Quantifying HIV transmission flow between high-prevalence hotspots and surrounding communities: a population-based study in Rakai, Uganda
Oliver Ratmann
(1)
,
Joseph Kagaayi
(2)
,
Matthew Hall
(3)
,
Tanya Golubchick
(3)
,
Godfrey Kigozi
(2)
,
Xiaoyue Xi
(1)
,
Chris Wymant
(3)
,
Gertrude Nakigozi
(2)
,
Lucie Abeler-Dörner
(3)
,
David Bonsall
(3)
,
Astrid Gall
(4, 5)
,
Anne Hoppe
(6)
,
Paul Kellam
(7)
,
Jeremiah Bazaale
(2)
,
Sarah Kalibbala
(2)
,
Oliver Laeyendecker
(8, 9)
,
Justin Lessler
(10)
,
Fred Nalugoda
(2)
,
Larry W Chang
(8, 2, 10)
,
Tulio de Oliveira
(11)
,
Deenan Pillay
(6)
,
Thomas C Quinn
(8, 9)
,
Steven J Reynolds
(2, 8, 9)
,
Simon E F Spencer
(12)
,
Robert Ssekubugu
(2)
,
David Serwadda
(2, 13)
,
Maria J Wawer
(2, 10)
,
Ronald H Gray
(2, 10)
,
Christophe Fraser
(3)
,
M Kate Grabowski
(2, 8, 11)
,
Helen Ayles
(14)
,
Rory Bowden
(15)
,
Vincent Calvez
(16, 17)
,
Myron Cohen
(18)
,
Anne Dennis
(18)
,
Max Essex
(19)
,
Sarah Fidler
,
Dan Frampton
,
Richard Hayes
,
Josh Herbeck
,
Pontiano Kaleebu
,
Cissy Kityo
,
Jairam Lingappa
,
Vladimir Novitsky
,
Nick Paton
,
Andrew Rambaut
,
Janet Seeley
,
Deogratius Ssemwanga
,
Frank Tanser
,
Tom Lutalo
,
Ronald Galiwango
,
Fred Makumbi
,
Nelson Sewankambo
,
Dorean Nabukalu
,
Anthony Ndyanabo
,
Joseph Ssekasanvu
,
Hadijja Nakawooya
,
Jessica Nakukumba
,
Grace Kigozi
,
Betty Nantume
,
Nampijja Resty
,
Jedidah Kambasu
,
Margaret Nalugemwa
,
Regina Nakabuye
,
Lawrence Ssebanobe
,
Justine Nankinga
,
Adrian Kayiira
,
Gorreth Nanfuka
,
Ruth Ahimbisibwe
,
Stephen Tomusange
,
Ronald Galiwango
,
Margaret Nakalanzi
,
Joseph Otobi
,
Denis Ankunda
,
Joseph Ssembatya
,
John Ssemanda
,
Emmanuel Kato
,
Robert Kairania
,
Alice Kisakye
,
James Batte
,
James Ludigo
,
Abisagi Nampijja
,
Steven Watya
,
Kighoma Nehemia
,
Sr. Margaret Anyokot
,
Joshua Mwinike
,
George Kibumba
,
Paschal Ssebowa
,
George Mondo
,
Francis Wasswa
,
Agnes Nantongo
,
Rebecca Kakembo
,
Josephine Galiwango
,
Geoffrey Ssemango
,
Andrew Redd
,
John Santelli
,
Caitlin Kennedy
,
Jennifer Wagman
,
Aaron Tobian
1
Department of Mathematics [Imperial College London]
2 Rakai Health Sciences Program
3 Big Data Institute - Nuffield Department of Medicine [Oxford, UK]
4 European Molecular Biology Laboratory [Hinxton]
5 EMBL-EBI - European Bioinformatics Institute [Hinxton]
6 UCL - University College of London [London]
7 Imperial College London
8 Johns Hopkins University School of Medicine [Baltimore]
9 NIAID-NIH - National Institute of Allergy and Infectious Diseases [Bethesda]
10 Johns Hopkins Bloomberg School of Public Health [Baltimore]
11 UKZN - University of KwaZulu-Natal [Durban, Afrique du Sud]
12 Department of Statistics [Warwick]
13 MAK - Makerere University [Kampala, Ouganda]
14 LSHTM - London School of Hygiene and Tropical Medicine
15 University of Oxford
16 ENS de Lyon - École normale supérieure de Lyon
17 THERAVIR - Stratégies thérapeutiques contre l'infection VIH et les maladies virales associées [iPLesp]
18 UNC - University of North Carolina [Chapel Hill]
19 Harvard University
2 Rakai Health Sciences Program
3 Big Data Institute - Nuffield Department of Medicine [Oxford, UK]
4 European Molecular Biology Laboratory [Hinxton]
5 EMBL-EBI - European Bioinformatics Institute [Hinxton]
6 UCL - University College of London [London]
7 Imperial College London
8 Johns Hopkins University School of Medicine [Baltimore]
9 NIAID-NIH - National Institute of Allergy and Infectious Diseases [Bethesda]
10 Johns Hopkins Bloomberg School of Public Health [Baltimore]
11 UKZN - University of KwaZulu-Natal [Durban, Afrique du Sud]
12 Department of Statistics [Warwick]
13 MAK - Makerere University [Kampala, Ouganda]
14 LSHTM - London School of Hygiene and Tropical Medicine
15 University of Oxford
16 ENS de Lyon - École normale supérieure de Lyon
17 THERAVIR - Stratégies thérapeutiques contre l'infection VIH et les maladies virales associées [iPLesp]
18 UNC - University of North Carolina [Chapel Hill]
19 Harvard University
Vincent Calvez
- Function : Author
- PersonId : 11087
- IdHAL : vincent-calvez
- ORCID : 0000-0002-3674-1965
- IdRef : 122596943
Sarah Fidler
- Function : Author
Dan Frampton
- Function : Author
Richard Hayes
- Function : Author
Josh Herbeck
- Function : Author
Pontiano Kaleebu
- Function : Author
Cissy Kityo
- Function : Author
Jairam Lingappa
- Function : Author
Vladimir Novitsky
- Function : Author
Nick Paton
- Function : Author
Andrew Rambaut
- Function : Author
Janet Seeley
- Function : Author
Deogratius Ssemwanga
- Function : Author
Frank Tanser
- Function : Author
Tom Lutalo
- Function : Author
Ronald Galiwango
- Function : Author
Fred Makumbi
- Function : Author
Nelson Sewankambo
- Function : Author
Dorean Nabukalu
- Function : Author
Anthony Ndyanabo
- Function : Author
