The human immunodeficiency virus (HIV) is a retrovirus that causes the acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune system leads to life-threatening opportunistic infections. HIV infects cells that express CD4 receptors (T-helper lymphocytes, monocytes, macrophages, dendritic cells, and brain microglia). The glycoprotein (gp) 160 on HIV interacts with CD4 and binds via the gp120 subunit of gp160. Subsequently, HIV binds chemokine co-receptors (CCR5 and CXCR4). CD4 and co-receptor attachment of HIV to the target cell promotes membrane fusion via gp41 followed by internalization of HIV genetic material and enzymes to begin the replication process. The RNA virus is uncoated and converted to DNA via the enzyme reverse transcriptase. Once the DNA is transcribed the proviral DNA is integrated in host cell DNA via the enzyme integrase. Once integrated, the transcription of DNA occurs within the nucleus causing nuclear release of viral genomic RNA and mRNA. Translation of the RNA and mRNA into viral proteins occurs and are assembled by viral protease and packaged into a budding virion. Protease is responsible for cleaving a precursor polypeptide (gag-pol) into functional proteins that are necessary to produce mature, infectious virus. Figure 27-1 describes the life cycle of HIV. Once mature the virus will infect other susceptible cells causing immune system destruction with approximately 10 billion new viruses produced each day. The rapid and complex HIV replication process is prone to mistakes causing numerous mutations, which allows the virus to evade the immune response and allows antiretroviral resistance to evolve.
Life cycle of HIV. Reproduced with permission from Safrin S. Antiviral Agents. In: Katzung BG, Masters SB, Trevor AJ. eds. Basic & Clinical Pharmacology, 12e. New York, NY: McGraw-Hill; 2012:chap 49.
There are three primary modes of transmission for HIV: sexual (vaginal, anal, or oral), parenteral, and perinatal. Once infected, 40% to 90% of patients have an acute retroviral syndrome which mimics a mononucleosis-like illness with fever, pharyngitis, lymphadenopathy, weight loss, night sweat, diarrhea, and nausea. Symptoms occur for 2 to 6 weeks after exposure and persist for 2 to 10 weeks. Acute infection is associated with a high viral load and a decrease in CD4 cells, but an immune response is mounted decreasing the viral load leading to symptom resolution. Acute symptoms of HIV infection are nonspecific making the diagnosis difficult. After the acute symptoms subside, patients are asymptomatic for years until their CD4 levels decrease less than 200 μL.
HIV infection is diagnosed by a reactive enzyme-linked immunosorbent assay (ELISA) and positive confirmatory test (eg, Western blot). False negative ELISA tests occur and are attributed to new infection because antibody production takes 3 to 4 weeks after exposure and up to 6 months. Once diagnosed with HIV, a patient should receive counseling, a complete medical history, ...