Within 3 to 6 weeks after initial infection, 40% to 90% of infected individuals develop an acute HIV syndrome, which is triggered by the initial spread of the virus and the host response. This phase is associated with a self-limited acute illness with nonspecific symptoms, including sore throat, myalgias, fever, weight loss, and fatigue, resembling a flulike syndrome. Rash, lymphadenopathy, diarrhea, and vomiting also may occur. This typically resolves spontaneously in 2 to 4 weeks.
As the infection spreads, the individual mounts antiviral humoral and cell-mediated immune responses. These responses are evidenced by seroconversion (usually within 3 to 7 weeks of presumed exposure) and by the appearance of virus-specific CD8+ cytotoxic T cells. HIV-specific CD8+ T cells are detected in the blood at about the time viral titers begin to fall and are most likely responsible for the initial containment of HIV infection. These immune responses partially control the infection and viral production, and such control is reflected by a drop in viremia to low but detectable levels by about 12 weeks after the primary exposure.
• Chronic phase. In the next, chronic phase of the disease, lymph nodes and the spleen are sites of continuous HIV replication and cell destruction. During this period of the disease, few or no clinical manifestations of the HIV infection are present. Therefore, this phase of HIV disease is called the clinical latency period. Although few peripheral blood T cells harbor the virus, destruction of CD4+ T cells within lymphoid tissues (up to 10% of which may be infected) continues during this phase, and the number of circulating blood CD4+ T cells steadily declines. Eventually, over a period of years, the continuous cycle of virus infection, T-cell death, and new infection leads to a steady decline in the number of
Infection of mucosal tissues
Infection established in lymphoid tissues, e.g., lymph node
Spread of infection Viremiathroughout the body
Establishment of chronic Clinical infection; virus concentrated latency in lymphoid tissues; low-level virus production
Destruction of lymphoid tissues:AIDS depletion of CD4+ T cells
Fig. 5.39 Pathogenesis of HIV-1 infection. The initial infection starts in mucosal tissues, involving mainly memory CD4+ T cells and dendritic cells, and spreads to lymph nodes. Viral replication leads to viremia and widespread seeding of lymphoid tissue. The viremia is controlled by the host immune response, and the patient then enters a phase of clinical latency. During this phase, viral replication in both T cells and macrophages continues unabated, but there is some immune containment of virus (not shown). A gradual erosion of CD4+ cells continues, and, ultimately, CD4+ T-cell numbers decline and the patient develops clinical symptoms of full-blown AIDS. CTL, Cytotoxic T lymphocyte.