Fig. 5.40 ClinicalcourseofHIVinfection.(A)Duringtheearlyperiodafterprimaryinfection,thereisdisseminationofvirus,developmentofanimmuneresponsetoHIV,andoftenanacuteviralsyndrome.Duringtheperiodofclinicallatency,viralreplicationcontinuesandtheCD4+ T-cellcountgraduallydecreases,untilitreachesacriticallevelbelowwhichthereisasubstantialriskforAIDS-associateddiseases.(B)ImmuneresponsetoHIVinfection.AcytotoxicT-lymphocyte(CTL)responsetoHIVisdetectableby2to3weeksaftertheinitialinfection,anditpeaksby9to12weeks.Markedexpansionofvirus-specificCD8+ T-cellclonesoccursduringthistime,andupto10%ofapatient’sCTLsmaybeHIVspecificat12weeks.ThehumoralimmuneresponsetoHIVpeaksatabout12weeks.(A, Redrawn from Fauci AS, Lane HC: Human immunodeficiency virus disease: AIDS and related conditions. In Fauci AS, et al, editors: Harrison’sprinciplesofinternalmedicine, ed 14, New York, 1997, McGraw-Hill, p 1791.)
CD4+ T cells in the lymphoid tissues and the circulation.
• AIDS. The final phase is progression to AIDS, characterized by a breakdown of host defense, a dramatic increase in plasma virus, and severe, life-threatening clinical disease. Typically the patient presents with long-lasting fever (>1 month), fatigue, weight loss, and diarrhea. After a variable period, serious opportunistic infections, secondary neoplasms, or clinical neurologic disease (grouped under the rubric AIDS indicator diseases or AIDS-defining illnesses, discussed later) emerge, and the patient is said to have developed AIDS.
The extent of viremia, measured as HIV-1 RNA levels in the blood, is a useful marker of HIV disease progression and is of value in the management of HIV-infected individuals. The viral load at the end of the acute phase reflects the equilibrium reached between the virus and the host response, and in a given patient it may remain fairly stable for several years. This level of steady-state viremia, called the viral set point, is a predictor of the rate of decline of CD4+ T cells and, therefore, progression of HIV disease.
10 years or more, with stable CD4+ T cell counts and low levels of plasma viremia (usually <500 viral RNA copies/ mL). Remarkably, about 1% of infected individuals have undetectable plasma virus (<50 to 75 RNA copies/mL); these have been called elite controllers. Individuals with such an uncommon clinical course have attracted great attention in the hope that studying them may shed light on host and viral factors that influence disease progression. Studies thus far indicate that this group is heterogeneous with respect to the variables that influence the course of the disease. In most cases, the viral isolates do not show qualitative abnormalities, suggesting that the uneventful course cannot be attributed to a “wimpy” virus. In all cases, there is evidence of a vigorous anti-HIV immune
Table 5.15 CDC Classification Categories of HIV Infection
Because the loss of immune containment is associated with declining CD4+ T cell counts, the Centers for Disease Control and Prevention (CDC) classification of HIV infection stratifies patients into three groups based on CD4+ cell counts: greater than or equal to 500 cells/µL, 200 to 499 cells/µL, and fewer than 200 cells/µL (
Table 5.15