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CHaPTEr 39 HIV and Acquired Immunodeficiency Syndrome 551

activity might favor HIV infection, as shown by the upregulation CLINICaL PEarLS
of CCR5 by IFN-α, which can facilitate viral entry. Chemokines
inhibit HIV infection by competing for viral binding sites. The α Acute Infection Is an Opportunity for Early
chemokine stromal cell–derived factor 1 (SDF-1) competes with Human Immunodeficiency Virus (HIV) Diagnosis
lymphotropic HIV strains for binding to CXCR4, whereas the β • Acute HIV infection is a nonspecific viral syndrome, often described
chemokines macrophage inflammatory protein 1-α (MIP1-α), as being similar to infectious mononucleosis.
MIP1-β, and RANTES compete with macrophage-tropic strains • Many patients present to a clinician at this stage, but most are not
for binding to CCR5. recognized as HIV infection.
• Irreparable damage to the host immune system occurs during this
stage of HIV infection resulting in chronic immune activation and the
CLINICAL FEATURES eventual collapse of the immune system.
• HIV viral latency is established during the acute infection as HIV DNA
If the HIV infection is left untreated, its natural history involves integrates with the host genome resulting. Integrated viral genetic
the progression through four clinical phases: acute retroviral material makes cure of HIV impossible even after prolonged viral
syndrome, asymptomatic or latent infection, symptomatic HIV suppression with antiretroviral therapy (ART).
infection, and finally AIDS. Each clinical phase correlates with • ART initiated during the acute infection can halt the destruction of
specific events in the interaction between HIV and the host the body’s memory T cells in the gut-associated lymphoid tissue
(GALT) and lead to better long-term outcomes for the patient.
immune system. A small percentage of patients become long-term • The practical importance of early therapy of acute infection remains
nonprogressors, and an even smaller percentage become elite in question because patients who are able to achieve and maintain
controllers (see Long-term nonprogressors/elite controllers). undetectable viral loads on ART do well despite having commenced
treatment long after their acute infection.
Acute HIV Infection
Soon after infection, unopposed by effective host immune
responses, HIV rapidly replicates and disseminates to lymphoid
tissues (see Immunopathogenesis: gastrointestinal system) and Symptomatic HIV Infection (pre-AIDS)
to the systemic circulation, with viremia reaching as high as 10 As the infection progresses, most individuals develop clinical
million copies per milliliter. Plasma viremia typically peaks in 3–4 symptoms. The ability of the immune system to contain viral
weeks after transmission, and then, as a result of the depletion replication is overcome, and the viral load begins to increase.
of susceptible CD4 T cells and HIV-specific immune responses, There is usually an inflection point in the CD4 T-cell curve
the virus load precipitously declines, followed by more gradual marking the start of a period of more rapid decline in CD4
decline for several weeks before reaching the set point. T-cell counts. As these counts fall, immunodeficiency, symptomatic
Clinically, the acute phase of HIV infection is manifested by disease, and AIDS eventually occur (Fig. 39.4).
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a flu-like illness, referred to as acute retroviral syndrome. Two
to 4 weeks after transmission, coinciding with the period of high End-Stage HIV Infection: AIDS
plasma viremia and dissemination of virus to lymphoid organs, As the CD4 T-cell count drops to <200 cells/µL, the immune
the majority of infected individuals experience a nonspecific system’s ability to fight infection is compromised to the extent
infectious mononucleosis–like illness that lasts from a few days
to several weeks. As the host develops HIV-specific immunity,
the virus load decreases, CD4 and CD8 T cells recover, and the
symptoms of the acute infection resolve. Although up to 90% of Number of CD4 cells
+
patients seek medical care for this illness, the nonspecific nature Plasma viral titer by 1,400
of the symptoms makes diagnosis of acute infection difficult, and 10 6 PCR or bDNA assay 1,200
most newly infected individuals are not diagnosed until much Plasma viral titer by
later. The public health implications of the acute HIV infection 10 5 culture or p24 antigen 1,000
are enormous because the risk of transmission from individuals
with acute infection appears to be much higher than that from 10 4 800
those with established infection, in part because of the high Plasma viremia 3 CD4 count
viral load in the former. 10 600
Asymptomatic HIV Infection 10 2 400
The acute infection is followed by a prolonged asymptomatic 10 1 200
or latent period that may last 8–10 years in adults but is much
shorter in children. During this time, the HIV viral load fluctuates
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around a relatively stable set point. The viral set point is a 1 5 10 12
major determinant of infectivity and risk of disease progression, Time (years)
with higher viral loads being associated with more likely viral
transmission, more rapid disease progression, and greater risk Symptoms Symptoms
of death. The host immune response is insufficient to eradicate fIG 39.4 Natural course of human immunodeficiency virus (HIV)
the infection but is enough to contain viral replication for many infection. The relationship between CD4 T-cell counts and viral
years. Although commonly thought to represent a stalemate loads over the course of infection in the absence of treatment.
between viral replication and CD4 T-cell production, this period (From Baliga CS, Shearer WT. HIV/AIDS. In: Fireman P, ed. Atlas
is actually characterized by a steady and inexorable decline of of allergy. 3rd ed. Philadelphia, PA: Elsevier Science (USA); 2005:
CD4 T cells (50–75 cells per year). p. 351–67.)