The cause of acquired immunodeficiency syndrome (AIDS) is the human immunodeficiency virus (HIV), a single-stranded RNA virus of the retrovirus family that produces a reverse transcriptase enabling the viral RNA to act as a template for DNA transcription and integration into the host genome. HIV-1 causes 99% of all human cases. HIV-2, which is less virulent, causes 1% to 9% of cases in parts of Africa and is very rare in the United States.
HIV infects helper T cells (CD4 cells) and cells of monocyte-macrophage lineage via interaction of viral protein gp120 with the CD4 molecule and chemokines (CXCR4 on T cells and CCR5 on dendritic cells and macrophages) that serve as coreceptors. Interaction with these molecules facilitates membrane fusion and cell entry by the virus. HIV infection directly and indirectly depletes CD4 T cells. Because helper T cells are important for delayed hypersensitivity, T cell–dependent B cell antibody production, and T cell–mediated lymphokine activation of macrophages, their destruction produces a profound combined (B and T cell) immunodeficiency. A lack of T cell regulation and unrestrained antigenic stimulation result in polyclonal hypergammaglobulinemia with nonspecific and ineffective globulins. Other cells bearing CD4, such as microglia, astrocytes, oligodendroglia, and placental tissues also may be infected with HIV.
HIV infection is a continuously progressive process with a variable period of clinical latency before development of AIDS-defining conditions. All untreated patients have evidence of ongoing viral replication and progressive CD4 lymphocyte depletion. There are no overt manifestations of immunodeficiency until CD4 cell numbers decline to critical threshold levels. Quantitation of the viral load has become an important parameter in management.
Horizontal transmission of HIV is by sexual contact (vaginal, anal, or orogenital), percutaneous contact (from contaminated needles or other sharp objects), or mucous membrane exposure to contaminated blood or body fluid. Transmission by contaminated blood and blood products has been eliminated in developed countries but still occurs in developing countries. Vertical transmission of HIV from mother to infant may occur transplacentally in utero, during birth, or by breastfeeding. Risk factors for perinatal transmission include prematurity, rupture of membranes more than 4 hours, and high maternal circulating levels of HIV at delivery. Perinatal transmission can be decreased from approximately 25% to less than 8% with antiretroviral treatment of the mother before and during delivery and postnatal treatment of the infant. Breastfeeding by HIV-infected mothers increases the risk of vertical transmission by 30% to 50%. In untreated infants, the mean incubation interval for development of an AIDS-defining condition after vertical transmission is 5 months (range, 1 to 24 months) compared with a longer incubation period after horizontal transmission of 7 to 10 years.
Worldwide, as of 2010, approximately 34 million persons are living with HIV and 3.4 million of them are children. Therewere 2.7 million new infections in 2010 with approximately390,000 new infections in children. Roughly 70% of all people living with HIV reside in sub-Saharan Africa. Worldwide, 1.8 million people died from HIV-related illnesses in 2010. In2010 the estimated number of people over the age of 13 yearsand living with HIV in the United States was 1.1 million, and approximately 9800 children are infected. Vertical transmission is much less common than previously, and approximately50 infants are born with HIV infection each year in the UnitedStates. Most pediatric cases now occur in adolescents whoengage in unprotected sexual activities. Worldwide the numberof deaths related to HIV and the number of children infected with HIV have steadily decreased in large part due to treatmentwith antiretroviral therapy.