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Herpes Zoster and Its Complications among HIV Patients in the HAART
Era
By
Ronald Baker, PhD
Background
 |
| A
classical pattern for shingles. The infection follows a nerve
root from the spine, along a rib, to the front of the chest.
The area innervated by the nerve is called a "dermatome". |
Herpes zoster
is an acute, localized infection that causes a painful, blistering
rash. Commonly known as "shingles," herpes zoster is caused
by the varicella-zoster virus (VZV), the same virus that causes
chickenpox. After an episode of chickenpox, the virus becomes dormant
in the body. Herpes zoster occurs as a result of the virus reactivating,
usually years after the original outbreak.
The cause of the reactivation
is not known, but it appears related to aging, stress or an impaired
immune system, such as in persons with chronic
HIV infection. Some individuals experience only a
single outbreak. However, when it is reactivated, the infection
spreads along the nerve tract, first causing pain or a burning sensation.
Because
of the layout of the nerves that herpes zoster resides in, it only
affects one side of the body or face during an outbreak.
It
begins as a rash that leads to blisters and sores on the skin.
When the nerve branch that supplies the eye is involved, the forehead,
nose, and eyelids may also be affected. Sores on the nose
are a key signal of possible eye involvement.
Many
who experience this herpes zoster infection find it extremely painful.
This acutely painful phase usually lasts several weeks; however,
some continue to experience pain or neuralgia long after the outbreak
has cleared. This is known as post-herpetic neuralgia (PHN).
Treatment
For dermatomal (skin-related) herpes zoster, the preferred treatment
for herpes zoster is IV or oral acyclovir (ACV). The alternative
therapy is IV foscarnet. For disseminated, ophthalmic nerve involvement
or visceral zoster, IV ACV is first-line and IV foscarnet is the
alternative. For ACV-resistant strains, IV foscarnet is the preferred
agent. Oral ACV is recommended for maintenance therapy.
For
post herpetic neuralgia, nortriptyline or amitriptyline is recommended,
although some patients may require pain medication.
 |
| Shingles,
or herpes zoster, is caused by the same virus that causes chickenpox.
The virus can lie dormant in the body for many years and re-emerge
as shingles. |
Herpes Zoster in the HAART Era
Not
much is known about herpes zoster its complications in the post-HAART era. Dr.
Kelly Gebo and colleagues at Johns Hopkins University School of
Medicine in Baltimore, MD conducted a retrospective cohort study
of patients enrolled in an urban HIV clinic between January 1, 1997
and December 31, 2001. The researchers evaluated the incidence,
risk factors and clinical manifestations of herpes zoster in the
general population and in HIV patients in the current era of HAART.
Summarized here are results of the Johns Hopkins study, which is
published in the October 1, 2005 issue of Journal of Acquired
Immune Deficiency Syndrome (JAIDS) [1].
In
the general population the incidence of herpes zoster virus (HZV)
infection is 1.5 to 3 per 1000. It is seen more frequently in patients
aged 60 years and older than in individuals aged less than 60 years
[2-5]. It has been observed in several studies that individuals
with HIV infection have significantly higher herpes zoster virus
(HZV) rates than the general population [6-8].
The
immune deterioration
associated with progression of herpes zoster infection may mimic
the aging process [9] and may explain the increased zoster incidence
noted in the HIV population.
Previous
studies have suggested that HIV patients manifest uniquely dramatic
and protracted herpes zoster infections compared with those who
are not immune compromised [10]. HIV patients tend to have recurrent
zoster episodes, multidermatomal involvement, and even systemic
disease.
Before
HAART, the incidence of post-herpetic neuralgia (PHN) in HIV patients
was the same compared with the general population but was remarkable,
considering the much younger age of the patients. [11] Other complications
such as ocular involvement, bacterial superinfection, myelitis,
meningitis, and chronic atypical skin lesions have also been reported
to be higher in patients with advanced HIV disease. [11]
Since
HAART became the standard of care in 1996, many changes have been
observed in the HIV epidemic that may be expected to have an impact
on the incidence of herpes zoster in this population. Patients with
HIV are living longer and may be more susceptible to developing
zoster through the aging process.
The
impact of HAART on the incidence of herpes zoster in HIV patients
is not fully understood. There are few reliable estimates of the
current incidence of zoster in the HAART era, although a recent
study in HIV-positive women
demonstrated an increased risk of herpes zoster in women with decreasing
CD4 counts.
[6]
In
the retrospective study conducted by the Johns Hopkins team, patients
with an episode of herpes zoster during this period were identified,
and their charts were reviewed.
