SECTION

12 VIRAL LOAD, IMMUNE RESPONSE, AND TIMING OF DETECTION DURING THE PHASES OF HIV-1 INFECTION
Infections, Infestations, and Bites

Levels of viral
load and
immune Peak
response viremia

HIV-1
exposure

Days 10 20 30 40 50 5–10 years 2–3 years

Phase of clinical latency Overt AIDS

Severe constitutional
Viral detection: NAT Late appearance of constitutional symptoms
symptoms Opportunistic infections
p24 detection: 4th Neoplasms
generation immunoassay

P24 antigen
Antibody detection: 3rd
generation immunoassay Plasma viremia
HIV antibody
Antibody detection: 2nd
CD4+ T-lymphocyte
generation & HIV-1/-2
count
differentiation immunoassays

Acute retroviral syndrome

Fig. 78.3 Viral load, immune response, and timing of detection during the phases of HIV-1 infection. After HIV-1 exposure, initial virus replication and spread
 

occur in the lymphoid organs, and systemic dissemination of HIV-1 is reflected by the peak of plasma viremia. A clinical syndrome of varying severity is associated
with this phase of primary HIV-1 infection in up to 80% of HIV-1-infected persons. Down-regulation of viremia during the transition from the primary to the early
chronic phase coincides with the appearance of HIV-1-specific cytotoxic T lymphocytes and with the progressive resolution of the clinical syndrome. The long
phase of clinical latency is associated with active virus replication, particularly in the lymphoid tissue. During the clinically latent period, CD4+ T-lymphocyte counts
slowly decrease, as does the HIV-1-specific immune response. When CD4+ T-lymphocyte counts decrease below 200 cells/ml (i.e. when overt AIDS occurs), the
clinical picture is characterized by severe constitutional symptoms and by the possible development of opportunistic infections and/or neoplasms. Adapted from Bart
PA, Pantaleo G. The immunopathogenesis of HIV-1 infection. In: Cohen J, Powderly WG. Infectious Diseases. Edinburgh: Mosby, 2004:1236.

development of HIV-1 antibodies. Up to 80% of newly infected indi-
viduals develop an “acute retroviral syndrome” resembling influenza or
mononucleosis. Symptoms develop 2–6 weeks after HIV exposure and
often include fever, headache, myalgia/arthralgia, pharyngitis, lymph-
adenopathy, and night sweats. A morbilliform exanthem also occurs in
40–80% of patients; it lasts 4–5 days and is typically generalized, with
the most prominent involvement on the face and trunk. Oral and
genital ulcers are occasionally present. Symptoms are self-limited and
resolve in a few days to weeks, with a median duration of 14 days. The
initial phase of rapid HIV-1 replication causes a temporary fall in CD4+
cell counts, occasionally to an extent that gives rise to opportunistic
infections.
Greater severity and longer duration of the acute retroviral syndrome
is associated with a higher viral load set point and more rapid disease
progression16. Early initiation of ART during primary HIV infection
may delay disease progression17.
Herpes simplex virus (HSV)
Relatively immunocompetent HIV-infected individuals usually have
typical, self-limited HSV disease. As immunity wanes, the frequency
of HSV recurrences increases and lesions take longer to heal, potentially
1368 evolving into chronic, extensive, deep, and painful ulcers that favor the
perianal region, genitalia, and tongue (Fig. 78.4). Atypical presentations
of HSV infection include folliculitis, verrucous plaques, and hypertro-
phic anogenital masses simulating neoplasia. Infection may become
disseminated or occur at unusual sites such as the non-keratinized
(unattached) mucosa of the oropharynx (see Fig. 72.1) and the
esophagus.
The ulcer edge should be scraped for HSV PCR (most sensitive),
direct fluorescent antibody assay (DFA), and/or viral culture and, if
negative, a skin biopsy performed; a Tzanck smear has low sensitivity.
Higher doses and longer courses of antiviral medications are typically
required, with continuation until all mucocutaneous lesions are healed.
Resistance to acyclovir, usually due to reduced viral thymidine kinase
activity, occurs more commonly in immunosuppressed (~5%) com-
pared to immunocompetent (~1%) hosts. Alternative agents that do
not rely on thymidine kinase include foscarnet, cidofovir, and imiqui-
mod18. Of note, HSV-2 can also promote HIV-1 replication19.
Varicella–zoster virus (VZV)
In HIV-infected individuals, varicella tends to have new lesion forma-
tion over a longer period of time, a higher lesion count, and (particularly
in adults) complications such as pneumonitis, hepatitis, and encepha-
litis. Lesions that persist as slowly healing ulcers have been reported.
HIV-infected individuals have a 7–15-fold higher incidence of herpes
zoster compared to the general population20. In addition to classic