LAUSR

Abstract Background Pakistan’s explosive human immunodeficiency virus (HIV) epidemic among people who inject drugs (PWID) varies widely across cities. We evaluated possible drivers for these variations. Methods Multivariable regression analyses were undertaken using data from 5 national surveys among PWID (n = 18 467; 2005–2017) to determine risk factors associated with variations in city-level HIV prevalence. A dynamic HIV model was used to estimate the population-attributable fraction (PAF; proportion of HIV infections prevented over 10 years when that risk factor is removed) of these risk factors to HIV transmission and impact on HIV incidence of reducing their prevalence. Results Regression analyses suggested that city-level HIV prevalence is strongly associated with the prevalence of using professional injectors at last injection, heroin use in last month, and injecting ≥4 times per day. Through calibrating a model to these associations, we estimate that the 10-year PAFs of using professional injectors, heroin use, and frequent injecting are 45.3% (95% uncertainty interval [UI], 4.3%–79.7%), 45.9% (95% UI, 8.1%–78.4%), and 22.2% (95% UI, 2.0%–58.4%), respectively. Reducing to lowest city-level prevalences of using professional injectors (2.8%; median 89.9% reduction), heroin use (0.9%; median 91.2% reduction), and frequent injecting (0.1%; median 91.8% reduction) in 2020 reduces overall HIV incidence by 52.7% (95% UI, 6.1%–82.0%), 53.0% (95% UI, 11.3%–80.2%), and 28.1% (95% UI, 2.7%–66.6%), respectively, over 10 years. Conclusions Interventions should focus on these risk factors to control Pakistan’s explosive HIV epidemic among PWID, including a concomitant expansion of high-coverage needle/syringe provision, opioid substitution therapy, and antiretroviral therapy.