Results
 |
Two
hundred eighty-two episodes of herpes zoster were identified
in 239 patients. |
|
Of
these episodes, 158 were new occurrences of zoster and 124 were
recurrent zoster events. |
|
The
incidence of zoster during the study period was 3.2 per 100
person-years of follow-up. |
|
The
incident cases reflected the clinic population, with most patients
being male (63%) and African
American (77%) and having injection
drug use as their HIV risk factor (49%). |
|
The
mean age of the patients was 41 years. |
|
Sixty-seven
percent of patients had single dermatomal involvement, and the
thorax was involved in 41%. |
|
In
multivariate regression, being on HAART and a CD4 count of 50
to 200 cells/mm3 compared with a CD4 count less than 50 cells/mm3
were associated with an increased risk of zoster. |
|
Twenty-eight
patients (18%) developed post-herpetic neuralgia (PHN), and
29 patients (18%) had other complications. |
|
Male-to-male
sex as an HIV risk factor (P = 0.02) and being on HAART at a
zoster episode (P = 0.03) were protective against complicated
zoster. |
Discussion
This
study has several important findings. First, the incidence rate
of herpes zoster among the Johns Hopkins urban cohort of HIV patients,
3.2 per 100 PYs of follow-up, is unchanged from the pre-HAART era
[11] and is nearly 10 times the incidence of 3.4 per 1000 PYs reported
by Hope-Simpson [5] in the general population.
Also,
patients on HAART and those with CD4 counts between 50 and 200 cells/mm3
seemed to be at the highest risk of a herpes zoster event. Finally,
the complication rate among incident cases, particularly of PHN,
was markedly higher than would be expected in an HIV-negative population
of similar age.
A
broad spectrum of zoster-associated complications was seen in this
population. The 60-day risk of complicated zoster in this HIV population
was 32.3%, which is more than double the 60-day risk of complicated
zoster found in general population studies, where estimates range
between 11% and 13%, [2,12] and contrasts with that of HIV patients
in the pre-HAART era (risk of 40%). [11] This is consistent with
the hypothesis that HIV patients are more vulnerable to developing
complications from herpes zoster than the general population.
Neurologic
complications were common in this study, affecting 27% of all patients.
PHN was the most common, occurring in 28 (18%) of patients, whereas
7 patients (4%) had aseptic meningitis, transverse myelitis, trigeminal
neuralgia, or Ramsay-Hunt syndrome, which is remarkably high compared
with that in the general population. [14] The rate of PHN is consistent
with the pre-HAART era.[11]
The
results are consistent with prior studies showing the probability
that an HIV-infected patient will have a recurrent zoster episode
within 1 year of the initial event is estimated at 12%. [15] Rates
of zoster recurrence in HIV patients are high when compared with
the general population, where estimates range between 1% and 4%.
[16]
In
contrast to previous work, there was no association between advanced
age [12] or lower CD4 cell counts [11] and complicated zoster. Recent
start of HAART was not associated with complicated zoster; however,
a lower viral load and being on HAART at zoster onset were protective
of complicated zoster.
These
results suggest that patients who are achieving virologic suppression on HAART
may be less likely to develop other complications because their
immune system is more able to control the zoster outbreak.
Patients
with men having
sex with men (MSM) as an HIV risk factor were less
likely to develop complicated zoster than those with other HIV risk
factors. One possible explanation for these results is that MSM
accessed the health care system for their herpes zoster infection
and began treatment more quickly.
Conclusions
The
Johns Hopkins study has several important implications. The incidence
of herpes zoster is unchanged from the pre-HAART era. Although the
zoster complication rate remains high, antiviral agents were frequently
used to treat zoster reactivation, suggesting that herpes zoster
has considerable morbidity despite appropriate treatment in HIV
patients.
Treatment
guidelines for PHN were developed for the immunocompetent patient
older than 50 years of age, and current management of herpes zoster
in HIV patients is based on extrapolation of these results. More
aggressive HIV patient-specific treatment guidelines, which recognize
that complications occur at a much higher rate and among a much
younger HIV population, may be necessary to prevent the important
complications of herpes zoster.
In
conclusion, the authors write, “Our results suggest that zoster
infection rates have not changed in the current HAART era but that
a significant percentage of patients develop complications, particularly
PHN, which is quite remarkable considering the young age of our
population.”
Department of Medicine, Johns Hopkins University School
of Medicine, Baltimore, MD; and Department of Neurology, Johns Hopkins
University School of Medicine, Baltimore, MD.
09/30/05
References
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K A Gebo and others.
The Incidence of, Risk Factors for, and Sequelae of Herpes Zoster Among
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1, 2005.
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