and treat intervention on population-level tuberculosis transmission in rural UgandaHIV and Other ConditionsCarina Marquez MD, University of California San Francisco Carina Marquez, Mucunguzi Atukunda, Joshua Nugent, Edwin Charlebois, Gabriel Chamie, Florence Mwangwa, Emmanuel Ssemmondo, Joel Kironde, Jane Kabami, Asiphas Owaraganise, Elijah Kakande, Rahcel Abbott, Bob Ssekaynzi, James Ayieko, Theodore Ruel, Dalsone Kwariisima, Moses Kamya, Maya Petersen, Diane Havlir, Laura Balzer
2. NoneDisclosures
3. HIV and Tuberculosis (TB) are linked epidemicsThe benefit of treating HIV on reducing the risk of active TB disease is well-established on an individual and community-level. The SEARCH intervention, a universal HIV ‘test and treat’ strategy with patient-centered streamlined care, reduced the incidence of active TB disease among people with HIV by 59% (Havlir NEJM 2019). Few public health interventions demonstrate an effect on TB transmission on a population-levelBackground
4. To assess whether the SEARCH intervention, a universal ‘HIV test and treat’ strategy with streamlined patient-centered care, reduced TB transmission on a population level Objective
5. To assess whether the SEARCH intervention, a universal ‘HIV test and treat’ strategy with streamlined patient-centered care, reduced TB transmission on a population level Primary Outcome: 1-year cumulative incidence of TB infectionTB infection- reservoir drives TB disease and deathIncident TB Infection-marker recent TB acquisition and community-wide transmission. Objective
6. Design: Phase 1, 32-community cluster randomized trial in rural Kenya and Uganda(NCT01864603), 2013-2017. SEARCH Hypothesis: HIV “test and treat” with universal ART using a multi-disease, streamlined care approach will reduce new HIV infections and improve community health compared to a country guideline approach.SEARCH Intervention components:SEARCH Trial1. Petersen JAMA 2017; 2. Havlir NEJM 2019; 3. Jakubowski Lancet ID 2022; 4. Hickey PLOS Med 2021Multi-disease health campaigns : Testing for HIV, Malaria, Hypertension, Diabetes and more Intervention Communities:Baseline+ annual Multi-disease Health FairsStreamlined HIV/NCD care ART eligibility: All people with HIVControl Communities:Baseline Multi-disease Health Fair HIV/NCD care and ART eligibility per country guidelines HIV Outcomes• Cumulative 3-year HIV incidence• HIV RNA metricsCare cascade: Testing, ART start, virologic suppressionCommunity Health Outcomes TB, NCD Control, Mortality, Household Economics Key Findings: Community health:1-4: population-level HIV viral suppression2 HIV associated mortality and TB2 household economic and education outcomes3
7. Study Population and ProceduresNested TB Infection StudyHousehold visits in Eastern Uganda to place tuberculin skin testsNested cohort in SEARCH Phase 1 Trial9 Communities in Eastern UgandaSampling: Household, random sample enriched for households with people with HIV. 200 per community.Eligibility: all residents >5 years of age living in a household participating in a sub-study.Procedures: Tuberculin skin test (TST) placement at baseline (2015-2016) and one year later (2016-2017) in TST negative cohort. TB-specific questionnaire: TB contact, TB history, BCG vaccination (scar or vaccine record).Demographics and HIV status assessed during SEARCH study
8. Outcome: 1-year cumulative incidence TB infection Incident TB Infection defined as conversion from a negative TST at baseline to positive at 1 year follow-up. Positive TST= Induration >10mm or >5 mm for people with HIV Analytic Population: Children and adults over the age of 5 in 9 SEARCH communities in Eastern Uganda, 4 intervention / 5 control communitiesComparison between randomized arms with Targeted Maximum Likelihood Estimation (TMLE)1-2Accounting for sampling, measurement of TB status, and clusteringPre-specified subgroups: age categoriesOne-sided testing of null hypothesis: SEARCH did not reduce incidence MethodsStatistical Analysis 1. Balzer Biostatistics 2021; 2. Nugent arXiv, 2022
9. Results- Study Flow Diagram 4,884 (58%) administered TST at baseline9 communities1,435 households sampled8,420 individuals, 5+ years of age3,831 (78%) TST-negative cohort3,003 (78%) of at-risk individuals administered TST at follow-up year 122% TST positive at baseline
