‘Waves of resistance: The impact of malnutrition and mobility on art pharmacokinetics and resistance among key populations in Kalangala Islands, Uganda’

22 Background: Kalangala district is an isolated fishing community on Lake Victoria with 84 islands. The district has only 15 health facilities. However, only 8 are accredited to offer ART services. The district presents unique barriers to ART effectiveness among Key Populations (KPs). According to Uganda AIDS Commission (2024), it was ranked second with the highest HIV prevalence in Uganda (13.1) way above the National average of 5.2. High mobility in search of fish catches and widespread malnutrition is hypothesized to significantly affect ART pharmacokinetics, adherence, and drug resistance. This study examines how malnutrition and mobility impact ART drug levels, treatment outcomes and resistance patterns among KPs in Kalangala Islands. Methods: A cross-sectional study was conducted between July 2024 and January 2025, enrolling 250 Key Population living with HIV from four island-based health facilities. Participants were stratified into the following: fisherfolk (45.2%), sex workers (28.4%), people who inject drugs (15.6%) and transgender (10.8%). Pharmacokinetics analysis: Blood samples were collected at 0-, 4-, and 8 h post-dose to assess tenofovir (TFV), lamivudine (3TC) and efavirenz (EFV) levels. Therapeutic drug levels were defined as TFV ≥ 40 and EFV ≥ 1000 ng/mL. Nutritional and mobility assessment: BMI < 18.5 kg/m2 was used to classify malnutrition. About 52.8% of participants were food insecure, with 31.6% experiencing moderate malnutrition. Mobility was assessed using client locator log and self-reported travel frequency over 6 months. About 67.4% of fisherfolk travelled across islands weekly, with 12.3% missing ART refills. Adherence and resistance: ART adherence was evaluated using appoint register and a Visual Analog Scale (VAS, 0–100%). Viral resistance genotyping was performed for individuals with HIV RNA > 1000 copies/mL after 6 months on ART. Poor adherence was defined as <75% ART intake over 6 months. Results: About 41.2% of participants had suboptimal adherence (<75%), mainly due to mobility (64.7%) and food insecurity (23.5%). About 57.6% of fisherfolk and 48.9% of sex workers missed ART doses due to relocations. Individuals travelling ≥3 times/month had 2.5 times higher odds (95% CI: 1.7–3.9, p < 0.001) of missing doses. About 34.9% had sub-therapeutic ART drug levels, significantly correlated with malnutrition (p < 0.001). About 23.1% developed drug resistance mutations, with M184V (48.6%) for Lamivudine and K103N (35.2%) for Efavirenz. Malnourished participants had 3.1 times higher odds (95% CI: 2.0–4.8, p < 0.001) of sub-therapeutic ART levels and 1.9 times higher odds (p = 0.002) of developing resistance. Overall, 78.3% achieved viral suppression (HIV RNA < 400 copies/mL), significantly below the UNAIDS 95% suppression target. Conclusions: High mobility and malnutrition significantly impact ART pharmacokinetics, leading to sub-therapeutic drug levels, poor adherence and increased resistance rates among Key Populations in Kalangala Islands. Mobile fisherfolk are at the highest risk, with over 35% failing to achieve viral suppression.