We reported an HIV-naïve patient from a resource-limited area who was detected with multiple resistance sites associated with nucleoside reverse transcriptase inhibitors (NRTIs) and integrase strand transfer inhibitors (INSTIs) after the failure of the initial antiviral regimen dolutegravir/lamivudine (DTG/3TC) and subsequent Bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). On May 8, 2021, a 53-year-old man was diagnosed with AIDS, Marneffei talaromycosis and fungal esophagitis, and was suspected of having tuberculosis (TB) in Guangxi, China. His baseline HIV RNA was 559,000 copies/mL and the CD4 count was 12 cells/µL, but resistance genotype testing was not performed. The patient remained immunosuppressed (CD4 count 3 cells/µL) after 12 weeks of initial antiviral treatment (ART) with DTG/3TC. After he was switched to BIC/FTC/TAF and started anti-TB treatment, the viral load (HIV RNA 163,200 copies/mL) was not effectively controlled, and there were multiple NRTIs drug-resistant mutations (D67N, K70R, M184V, T215V, K219Q) and INSTIs mutations (E138K, G140A, S147SG, Q148R). This suggested that in resource-limited areas, for HIV-naïve patients in advanced stages with active opportunistic infections, HIV RNA>500,000 copies/mL, and low CD4 count, baseline resistance testing and increased HIV RNA testing frequency should be recommended, DTG/3TC was not recommended as initiation, and opportunistic infections should be treated promptly. In addition, switching to other INSTIs was not recommended in the absence of resistance testing and ineffective use of DTG.