Kathleen E Wirth1, Tendani Gaolathe2, Molly Pretorius Holme3, Mompati Mmalane2, Etienne Kadima2, Unoda Chakalisa2, Kutlo Manyake2, Atang Matildah Mbikiwa2, Selebaleng V Simon2, Rona Letlhogile2, Kutlwano Mukokomani2, Erik van Widenfelt2, Sikhulile Moyo4, Kara Bennett5, Jean Leidner6, Kathleen M Powis7, Refeletswe Lebelonyane8, Mary Grace Alwano9, Joseph Jarvis10, Scott L Dryden-Peterson11, Coulson Kgathi2, Janet Moore12, Pam Bachanas12, Elliot Raizes12, William Abrams9, Lisa Block13, Baraedi Sento14, Vlad Novitsky3, Shenaaz El-Halabi8, Tafireyi Marukutira9, Lisa A Mills9, Connie Sexton12, Sherri Pals12, Roger L Shapiro3, Rui Wang15, Quanhong Lei16, Victor DeGruttola16, Joseph Makhema4, Myron Essex4, Shahin Lockman11, Eric J Tchetgen Tchetgen17. 1. Department of Biostatistics, Harvard T H Chan School of Public Health, Boston, MA, USA. Electronic address: kathleen.wirth@gmail.com. 2. Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana. 3. Department of Immunology and Infectious Diseases, Harvard T H Chan School of Public Health, Boston, MA, USA. 4. Department of Immunology and Infectious Diseases, Harvard T H Chan School of Public Health, Boston, MA, USA; Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana. 5. Bennett Statistical Consulting, Ballston Lake, NY, USA. 6. Goodtables Data Consulting, Norman, Oklahoma, USA. 7. Department of Immunology and Infectious Diseases, Harvard T H Chan School of Public Health, Boston, MA, USA; Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana; Department of Medicine, Massachusetts General Hospital, Boston, MA, USA; Department of Pediatrics, Massachusetts General Hospital, Boston, MA, USA. 8. Ministry of Health and Wellness, Botswana, Gaborone, Botswana. 9. Centers for Disease Control and Prevention-Botswana, Gaborone, Botswana. 10. Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana; Centers for Disease Control and Prevention-Botswana, Gaborone, Botswana. 11. Department of Immunology and Infectious Diseases, Harvard T H Chan School of Public Health, Boston, MA, USA; Botswana Harvard AIDS Institute Partnership, Gaborone, Botswana; Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. 12. Centers for Disease Control and Prevention, Atlanta, GA, USA. 13. Centers for Disease Control and Prevention, Atlanta, GA, USA; Intellectual Concepts, Atlanta, GA, USA. 14. Tebelopele Voluntary Counseling and Testing Center, Gaborone, Botswana. 15. Department of Biostatistics, Harvard T H Chan School of Public Health, Boston, MA, USA; Harvard Pilgrim Health Care Institute, Boston, MA, USA. 16. Department of Biostatistics, Harvard T H Chan School of Public Health, Boston, MA, USA. 17. Department of Biostatistics, Harvard T H Chan School of Public Health, Boston, MA, USA; Department of Statistics, The Wharton School at the University of Pennsylvania, Philadelphia, PA, USA.
Abstract
BACKGROUND: In settings with high HIV prevalence and treatment coverage, such as Botswana, it is unknown whether uptake of HIV prevention and treatment interventions can be increased further. We sought to determine whether a community-based intervention to identify and rapidly treat people living with HIV, and support male circumcision could increase population levels of HIV diagnosis, treatment, viral suppression, and male circumcision in Botswana. METHODS: The Ya Tsie Botswana Combination Prevention Project study was a pair-matched cluster-randomised trial done in 30 communities across Botswana done from Oct 30, 2013, to June 30, 2018. 15 communities were randomly assigned to receive HIV prevention and treatment interventions, including enhanced HIV testing, earlier antiretroviral therapy (ART), and strengthened male circumcision services, and 15 received standard of care. The first primary endpoint of HIV incidence has already been reported. In this Article, we report findings for the second primary endpoint of population uptake of HIV prevention services, as measured by proportion of people known to be HIV-positive or tested HIV-negative in the preceding 12 months; proportion of people living with HIV diagnosed and on ART; proportion of people living with HIV on ART with viral suppression; and proportion of HIV-negative men circumcised. A longitudinal cohort of residents aged 16-64 years from a random, approximately 20% sample of households across the 15 communities was enrolled to assess baseline uptake of study outcomes; we also administered an end-of-study survey to all residents not previously enrolled in the longitudinal cohort to provide study end coverage estimates. Differences in intervention uptake over time by randomisation group were tested via paired Student's t test. The study has been completed and is registered with ClinicalTrials.gov (NCT01965470). FINDINGS: In the six communities participating in the end-of-study survey, 2625 residents (n=1304 from standard-of-care communities, n=1321 from intervention communities) were enrolled into the 20% longitudinal cohort at baseline from Oct 30, 2013, to Nov 24, 2015. In the same communities, 10 791 (86%) of 12 489 eligible enumerated residents not previously enrolled in the longitudinal cohort participated in the end-of-study