Acquired immunodeficiency syndrome (AIDS) was first recognized in 1981 as a distinct clinical entity, and human T-cell lymphotropic virus type III (HTLV-III)/lymphadenopathy-associated virus (LAV)/AIDS-associated retrovirus (ARV) is confirmed as its primary causative agent, responsible for a spectrum of immunological disorders with AIDS as the most severe clinical manifestation. The natural history of HTLV-III/LAV infection includes an asymptomatic antibody-negative period, seroconversion, and progression to AIDS (in a subset of seropositive individuals) or AIDS-related complex (ARC) characterized by subclinical immune deficiency or persistent generalized lymphadenopathy. Clinical signs indicative of AIDS encompass weight loss (>10% of body weight), chronic diarrhea (>1 month), prolonged fever (>1 month), oral candidiasis, and generalized lymphadenopathy, with the formal definition based on the occurrence of Pneumocystis carinii pneumonia or other life-threatening opportunistic infections, Kaposi's sarcoma, or malignant non-Hodgkin's lymphoma. HTLV-III/LAV exhibits a specific tropism for T-helper/inducer (OKT4+/LEU3+) lymphocytes, leading to inversion of the T4/T8 (helper/suppressor) ratio and profound cellular immunodeficiency, rendering patients highly vulnerable to opportunistic infections and neoplasia. Chemotherapeutic approaches to AIDS are based on three principal strategies: (i) treatment of intercurrent neoplasia (e.g., Kaposi's sarcoma) and opportunistic infections; (ii) reconstitution or enhancement of cellular immune functions using biological response modifiers; (iii) therapeutic targeting of HTLV-III/LAV to block steps in its replicative cycle. As the primum movens in AIDS pathogenesis, HTLV-III/LAV is the most attractive therapeutic target—its status as a retrovirus with a unique genomic structure (including gag, pol, env, sor, tat, and 3'-orf genes) and replicative cycle (involving reverse transcription, proviral integration, and viral protein synthesis) offers multiple vulnerabilities, such as reverse transcriptase. Extensive studies have identified inhibitors of reverse transcriptase (e.g., suramin, phosphonoformate, HPA-23, 3'-azido-2',3'-dideoxythymidine (AZT), and 2',3'-dideoxynucleosides) that inhibit HTLV-III/LAV reverse transcriptase activity and viral replication.