Simian immunodeficiency virus (SIV) and simian-human immunodeficiency virus (SHIV) infections in nonhuman primates closely approximate human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), but intrinsic viral differences limit translational relevance. A physiologically accurate HIV-1 model remains elusive. Here, we established a progressive HIV-1-like infection model using northern pig-tailed macaques (NPMs) infected with stHIV-1sv/G53D and monitored for 200 days. Results showed persistent viremia, progressive CD4+ T-cell depletion, and influenza-like symptoms, mirroring clinical features of HIV-1 infection. Infected macaques recapitulated T-cell exhaustion, innate immune activation, chronic immunosuppression, multi-organ biomarker alterations, and microbial dysbiosis. Transient and attenuated antiviral immunity may underlie this disease trajectory. In summary, this model serves as a complementary platform for validating direct antiviral strategies targeting HIV-1.