Effect of HSV-2 infection on subsequent HIV acquisition: an updated systematic review and meta-analysis Katharine J Looker, PhD, Jocelyn A R Elmes, PhD,

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Effect of HSV-2 infection on subsequent HIV acquisition: an updated systematic review and meta-analysis Katharine J Looker, PhD, Jocelyn A R Elmes, PhD, Sami L Gottlieb, MD, Joshua T Schiffer, MD, Prof Peter Vickerman, DPhil, Katherine M E Turner, PhD, Prof Marie-Claude Boily, PhD The Lancet Infectious Diseases Volume 17, Issue 12, Pages 1303-1316 (December 2017) DOI: 10.1016/S1473-3099(17)30405-X Copyright © 2017 World Health Organization Terms and Conditions

Figure 1 Study selection *The search was done in parallel by two reviewers (KJL and JARE). The results for one reviewer are shown; the results were very similar between the two reviewers. Each reviewer found eight publications to be relevant that the other reviewer did not. HSV-2=herpes simplex virus type 2. The Lancet Infectious Diseases 2017 17, 1303-1316DOI: (10.1016/S1473-3099(17)30405-X) Copyright © 2017 World Health Organization Terms and Conditions

Figure 2 Pooled adjusted RR estimates of the association between HIV incidence and exposure to HSV-2 infection Estimates for effect of both prevalent and incident HSV-2 infection on HIV acquisition (timing 1; ie, HSV-2 seroconversion was observed in a previous time interval and so definitely occurred before HIV seroconversion) are shown. Estimates are shown for women and men combined when they could not be obtained separately by sex. Multiple estimates for the same study corresponding to different study countries or areas are shown when these could not be combined or when it was not appropriate to do so (ie, countries spanning two sub-regions); however, all estimates are independent (ie, for non-overlapping study populations) within each HSV-2 exposure subcategory. Ne=number of estimates. RR=relative risk. HSV-2=herpes simplex virus type 2. *Data from these studies were obtained from reference 11. The Lancet Infectious Diseases 2017 17, 1303-1316DOI: (10.1016/S1473-3099(17)30405-X) Copyright © 2017 World Health Organization Terms and Conditions

Figure 3 Sub-pooled adjusted RR estimates of the association between HIV incidence and exposure to HSV-2 infection Estimates for effect of both prevalent and incident HSV-2 infection on HIV acquisition (timing 1; ie, HSV-2 seroconversion was observed in a previous time interval and so definitely occurred before HIV seroconversion) are shown. Estimates were added for sub-pooling if they were available by subcategories, although only independent study estimates were included within a subcategory. RR=relative risk. HSV-2=herpes simplex virus type 2. Ne=number of estimates. FSWs=female sex workers. MSM=men who have sex with men. The Lancet Infectious Diseases 2017 17, 1303-1316DOI: (10.1016/S1473-3099(17)30405-X) Copyright © 2017 World Health Organization Terms and Conditions