Background: Brazil offers free-of-charge antiretroviral therapy (ART) for people living with HIV (PLHIV) as well as pre-exposure prophylaxis (PrEP) to eligible individuals through its national health system. Adherence to ART and to PrEP is essential to achieving the expected benefits of virologic suppression and prevention of HIV acquisition. We explored whether food insecurity had direct effects on nonadherence to ART/PrEP. Methods: Cross-sectional web-based survey targeting adult sexual and gender minorities living in Brazil (May-September/2021) recruited through dating apps and social media. PLHIV reporting ART use and HIV-negative individuals reporting daily oral PrEP use were eligible for this analysis. Self-report of ART adherence was measured by the WebAd-Q instrument (3-items/past 7 days) plus a slider question regarding missed doses in the past month (latent outcome). Self-report of PrEP adherence was measured by the number of days the person took PrEP in the past week (binary outcome: <daily vs. daily). The 7-item Brazilian Scale of Food Insecurity (EBIA) was used to measure food insecurity (higher scores=more severe food insecurity). We used structural equation modeling (SEM) to assess the direct and indirect effects of variables on ART/PrEP nonadherence. Results: In total, 1,230 PLHIV were using ART, and 991 HIV-negative individuals were using daily oral PrEP. Median age of PLHIV was 37 years (HIV-negative: 34 years), most were cismen (97%). More PLHIV reported moderate/severe food insecurity 21% (HIV-negative: 12%). Self-report of ART nonadherence (WebAd-Q) was 45% (PrEP nonadherence: 7%). Higher socioeconomic status (latent variable measured by income, education, and sex work) had a strong negative effect on food insecurity. Among PLHIV, food insecurity (standardized coefficient [SC]:0.30, standard error [SE]:0.07, p<0.01), in addition to substance use and binge drinking in the past 6 months had direct effects on ART nonadherence. Among HIV-negative individuals, only food insecurity (SC:0.31, SE:0.13, p=0.02) had direct effect on PrEP nonadherence. Conclusions: Brazil has experienced worsening social inequalities, exacerbated by the COVID-19 pandemic, leading to increases in food insecurity especially among vulnerable populations. Our findings suggest that providing socio-economic support could directly help PLHIV by improving their quality of life, vulnerable HIV-negative individuals by preventing HIV acquisition, and ultimately populations through decreased HIV transmissions.