BACKGROUND: Low birth weight (LBW, <
2500 g) is an essential indicator of neonatal death and poor infant development, but data on LBW among human immunodeficiency virus (HIV)-exposed infants in China is inadequate. OBJECTIVE: This study aimed to explore the temporal trend and factors associated with the LBW among HIV-exposed infants in Hubei province, China. METHODS: The pregnant women living with HIV in Hubei province, China between Jan 2004 and Dec 2021 were enrolled this study. Recruited HIV-positive women were provided with consultation about preventing mother-to-child transmission (PMTCT). The intervention measures for PMTCT were provided to pregnant women and HIV-exposed infants, and the LBW and HIV status of infants were followed. Collected data included women's demographic information, HIV status of sexual partner, route of HIV transmission, HBV infection, HCV infection, syphilis infection, intrapartum CD4 count, whether received antiretroviral therapy (ART), the time of ART initiation, and ART regimens during pregnancy. Multivariable logistic regression was used to analyze factors associated with the LBW. RESULTS: In total, 531 mothers (581 pregnancy events) and 581 infants were enrolled. The mean birth weight and LBW rate were 3075 ± 470.2 g and 8.4%, respectively. From 2004 to 2021, a significantly increased LBW rate (4.7-14.0%, P = .004) was observed. The use of protease inhibitor (PI)-based regimen (P = .04) and the exposure to ART in the first trimester (P = .01) were positively correlated with the increase of LBW rate. Exposure to ART in the first trimester (adjusted odds ratio [aOR] 3.64, 95%CI 1.29-10.27) and the second trimester (aOR 4.53, 95%CI 1.52-13.48), premature delivery (aOR 48.44, 95%CI 16.98-138.18), and infant with HIV infection (aOR 5.91, 95%CI 1.55-22.58) were predictors for LBW. CONCLUSIONS: The significantly increased LBW rate in our study indicated that specific attention should be paid to HIV-exposed infants in China. More importantly, our study identified significant factors that can predict the risk of LBW. Interventions targeting these risk factors may prevent LBW among pregnant women living with HIV in future research and prenatal care.