The Pathophysiology of HIV

The Short Version

Once human immunodeficiency virus (HIV) has entered the body, the virus replicates, primarily attacking lymphocytes called CD4+ T cells. Loss of these cells essentially destroys the immune system, leaving the client unable to fight off opportunistic infections. As viral load increases and CD4 cell counts drop, the danger increases. Primary cause of death is an opportunistic infection, such as respiratory arrest due to P. jiroveci pneumonia, with HIV as the underlying cause.

The Longer Version

HIV cannot replicate unless it is inside a living cell. To enter a CD4+ T cell, proteins on the envelope of the virus must bind with receptor sites on the cell. These proteins bind with CD4 receptors as well with chemokine receptors (specifically CXCR4 and CCR5 receptors, which will come up again when we talk about the relationship of genetics to HIV acquisition).

Once inside the cell, the virus begins the process of replication:

1. RNA is transcribed into DNA with help from an enzyme called reverse transcriptase.
2. The DNA strand copies itself and the two strands enter the cell's nucleus.
3. The DNA splices itself into the cell's genome with an enzyme called integrase. This means that HIV is now a permanent part of the cell. Every daughter cell will also be infected with HIV.
4. The cell produces HIV using the enzyme protease.
5. The new viruses exit the CD4 cell via budding, which eventually destroys the cell.

Here is a good illustration of viral replication, courtesy of NIAID. (Caveat: My numbering does not match theirs.)

Each step of viral replication, then, is an opportunity for treatment to stop replication. (We'll cover treatment in a future post.)

Initial infection is marked by both a high viral load and signs/symptoms resembling the flu. Then, the viral load drops for what can be a long period of time (up to ten years) without clinical symptoms. Two characteristics of this latent period make the virus especially insidious: First, an asymptomatic person is less likely to seek testing and treatment, heightening the risk that they will transmit the virus to others. Second, the virus replicates at such a fast pace that it mutates wildly, and this genetic variability hinders vaccine development.

A healthy adult has 800-1200 CD4+ T cells per microliter of blood; the immune system can function well with a CD4 count as low as 500. As HIV progresses, the body's ability to replace destroyed CD4+ T cells is overtaken by the ability of HIV to destroy those cells. When the CD4 count drops below 500, immune problems begin to occur, increasing in severity as the count continues to drop.

A client progresses to AIDS according to this classification system set out by the CDC; a person in Category 3 or Category C (or both) has AIDS. The system tracks CD4 count against the presence of opportunistic infection.

CD4 Counts	Clinical Categories
	A*	B**	C***
1. ≥500	A1	B1	C1
2. 200-499	A2	B2	C2
3. <200	A3	B3	C3

*Category A: Asymptomatic, acute HIV infection, or persistent generalized lymphadenopathy

**Category B: Symptomatic conditions that are not A or C. These are conditions attributed to HIV infection or immunosuppression; or they are conditions complicated by HIV infection. Some examples are: thrush, pelvic inflammatory disease, oral hairy leukoplakia, shingles, and peripheral neuropathy.

***Category C: AIDS-defining conditions. This long list of conditions includes: recurrent bacterial pneumonia, esophageal candidiasis, invasive cervical carcinoma, HIV-related encephalopathy, chronic herpes simplex, Kaposi's sarcoma, P. jiroveci pneumonia, progressive multifocal leukoencephalopathy, toxoplasmosis of the brain, and wasting syndrome (involuntary loss of more than 10% of body weight with chronic diarrhea).

References

1993 Revised Classification System for HIV Infection and Expanded Surveillance Case Definition for AIDS Among Adolescents and Adults. MMWR, December 18, 1992. Retrieved October 2011 from: http://www.cdc.gov/mmwr/preview/mmwrhtml/00018871.htm

HIV Replication Cycle. NIAID, 2010. Retrieved October, 2011 from: http://www.niaid.nih.gov/topics/HIVAIDS/Understanding/Biology/pages/hivreplicationcycle.aspx

Lewis, Heitkemper, Dirksen, O'Brien, & Bucher. Human immunodeficiency virus infection. Medical-Surgical Nursing: Assessment and Management of Clinical Problems. Mosby, 2007.

Primary HIV-1 infection: Pathogenesis; epidemiology and clinical manifestations. Up to Date, 2011. Retrieved October, 2011, from: http://www.uptodate.com.offcampus.lib.washington.edu/contents/primary-hiv-1-infection-pathogenesis-epidemiology-and-clinical-manifestations?source=search_result&search=hiv+pathophysiology&selectedTitle=1~150