Page 36 - AIDSBK23C

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health, can be variable--from as short as 18 months to over 15 years. This latent period lasts, on
average, from 8 to 10 years.[21,54]
There is evidence that the thymus may retain some capacity to produce new T
lymphocytes, even into adulthood, and that HIV could affect the dynamics of thymic function.
A surrogate marker for thymic activity is the T-cell receptor excision circle (TREC) that is the
result of the splicing of the variable (V), diversity (D) and joining (J) regions of the T-cell
receptor (TCR) gene. TRECs are almost exclusively of thymic origin, are stable and do not
degrade easily over time, and do not divide when a cell divides. Indeed, TREC may increase in
chronically infected HIV patients who receive antiretroviral therapy.[204]
Emergence of HIV infection from clinical latency is marked by a decline in the CD4
lymphocyte count and an increase in viremia. Replication of HIV increases as the infection
progresses. There is loss of normal lymph node architecture as the immune system fails. Before
serologic and immunologic markers for HIV infection became available, clinical criteria
established emergence from latency by development of generalized lymphadenopathy. This
condition, described by the term persistent generalized lymphadenopathy (PGL), is not life-
threatening.[22]
Another phase of HIV infection described clinically but no longer commonly diagnosed
in practice, is the condition known as AIDS-related complex (ARC), which is not necessarily
preceded by PGL. ARC lacks only the opportunistic infections and neoplasms, which define
AIDS. ARC patients usually show symptoms of fatigue, weight loss, and night sweats, along
with superficial fungal infections of the mouth (oral thrush) and fingernails and toenails
(onychomycosis). It is uncommon for HIV-infected persons to die at the stage of ARC. The
staging of HIV disease progression with CD4 lymphocyte counts and plasma HIV-1 RNA levels
has made use of the terms PGL and ARC obsolete.[22]
The stage of clinical AIDS that is reached years after initial infection is marked by the
appearance of one or more of the typical opportunistic infections or neoplasms diagnostic of
AIDS by definitional criteria. The progression to clinical AIDS is also marked by the
appearance of syncytia-forming (SI) variants of HIV in about half of HIV-infected patients.
These SI viral variants, derived from non-syncytia-forming (NSI) variants, have greater CD4+
cell tropism and are associated with more rapid CD4+ cell decline. The SI variants typically
arise in association with a peripheral blood CD4 lymphocyte count between 400 and 500/µL,
prior to the onset of clinical AIDS. However, appearance of the SI phenotype of HIV is a marker
for progression to AIDS that is independent of CD4+ cell counts.[87]
HIV superinfection can and does occur by subtypes of HIV different from the original
infecting strain. This can have implications for disease progression, treatment, and viral
evolution. The adaptive immune response following infection with HIV may prevent a
superinfection from becoming productive. Conversely, a lack of heterologous neutralizing
antibodies may predispose to superinfection. Superinfection may be suspected with any of the
following: sudden increase in viral load, udden drop in CD4 cell count, or recurrence of acute
HIV symptoms. The most optimal period for a second infection appears to be restricted to a
window period of less than 3 years after the initial infection, with the first few months after
primary infection the most favorable for superinfection. Superinfections have been reported to
occur during treatment interruptions. The incidence of HIV superinfections is mainly controlled
by risk exposure, which consists of two aspects: risk behavior and HIV prevalence.
Superinfections increase when HIV-1 prevalence goes up. In most, but not all superinfected
patients, the second infection leads to faster disease progression. HIV superinfection can