Research indicates the important role that informal caregivers play in improving the health and well-being of disadvantaged persons living with HIV/AIDS (PLHAs) in the United States. However, additional research is needed to understand how to reduce caregiver role overload that has the potential for distress and cessation of informal care. We used latent profile analysis and structural equation modeling (SEM) to examine the relationships among role overload, level of perceived support by network members, caregiver demographic characteristics, and social network members’ characteristics among a sample of 215 predominantly low-income, African-American informal caregivers. SEM results indicated that caregiver role overload was associated with being in the less supported group, younger age, and limited physical functioning. Interventions are needed to address the support needs of the majority of HIV caregivers, particularly physically impaired female caregivers, to improve their ability to care for themselves and reduce their potential for distress and cessation of care.