Etiology

The human immunodeficiency retroviruses can be broadly divided into two groups: human immunodeficiency virus-1 (HIV-1) and HIV-2, both of which cause acquired immunodeficiency syndrome (AIDS). Infection with HIV-1 is associated with a progressive decrease in CD4 T-cell count and an increase in viral load leading to clinical AIDS. The stage of infection can be determined by measuring the patient's CD4 T-cell count and correlating clinical findings, such as AIDS-defining illnesses. HIV-2 infection has a more indolent course and is largely limited to West Africa.[15]

HIV is transmitted through blood or blood products, sexual contact, and perinatal transmission from mother to child. Transmission correlates with high levels of infectious virus in body fluids, and with the nature and duration of contact with these fluids.[16] The overwhelming majority of cisgender women contract HIV through heterosexual transmission; the Centers for Disease Control and Prevention estimates that 84% of new cases among women in 2019 were through heterosexual contact and 16% due to injection drug use (<1% occurred by other means such as perinatal exposure, blood transfusion, and risk factors not reported or identified).[4] Perinatal transmission can take place in utero, intrapartum, or postpartum through breast-feeding. Without intervention or antiretroviral therapy, rates of perinatal transmission range from 15% to 45%.[6]

Pathophysiology

In the early 1990s, a systematic examination of HIV replication within lymphoid tissues was conducted to define the pathophysiologic consequences of infection. These studies provided evidence for a continuum of destruction of various structural elements within the lymph nodes, spleen, and thymus, and supported the involvement of the thymus in viral replication. It is presumed that most T cells are destroyed after direct viral infection. In addition, apoptosis is thought to be responsible for the loss of CD4+ and CD8+ cells.[17][18][19]

Perinatal transmission is the most common mode of acquisition of HIV infection in children worldwide.[20] HIV can be transmitted throughout pregnancy, during labor and delivery, and postpartum through breast milk. In resource-rich settings where the majority of infants are not breastfed, approximately one third of perinatal transmission occurs in utero and the remainder during labor or delivery. Disease progression or clinical immune deficiency, high HIV viral load, sexually transmitted infections during pregnancy, and obstetric factors such as prolonged rupture of membranes are associated with increased perinatal transmission.[21][22]

During pregnancy, the placenta provides an important physical and immune barrier between maternal and fetal circulation. It is also thought to provide protection against in-utero transmission of HIV-1 infection.[23] The exact mechanisms of in-utero transmission are not known, but factors that disrupt placental integrity, such as chorioamnionitis, may play a role.[24][25] Viral characteristics, such as viral subtype or cellular tropism, and host genetic factors, such as HLA or chemokine receptor genotype, have been reported in some studies to influence in-utero transmission.[26][27][28][29][30][31] The majority of in-utero transmission is thought to occur late in pregnancy.[32][33] The mechanisms by which intrapartum transmission occurs are by direct access of cell-free or cell-associated virus to the infant systemic circulation through maternal-fetal transfusion. Maternal-fetal transfusion occurs during uterine contractions in labor, or by the infant swallowing HIV virus-containing genital tract fluid during delivery, with viral passage through the infant's gastrointestinal mucosa to underlying lymphoid cells followed by systemic dissemination.[20] In mothers who are not virally suppressed, breast milk contains high levels of the HIV virus, and transmission can occur at any point during lactation.[34][35][36][37] High maternal viral load (in plasma and in breast milk), breast milk immunologic factors, maternal breast pathology (such as mastitis, cracked or bleeding nipples, abscesses), and low maternal CD4 count are associated with increased risk of transmission through breast-feeding. Infant gastrointestinal pathology, such as candidiasis, may disrupt mucosal integrity and aid viral transmission.[38][39][40][41][42]

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