Antiretroviral therapy has transformed HIV into a chronic condition, enabling many people living with HIV to achieve near-normal life expectancy. However, HIV-associated complications remain common, driven by persistent immune activation, inflammation, sedentary lifestyle, and poor diet with cardiometabolic issues such as dyslipidemia, insulin resistance, body composition changes, and osteoporosis among the most prevalent. Newer antiretroviral therapy regimens, particularly integrase strand transfer inhibitor–based therapies, are better tolerated and typically associated with fewer systemic complications compared with previous therapy options. Neurocognitive impairment persists despite viral suppression and requires ongoing assessment and support. Distal sensory polyneuropathy affects up to 60% of people living with HIV, with evidence supporting treatment using gabapentin and capsaicin and possibly alpha-lipoic acid and medical cannabis in select cases. Chronic kidney disease is commonly driven by hypertension or diabetes. Rising sexually transmitted infection rates highlight the necessity of sexual health counseling and interventions such as doxycycline postexposure prophylaxis. Noninfectious pulmonary conditions such as chronic obstructive pulmonary disease and pulmonary hypertension remain underrecognized. Gastrointestinal complications are common and often worsen as CD4 counts decline. Dermatologic and hematologic complications, including cytopenias and clonal hematopoiesis, are associated with increased cancer risk. Primary care clinicians play a critical role of caring for a patient with HIV through routine screening, lifestyle counseling, and coordinated care.