Porth's Essentials of Pathophysiology, 4e

366

Infection and Immunity

U N I T 4

TABLE 16-2 The Revised CDC Classification System for Human ImmunodeficiencyVirus (HIV) Infection in Adults and Adolescents Aged 13Years. *

CD4 +  T-cell Count Cells/μL (CD4 +  T-cell Percentage)

Stage

AIDS-defining Conditions (ADC)

≥ 500 (29%)

Stage 1 Stage 2 Stage 3

No ADC No ADC

200–499 (14%–28%)

<200 (<14%)

No documented ADC

Stage undetermined

No information

No information

*A confirmed case meets the laboratory diagnosis of HIV infection and one of the four stages. Although cases with no information on AIDS-defining characteristics can be classified as stage unknown, every effort should be made to obtain CD4 + T-cell counts and percentages and the presence of AIDS-defining conditions at the time of diagnosis. Developed from Schneider E, Whitmore S, Glynn KM, et al., for the Centers for Disease Control and Prevention (CDC). Revised case definitions for HIV infections among adults, adolescents, and children aged <18 months and for children aged 18 months to <13 years—United States, 2008. MMWR Recomm Rep. 2008;57(RR-10):1–12.

The primary stage is followed by a latent period (stage 2) during which the person has no signs or symptoms of illness. The median time of the latent period is about 10 years. During this time, the CD4 + T-cell count falls gradually from the normal range of 800 to 1000 cells/ μ L to 200 to 499 cells/ μ L (14% to 28%). More recent data suggest that the CD4 + T-cell decline may not fall in an even slope based on HIV RNA levels, and factors related to the variability in the decline in CD4 + T cells are under investigation. 59 Lymphadenopathy (i.e., swol- len lymph nodes) for more than 3 months in at least two locations (not including the groin) develops in some per- sons with HIV infection during this phase. The lymph nodes may be sore or visible externally. Stage 3 (overt AIDS) occurs when a person has a CD4 + T-cell count of less than 200 cells/ μ L (<14%) or an AIDS- defining illness. 60 Without antiretroviral therapy, this phase can lead to death within 2 to 3 years. The risk of opportunistic infections and death increases significantly when the CD4 + T-cell count falls below 200 cells/ μ L.

The clinical course of HIV varies from person to person. In the absence of treatment, most people with HIV infection progress to AIDS after 7 to 10 years. 2,60 These people are the chronic or typical progressors. Another 10% to 20% are rapid progressors who develop AIDS within 2 to 3 years after primary infec- tion. The final 5% to 15% are long-term nonprogres- sors, who remain asymptomatic for 10 years or more after seroconversion, with stable CD4 + T-cell counts and low plasma HIV RNA levels. A subset of these long-term nonprogressors, called elite controllers, have plasma HIV RNA levels that are below the level of detection. Studies of these individuals have helped to identify host and viral factors that influence disease progression. 2 One factor found to be important in elite control is a mutation in the genes coding for CCR5, a coreceptor used for HIV entry. Mutations in both genes result in CD4 + cells with a defective CCR5, thereby preventing HIV entry into those cells. Research in this area is ongoing.

Levels of viral load and CD4 immune response

viral load CD4 T-lymphocyte count +

+

HIV-1 exposure

2–4 weeks Acute clinical syndrome

2–3 years Overt AIDS

8–10 years Latency

FIGURE 16-9. Viral load and CD4 + cell count during the phases of HIV infection. AIDS, acquired immunodeficiency syndrome; HIV, human immunodeficiency virus.