Joseph Ssekasanvu
- Function : Author
Hadijja Nakawooya
- Function : Author
Jessica Nakukumba
- Function : Author
Grace Kigozi
- Function : Author
Betty Nantume
- Function : Author
Nampijja Resty
- Function : Author
Jedidah Kambasu
- Function : Author
Margaret Nalugemwa
- Function : Author
Regina Nakabuye
- Function : Author
Lawrence Ssebanobe
- Function : Author
Justine Nankinga
- Function : Author
Adrian Kayiira
- Function : Author
Gorreth Nanfuka
- Function : Author
Ruth Ahimbisibwe
- Function : Author
Stephen Tomusange
- Function : Author
Ronald Galiwango
- Function : Author
Margaret Nakalanzi
- Function : Author
Joseph Otobi
- Function : Author
Denis Ankunda
- Function : Author
Joseph Ssembatya
- Function : Author
John Ssemanda
- Function : Author
Emmanuel Kato
- Function : Author
Robert Kairania
- Function : Author
Alice Kisakye
- Function : Author
James Batte
- Function : Author
James Ludigo
- Function : Author
Abisagi Nampijja
- Function : Author
Steven Watya
- Function : Author
Kighoma Nehemia
- Function : Author
Sr. Margaret Anyokot
- Function : Author
Joshua Mwinike
- Function : Author
George Kibumba
- Function : Author
Paschal Ssebowa
- Function : Author
George Mondo
- Function : Author
Francis Wasswa
- Function : Author
Agnes Nantongo
- Function : Author
Rebecca Kakembo
- Function : Author
Josephine Galiwango
- Function : Author
Geoffrey Ssemango
- Function : Author
Andrew Redd
- Function : Author
John Santelli
- Function : Author
Caitlin Kennedy
- Function : Author
Jennifer Wagman
- Function : Author
Aaron Tobian
- Function : Author
Abstract
Background: International and global organisations advocate targeting interventions to areas of high HIV prevalence (ie, hotspots). To better understand the potential benefits of geo-targeted control, we assessed the extent to which HIV hotspots along Lake Victoria sustain transmission in neighbouring populations in south-central Uganda.
Methods: We did a population-based survey in Rakai, Uganda, using data from the Rakai Community Cohort Study. The study surveyed all individuals aged 15-49 years in four high-prevalence Lake Victoria fishing communities and 36 neighbouring inland communities. Viral RNA was deep sequenced from participants infected with HIV who were antiretroviral therapy-naive during the observation period. Phylogenetic analysis was used to infer partial HIV transmission networks, including direction of transmission. Reconstructed networks were interpreted through data for current residence and migration history. HIV transmission flows within and between high-prevalence and low-prevalence areas were quantified adjusting for incomplete sampling of the population.
Findings: Between Aug 10, 2011, and Jan 30, 2015, data were collected for the Rakai Community Cohort Study. 25 882 individuals participated, including an estimated 75·7% of the lakeside population and 16·2% of the inland population in the Rakai region of Uganda. 5142 participants were HIV-positive (2703 [13·7%] in inland and 2439 [40·1%] in fishing communities). 3878 (75·4%) people who were HIV-positive did not report antiretroviral therapy use, of whom 2652 (68·4%) had virus deep-sequenced at sufficient quality for phylogenetic analysis. 446 transmission networks were reconstructed, including 293 linked pairs with inferred direction of transmission. Adjusting for incomplete sampling, an estimated 5·7% (95% credibility interval 4·4-7·3) of transmissions occurred within lakeside areas, 89·2% (86·0-91·8) within inland areas, 1·3% (0·6-2·6) from lakeside to inland areas, and 3·7% (2·3-5·8) from inland to lakeside areas.
Interpretation: Cross-community HIV transmissions between Lake Victoria hotspots and surrounding inland populations are infrequent and when they occur, virus more commonly flows into rather than out of hotspots. This result suggests that targeted interventions to these hotspots will not alone control the epidemic in inland populations, where most transmissions occur. Thus, geographical targeting of high prevalence areas might not be effective for broader epidemic control depending on underlying epidemic dynamics.
Funding: The Bill & Melinda Gates Foundation, the National Institute of Allergy and Infectious Diseases, the National Institute of Mental Health, the National Institute of Child Health and Development, the Division of Intramural Research of the National Institute for Allergy and Infectious Diseases, the World Bank, the Doris Duke Charitable Foundation, the Johns Hopkins University Center for AIDS Research, and the President's Emergency Plan for AIDS Relief through the Centers for Disease Control and Prevention.
Domains
Life Sciences [q-bio]Origin | Publication funded by an institution |
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