Nello Blaser1, Celina Wettstein, Janne Estill, Luisa Salazar Vizcaya, Gilles Wandeler, Matthias Egger, Olivia Keiser. 1. aInstitute of Social and Preventive Medicine (ISPM), University of Bern bDepartment of Infectious Diseases, University Hospital Bern, Bern, Switzerland cDepartment of Infectious Diseases, University of Dakar, Dakar, Senegal dSchool of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa.
Abstract
OBJECTIVES: HIV 'treatment as prevention' (TasP) describes early treatment of HIV-infected patients intended to reduce viral load and transmission. Crucial assumptions for estimating TasP's effectiveness are the underlying estimates of transmission risk. We aimed to determine transmission risk during primary infection, and describe the relation of HIV transmission risk to viral load. DESIGN: A systematic review and meta-analysis. METHODS: We searched PubMed and Embase databases for studies that established a relationship between viral load and transmission risk, or primary infection and transmission risk, in serodiscordant couples. We analysed assumptions about the relationship between viral load and transmission risk, and between duration of primary infection and transmission risk. RESULTS: We found 36 eligible articles, based on six different study populations. Studies consistently found that higher viral loads lead to higher HIV transmission rates, but assumptions about the shape of this increase varied from exponential increase to saturation. The assumed duration of primary infection ranged from 1.5 to 12 months; for each additional month, the log10 transmission rate ratio between primary and asymptomatic infection decreased by 0.40. CONCLUSION: Assumptions and estimates of the relationship between viral load and transmission risk, and the relationship between primary infection and transmission risk, vary substantially and predictions of TasP's effectiveness should take this uncertainty into account.
OBJECTIVES: HIV 'treatment as prevention' (TasP) describes early treatment of HIV-infectedpatients intended to reduce viral load and transmission. Crucial assumptions for estimating TasP's effectiveness are the underlying estimates of transmission risk. We aimed to determine transmission risk during primary infection, and describe the relation of HIV transmission risk to viral load. DESIGN: A systematic review and meta-analysis. METHODS: We searched PubMed and Embase databases for studies that established a relationship between viral load and transmission risk, or primary infection and transmission risk, in serodiscordant couples. We analysed assumptions about the relationship between viral load and transmission risk, and between duration of primary infection and transmission risk. RESULTS: We found 36 eligible articles, based on six different study populations. Studies consistently found that higher viral loads lead to higher HIV transmission rates, but assumptions about the shape of this increase varied from exponential increase to saturation. The assumed duration of primary infection ranged from 1.5 to 12 months; for each additional month, the log10 transmission rate ratio between primary and asymptomatic infection decreased by 0.40. CONCLUSION: Assumptions and estimates of the relationship between viral load and transmission risk, and the relationship between primary infection and transmission risk, vary substantially and predictions of TasP's effectiveness should take this uncertainty into account.
Authors: C Celum; A Wald; J R Lingappa; A S Magaret; R S Wang; N Mugo; A Mujugira; J M Baeten; J I Mullins; J P Hughes; E A Bukusi; C R Cohen; E Katabira; A Ronald; J Kiarie; C Farquhar; G J Stewart; J Makhema; M Essex; E Were; K H Fife; G de Bruyn; G E Gray; J A McIntyre; R Manongi; S Kapiga; D Coetzee; S Allen; M Inambao; K Kayitenkore; E Karita; W Kanweka; S Delany; H Rees; B Vwalika; W Stevens; M S Campbell; K K Thomas; R W Coombs; R Morrow; W L H Whittington; M J McElrath; L Barnes; R Ridzon; L Corey Journal: N Engl J Med Date: 2010-01-20 Impact factor: 91.245
Authors: Noah Kiwanuka; Oliver Laeyendecker; Thomas C Quinn; Maria J Wawer; James Shepherd; Merlin Robb; Godfrey Kigozi; Joseph Kagaayi; David Serwadda; Fred E Makumbi; Steven J Reynolds; Ronald H Gray Journal: AIDS Date: 2009-11-27 Impact factor: 4.177
Authors: Zhong-Min Ma; Mars Stone; Mike Piatak; Becky Schweighardt; Nancy L Haigwood; David Montefiori; Jeffrey D Lifson; Michael P Busch; Christopher J Miller Journal: J Virol Date: 2009-01-07 Impact factor: 5.103
Authors: Marie-Claude Boily; Rebecca F Baggaley; Lei Wang; Benoit Masse; Richard G White; Richard J Hayes; Michel Alary Journal: Lancet Infect Dis Date: 2009-02 Impact factor: 25.071
Authors: J F G Monteiro; D J Escudero; C Weinreb; T Flanigan; S Galea; S R Friedman; B D L Marshall Journal: Epidemiol Infect Date: 2016-01-12 Impact factor: 2.451
Authors: Ann M Dennis; Shuntai Zhou; Christopher J Sellers; Emily Learner; Marc Potempa; Myron S Cohen; William C Miller; Joseph J Eron; Ronald Swanstrom Journal: J Infect Dis Date: 2018-10-20 Impact factor: 5.226
Authors: Mansour Farahani; Vladimir Novitsky; Rui Wang; Hermann Bussmann; Sikhulile Moyo; Rosemary M Musonda; Themba Moeti; Joseph M Makhema; Max Essex; Richard Marlink Journal: AIDS Res Hum Retroviruses Date: 2016-03-03 Impact factor: 2.205
Authors: A Hahn; R Hinz; T Meyer; U Loderstädt; O Herchenröder; C G Meyer; N G Schwarz; H Frickmann Journal: Epidemiol Infect Date: 2018-04-15 Impact factor: 4.434
Authors: María Julia Ruiz; Jimena Salido; Lorena Abusamra; Yanina Ghiglione; Cintia Cevallos; Gabriel Damilano; Ana María Rodriguez; César Trifone; Natalia Laufer; Luis D Giavedoni; Omar Sued; Horacio Salomón; María Magdalena Gherardi; Gabriela Turk Journal: EBioMedicine Date: 2017-11-03 Impact factor: 8.143
Authors: Eugène D M B Kroon; Nittaya Phanuphak; Andrew J Shattock; James L K Fletcher; Suteeraporn Pinyakorn; Nitiya Chomchey; Siriwat Akapirat; Mark S de Souza; Merlin L Robb; Jerome H Kim; Frits van Griensven; Jintanat Ananworanich; David P Wilson Journal: J Int AIDS Soc Date: 2017-06-28 Impact factor: 5.396