PurposeAs the human immunodeficiency virus (HIV) pandemic is far from over, whether there are subclinical macular changes in HIV-positive patients is something that should not be overlooked. We aimed to apply optical coherence tomography angiography (OCTA) to assess the macular structure and microvasculature changes in patients with HIV without infectious retinopathy. MethodsHIV-positive and -negative participants were included and classified into three groups: HIV-negative, HIV-positive, and HIV-positive with microvasculopathy. OCTA parameters regarding macular structure and microvasculature were analyzed. ResultsCompared with the HIV-negative group, the superficial retinal vessel density (VD) in the parafovea sectors and the whole Early Treatment of Diabetic Retinopathy Study (ETDRS) grid and the choroidal vascularity index (CVI) in the whole ETDRS grid were significantly decreased in the HIV-positive and HIV-positive with microvasculopathy groups (p < 0.05). No differences were found in OCTA parameters between the HIV-positive and HIV-positive with microvasculopathy groups. Retinal, retinal nerve fiber layer-ganglion cell layer-inner plexiform layer (RNFL-GCL-IPL), RNFL, GCL-IPL, and INL thickness showed a negative association with the duration of HIV diagnosis or antiretroviral therapy (ART) (all p < 0.05). All OCTA microvasculature parameters showed no association with HIV-related clinical variables (all p > 0.05). ConclusionsSubclinical macular changes existed in HIV-infected patients without clinical infectious retinopathy. Substructures from inner retinal layers might be associated with HIV infection or ART duration.