Human immunodeficiency virus (HIV) infection (infection with either HIV-1 or HIV-2) destroys CD4+ lymphocytes and impairs cell-mediated immunity, increasing risk of certain infections and cancers. Initial infection may cause nonspecific febrile illness. Risk of subsequent manifestations—related to immunodeficiency—is proportional to the level of CD4+ lymphocyte depletion. HIV can directly damage the brain, gonads, kidneys, and heart, causing cognitive impairment, hypogonadism, renal insufficiency, or cardiomyopathy. Manifestations range from asymptomatic carriage of the virus to end-stage HIV (acquired immune deficiency syndrome [AIDS]), which is defined by the presence of an AIDS-defining illness (serious opportunistic infections or cancers) or a CD4 count < 200/mcL. HIV infection can be diagnosed by antibody, nucleic acid (HIV RNA), or antigen (p24) testing. Screening should be routinely offered to all adults and adolescents ages 13 to 64. In addition, pregnant women should be tested for HIV early in each pregnancy, even if they have been screened during previous pregnancies. Treatment aims to suppress HIV replication by using combinations of ≥ 2 medications that inhibit HIV enzymes; treatment can restore immune function in most patients if suppression of replication is sustained.