Abstract
BACKGROUND: Transmission of drug-resistant HIV strains to treatment-naïve patients can compromise antiretroviral therapy (ART) effectiveness and lead to treatment failure. In Pakistan, transmitted HIV drug resistance among people who inject drugs (PWID) is fuelled by a lack of harm reduction, ART, poor drug adherence, and unsafe injection practices, resulting in efficient transmission in large injecting networks. METHODS: A cross-sectional study was conducted among PWID recruited in Karachi, Larkana, Peshawar, Quetta and Hyderabad (August to December 2014). A portion of the HIV pol gene was amplified from HIV-reactive dried blood spot specimens (n = 282/367) and sequenced using an in-house Sanger sequencing assay for HIV drug resistance mutation (DRM) genotyping. DRMs were identified using the Stanford University HIV Drug Resistance Database (https://hivdb.stanford.edu/hivdb). RESULTS: Overall, HIV subtype A1 was dominant (78.0%; n = 220), followed by CRF02_AG (15.6%; n = 44), CRF35_AD (2.5% n = 7), recombinants (3.5%; n = 10), and subtype C (0.4% n = 1). DRM analysis identified that over half (63.8%) of participants harboured at least one DRM, of which 28.9% reported using help from a professional injector. Nearly all (99.4%) participants were not actively receiving ART because most (88.7%) had never undergone HIV testing and were unaware of their status. CONCLUSIONS: Findings suggest significant transmitted HIV drug resistance present among PWID, exacerbated by unsafe injection practices, particularly professional injection. Low testing rates signal a need for more comprehensive testing programs to improve HIV status awareness and ART coverage in Pakistan. These gaps remain especially urgent given persistent challenges in the national response, including low ART coverage, poor adherence, and limited access to genotypic resistance testing.