survey from March 30, 2017, to Feb 25, 2018 (5896 in intervention and 4895 in standard-of-care communities). At study end, in intervention communities, 1228 people living with HIV (91% of 1353) were on ART; 1166 people living with HIV (88% of 1321 with available viral load) were virally suppressed, and 673 HIV-negative men (40% of 1673) were circumcised in intervention communities. After accounting for baseline differences, at study end the proportion of people living with HIV who were diagnosed was significantly higher in intervention communities (absolute increase of 9% to 93%) compared with standard-of-care communities (absolute increase of 2% to 88%; prevalence ratio [PR] 1·08 [95% CI 1·02-1·14], p=0·032). Population levels of ART, viral suppression, and male circumcision increased from baseline in both groups, with greater increases in intervention communities (ART PR 1·12 [95% CI 1·07-1·17], p=0·018; viral suppression 1·13 [1·09-1·17], p=0·017; male circumcision 1·26 [1·17-1·35], p=0·029). INTERPRETATION: It is possible to achieve very high population levels of HIV testing and treatment in a high-prevalence setting. Maintaining these coverage levels over the next decade could substantially reduce HIV transmission and potentially eliminate the epidemic in these areas. FUNDING: US President's Emergency Plan for AIDS Relief through the Centers for Disease Control and Prevention.
BACKGROUND: In settings with high HIV prevalence and treatment coverage, such as Botswana, it is unknown whether uptake of HIV prevention and treatment interventions can be increased further. We sought to determine whether a community-based intervention to identify and rapidly treat people living with HIV, and support male circumcision could increase population levels of HIV diagnosis, treatment, viral suppression, and male circumcision in Botswana. METHODS: The Ya Tsie Botswana Combination Prevention Project study was a pair-matched cluster-randomised trial done in 30 communities across Botswana done from Oct 30, 2013, to June 30, 2018. 15 communities were randomly assigned to receive HIV prevention and treatment interventions, including enhanced HIV testing, earlier antiretroviral therapy (ART), and strengthened male circumcision services, and 15 received standard of care. The first primary endpoint of HIV incidence has already been reported. In this Article, we report findings for the second primary endpoint of population uptake of HIV prevention services, as measured by proportion of people known to be HIV-positive or tested HIV-negative in the preceding 12 months; proportion of people living with HIV diagnosed and on ART; proportion of people living with HIV on ART with viral suppression; and proportion of HIV-negative men circumcised. A longitudinal cohort of residents aged 16-64 years from a random, approximately 20% sample of households across the 15 communities was enrolled to assess baseline uptake of study outcomes; we also administered an end-of-study survey to all residents not previously enrolled in the longitudinal cohort to provide study end coverage estimates. Differences in intervention uptake over time by randomisation group were tested via paired Student's t test. The study has been completed and is registered with ClinicalTrials.gov (NCT01965470). FINDINGS: In the six communities participating in the end-of-study survey, 2625 residents (n=1304 from standard-of-care communities, n=1321 from intervention communities) were enrolled into the 20% longitudinal cohort at baseline from Oct 30, 2013, to Nov 24, 2015. In the same communities, 10 791 (86%) of 12 489 eligible enumerated residents not previously enrolled in the longitudinal cohort participated in the end-of-study survey from March 30, 2017, to Feb 25, 2018 (5896 in intervention and 4895 in standard-of-care communities). At study end, in intervention communities, 1228 people living with HIV (91% of 1353) were on ART; 1166 people living with HIV (88% of 1321 with available viral load) were virally suppressed, and 673 HIV-negative men (40% of 1673) were circumcised in intervention communities. After accounting for baseline differences, at study end the proportion of people living with HIV who were diagnosed was significantly higher in intervention communities (absolute increase of 9% to 93%) compared with standard-of-care communities (absolute increase of 2% to 88%; prevalence ratio [PR] 1·08 [95% CI 1·02-1·14], p=0·032). Population levels of ART, viral suppression, and male circumcision increased from baseline in both groups, with greater increases in intervention communities (ART PR 1·12 [95% CI 1·07-1·17], p=0·018; viral suppression 1·13 [1·09-1·17], p=0·017; male circumcision 1·26 [1·17-1·35], p=0·029). INTERPRETATION: It is possible to achieve very high population levels of HIV testing and treatment in a high-prevalence setting. Maintaining these coverage levels over the next decade could substantially reduce HIV transmission and potentially eliminate the epidemic in these areas. FUNDING: US President's Emergency Plan for AIDS Relief through the Centers for Disease Control and Prevention.
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