10. Demographics at Baseline Baseline InterventionControlN22432641Age 5-11 12-17 18-24 25-49 50 + 945 (42.1%)380 (16.9%)215 (9.6%)464 (20.7%)239 (10.7%) 1132 (42.9%)368 (13.9%)203 (7.7%)639 (24.2%)299 (11.3%)Gender Men Women 997 (44.4%)1246 (55.6%) 1213 (45.9%)1428 (54.1%)High-risk occupation*343 (15.3%)335 (12.7%)Lowest wealth quintile539 (24%)528 (20.0%)HIV225 (10%)342 (12.9%)Person with HIV in household1043 (46.5%)1214 (46%)High mobility137 (6.1%)49 (1.9%)Alcohol use (adults)208 (9.3%)191 (7.2%)TB contact in last year95 (4.2%)75 (2.8%)BCG vaccine2065 (92.1%)2467 (93.4%)* High-risk TB occupation- food/bar worker, transport, military/police; **Mobile: >6 months living outside of the parish
11. Demographics at Baseline Baseline InterventionControlN22432641Age 5-11 12-17 18-24 25-49 50 + 945 (42.1%)380 (16.9%)215 (9.6%)464 (20.7%)239 (10.7%) 1132 (42.9%)368 (13.9%)203 (7.7%)639 (24.2%)299 (11.3%)Gender Men Women 997 (44.4%)1246 (55.6%) 1213 (45.9%)1428 (54.1%)High-risk occupation*343 (15.3%)335 (12.7%)Lowest wealth quintile539 (24%)528 (20.0%)HIV225 (10%)342 (12.9%)Person with HIV in household1043 (46.5%)1214 (46%)High mobility137 (6.1%)49 (1.9%)Alcohol use (adults)208 (9.3%)191 (7.2%)TB contact in last year95 (4.2%)75 (2.8%)BCG vaccine2065 (92.1%)2467 (93.4%)* High-risk TB occupation- food/bar worker, transport, military/police; **Mobile: >6 months living outside of the parish
12. Primary Outcome: SEARCH intervention reduced TB Infection by 27% (aRR: 0.73; 95% CI: 0.58-0.93, p<0.01)1 Year Cumulative Incidence of TB Infection:Intervention: 16%Control: 22%Results- Effect of SEARCH Intervention on TB Infection Incidence
13. Results- Stratified by AgeOverallAge 5-11Age 12+Adjusted Risk Ratio (aRR)1.0Relative Risk of incident TB infection in intervention vs. control arm of SEARCH trial*, overall and stratified by age *-Incident TB Infection= tuberculin skin test conversion from negative at baseline to positive one year later-one-sided p-value to test hypothesis that the SEARCH intervention did not reduce TB
14. Potential MechanismsMultiple Areas for ImpactIntervention
15. No gold standard for measuring TB InfectionDifferential in participation adjusted for in our pre-specified statistical analytic planLimitations
16. A universal HIV Test and treat intervention reduced incident TB infection, a marker of population-level TB transmission. Investments in community-level HIV interventions have direct impacts both on HIV and broader population-level benefits, including reductions in TB infection.Conclusions
17. ACKNOWLEDGEMENTShttp://www.searchendaids.comThank you NIH and PEPFAR for supporting SEARCH We are grateful for all who work on SEARCH, our multilateral partners, and the communities we serve. Co-PIs Diane Havlir, Moses Kamya, Maya Petersen Economist: Harsha ThirumurthyStatistician: Laura Balzer, Mark Van der Laan Social Scientist: Carol CamlinVice-Chair: Edwin Charlebois Modeling: Britta Jewell, Anna BershteynVirologist: Teri Liegler Statistician TB Infection Substudy: Joshua NugentKEMRI: Elizabeth Bukusi, Norton Sang, James Ayieko, Kevin Kadeke UCSF: Tamara Clark, Gabe Chamie, Ted Ruel, Vivek Jain, Starley Shade, Doug Black, Cait Koss, Lillian Brown, Craig CohenIDRC-UCSF: Dalsone Kwarisiima, Jane Kabami, Dathan Mirembe, Asiphas Owaraginise, Mucu AtukundaTB Infection Study TeamTB infection Substudy:NIH/NIAD K23AI118592; R01AI15209, UCSF AIDS Research Institute Strategic Funding
18. Extra Slides
19. 1. Efficient Visits for Patients and Staff• ART start at first clinic visit as indicated• Triage by nurse or other extender Co-location of services• Clinic visits/ART dispensation every 3 months (rather than every 1-2 months)2. Patient-centered approach to careWelcoming environmentFostering trust, connection, and a sense of investment in the patientFlexible clinic hoursTiered TrackingMulti-disease chronic care model 3. Mobile phone hotline access for patients• Easy triage of medical questions• Appointment/scheduling logistics for retention4. Appointment reminders by mobile phone/SMS• One week to few days in advance• Retention tool5. Viral Load Counseling• Structured format for discussion of undetectable and detectable resultsKwarsiima, JIAS 2017Streamlined Care Interventions HIV/NCD* “Chronic Care Model”