Sex work or male-with-male sexual activity and the risks of HIV and hepatitis C acquisition among people who inject drugs: a global systematic review and meta-analysis

Background People who inject drugs (PWID) may engage in sexual behaviours that increase their HIV and hepatitis C virus (HCV) risk, including sex work and male-with-male sexual activity. We undertook a global systematic review to assess whether PWID who engage in these behaviours have higher HIV and HCV acquisition risks. Methods In this systematic review and meta-analysis, we searched MEDLINE, Embase, and PsycINFO for studies among PWID published between 01/01/2000 and 09/06/2026 that included estimates of the association between male-with-male sex or sex work and our primary outcomes of HIV or HCV incidence. Studies that estimated incidence by longitudinally re-testing people at risk of infection or by using assays for recent infection were eligible for inclusion. We also contacted authors for unpublished estimates. We pooled estimates using random-effects meta-analysis. We used I 2 to assess heterogeneity, and we used Egger's test to assess publication asymmetry. This review is registered with Prospero (CRD42020220884). Findings We included 57 studies comprising 164 estimates. Among men, recent male-with-male sex was associated with higher HIV acquisition (pooled incidence rate ratio (IRR):2.35; 95% CI: 1.51–3.66; I 2 : 51%).) but not HCV (IRR: 1.28; 95% CI: 0.95–1.72; I 2 : 21%). Recent sex work had a 1.72-fold (95% CI: 1.30–2.28; I 2 : 65%) and 1.59-fold (95% CI: 1.29–1.96; I 2 : 60%) higher HIV and HCV acquisition risk among all PWID, respectively. When stratified, sex work was associated with higher HIV acquisition among women (IRR: 2.30; 95% CI: 1.44–3.68; I 2 : 68%) but not men (IRR: 1.43; 95% CI: 0.92–2.22; I 2 : 51%), and was associated with HCV acquisition among men (IRR: 1.51; 95% CI: 1.22–1.87; I 2 : 0%), but not women (IRR: 1.26; 95% CI: 0.90–1.77; I 2 : 55%). For lifetime behaviours, only male-with-male sex was associated with HIV acquisition (IRR: 2.44; 95% CI: 1.18–5.02; I 2 = 87%). Results from Egger's tests did not provide evidence of asymmetry bias for our pooled estimates, while I 2 measures suggested considerable heterogeneity for many outcomes. Interpretation PWID who also engage in sex work or male-with-male sex were found to have higher HIV or HCV acquisition risks. Future research should aim to understand the mechanisms driving these associations. Funding Medical Research Council Greater Western Four Partnership Doctoral Training Partnership, Wellcome Trust, Canadian Institutes of Health Research and Medical Research Council.