HIV infection pathophysiology

Associate Editors-In-Chief: Ujjwal Rastogi, MBBS [mailto:urastogi@perfuse.org]

Overview
Infection with HIV-1 is associated with a progressive decrease of the CD4+ T cell count and an increase in viral load. The stage of infection can be determined by measuring the patient's CD4+ T cell count, and the level of HIV in the blood.

Pathophysiology
[[Image:Hiv-timecourse.png|400px|thumb|right|A generalized graph of the relationship between HIV copies (viral load) and CD4 counts over the average course of untreated HIV infection; any particular individual's disease course may vary considerably.

]] The initial infection with HIV generally occurs after transfer of body fluids from an infected person to an uninfected one. The first stage of infection, the primary, or acute infection, is a period of rapid viral replication that immediately follows the individual's exposure to HIV leading to an abundance of virus in the peripheral blood with levels of HIV commonly approaching several million viruses per mL. This response is accompanied by a marked drop in the numbers of circulating CD4+ T cells. This acute viremia is associated in virtually all patients with the activation of CD8+ T cells, which kill HIV-infected cells, and subsequently with antibody production, or seroconversion. The CD8+ T cell response is thought to be important in controlling virus levels, which peak and then decline, as the CD4+ T cell counts rebound to around 800 cells per mL (the normal value is 1200 cells per mL ). A good CD8+ T cell response has been linked to slower disease progression and a better prognosis, though it does not eliminate the virus. During this period (usually 2-4 weeks post-exposure) most individuals (80 to 90%) develop an influenza or mononucleosis-like illness called acute HIV infection, the most common symptoms of which may include fever, lymphadenopathy, pharyngitis, rash, myalgia, malaise, mouth and esophagal sores, and may also include, but less commonly, headache, nausea and vomiting, enlarged liver/spleen, weight loss, thrush, and neurological symptoms. Infected individuals may experience all, some, or none of these symptoms. The duration of symptoms varies, averaging 28 days and usually lasting at least a week. Because of the nonspecific nature of these symptoms, they are often not recognized as signs of HIV infection. Even if patients go to their doctors or a hospital, they will often be misdiagnosed as having one of the more common infectious diseases with the same symptoms. Consequently, these primary symptoms are not used to diagnose HIV infection as they do not develop in all cases and because many are caused by other more common diseases. However, recognizing the syndrome can be important because the patient is much more infectious during this period.

A strong immune defense reduces the number of viral particles in the blood stream, marking the start of the infection's clinical latency stage. Clinical latency can vary between two weeks and 20 years. During this early phase of infection, HIV is active within lymphoid organs, where large amounts of virus become trapped in the follicular dendritic cells (FDC) network. The surrounding tissues that are rich in CD4+ T cells may also become infected, and viral particles accumulate both in infected cells and as free virus. Individuals who are in this phase are still infectious. During this time, CD4+ CD45RO+ T cells carry most of the proviral load.

When CD4+ T cell numbers decline below a critical level, cell-mediated immunity is lost, and infections with a variety of opportunistic microbes appear. The first symptoms often include moderate and unexplained weight loss, recurring respiratory tract infections (such as sinusitis, bronchitis, otitis media, pharyngitis), prostatitis, skin rashes, and oral ulcerations. Common opportunistic infections and tumors, most of which are normally controlled by robust CD4+ T cell-mediated immunity then start to affect the patient. Typically, resistance is lost early on to oral Candida species and to Mycobacterium tuberculosis, which leads to an increased susceptibility to oral candidiasis (thrush) and tuberculosis. Later, reactivation of latent herpes viruses may cause worsening recurrences of herpes simplex eruptions, shingles, Epstein-Barr virus-induced B-cell lymphomas, or Kaposi's sarcoma, a tumor of endothelial cells that occurs when HIV proteins such as Tat interact with Human Herpesvirus-8. Pneumonia caused by the fungus Pneumocystis jirovecii is common and often fatal. In the final stages of AIDS, infection with cytomegalovirus (another herpes virus) or Mycobacterium avium complex is more prominent. Not all patients with AIDS get all these infections or tumors, and there are other tumors and infections that are less prominent but still significant.