To the Editors:
Herpes zoster, the reactivation of latent varicella zoster virus infection, is common among individuals with immunocompromised conditions such as malignancies, chronic steroid use, and HIV infection.1 The risk for herpes zoster, in HIV-infected patients, is 10 to 20 times higher than among healthy middle-aged adults.2,3 Contrary to other opportunistic infections, zoster occurs at a wide range of CD4 T-cell counts in HIV-infected patients.4 In some individuals, it can be the first clue to the diagnosis of HIV infection, whereas recurrent episodes of zoster may represent a progression of HIV infection in others.4,5 Zoster in HIV-infected patients is likely to be more severe and complicated compared with the general population with findings such as recurrent zoster episodes, involvement of multidermatome, systemic diseases, and neurologic complications, including postherpetic neuralgia.6 Moreover, HIV-infected persons who develop zoster are also at high risk for the progression to AIDS and death.7,8 Highly active antiretroviral therapy (HAART) might affect the clinical course of zoster, which would be diverse in relation with CD4 cell count, age, race, and comorbidities.
In this study, we evaluated the clinical features and risk factors for complications of herpes zoster among HIV-infected zoster patients compared with non-HIV-infected patients in South Korea in the era of HAART. The Korean HIV/AIDS HAART cohort is composed of five university hospitals, which was organized and began operations in October 2006. We conducted a retrospective cohort study of HIV-infected patients between January 1, 2001, and December 31, 2007. Patients with an episode of herpes zoster during this period were identified, and their medical records were reviewed. The CD4 T-cell count and HIV-1 RNA load were recorded serially: within recent 3 months before the onset of zoster, at the time of the onset of zoster (± 2 weeks) and 6 to 12 months later after the onset of zoster. The clinical features of the HIV-infected zoster patients were analyzed based on their immune status and compared with zoster patients who were not HIV-infected (controls). The retrospective controls were selected during the same calendar month that zoster occurred in the HIV-infected patients (frequency-matched controls); controls were also tested for HIV infection.
The immune reconstitution syndrome (IRS) was defined as worsening symptoms of herpes zoster without newly acquired infection/inflammatory condition, increase in the CD4 T-cell count 50 cells/mm3 or greater, and adequate virologic response (1 log10 or more decrease in viral load) while on antiretroviral therapy compared with a recent 3- to 6-month nadir before the onset of herpes zoster.9,10 Zoster-related complications included ocular, visceral, or neurologic problems compatible with the diagnosis of herpes zoster without any other definite causes. Postherpetic neuralgia was defined as continuing pain (burning, throbbing, or stabbing) even 4 weeks after the complete resolution of cutaneous disease associated with herpes zoster.11
A total of 55 (14.7%) among the 374 HIV-infected patients had herpes zoster during the study period. The medical records of 40 cases were available, and they were compared with 60 zoster cases that were not infected with HIV. The HIV-infected zoster patients were younger (42.9 ± 10.2 years versus 59.4 ± 13.8 years, P < 0.01) and rarely had comorbid conditions (aside from HIV infection) compared with the patients without HIV (7.5% versus 35%, P < 0.01). Male gender was more common in HIV-infected zoster patients compared with the HIV-uninfected zoster patients (90% versus 38.3%, P < 0.01). There was no significant clinical difference between the two groups with regard to the number and location of involved dermatomes, duration of persistent skin lesions, complications, and recurrence. The mean interval between HIV identification and occurrence of zoster was 39.7 ± 42.3 months. Among 40 HIV-infected zoster patients, 30 (75%) were on HAART. Mean CD4 T-cell counts and HIV-1 RNA loads were 228.0 ± 197.0 cells/mm3 and 3.59 ± 1.50 log10 copies/mL, respectively.
As for zoster-related complications, there was no significant difference in age, gender, comorbidity, and HAART regimens/duration between complicated and uncomplicated zoster in the HIV-infected patients (Table 1). On univariate analysis, the zoster-related complication rate was not affected by either the CD4 lymphocyte count or the HIV-1 RNA load. However, the complication rate was significantly increased with the IRS (P = 0.037); nine of 12 cases manifested the IRS. Intravenous acyclovir was more commonly used in patients with zoster-related complications. On multivariate analysis, no statistically significant risk factor was identified for zoster-related complications.
In this retrospective cohort study, we found several important characteristics of zoster in HIV-infected patients. First, zoster occurred at a younger age in the HIV-infected patients without underlying comorbidity compared with the zoster patients without HIV. Second, the clinical features and complication rates were similar between the HIV-infected and uninfected zoster patients. Third, the occurrence of complicated zoster was not correlated with the immunologic or virologic status of the HIV-infected patients, but it was closely related to the IRS. Previously, some studies suggested that zoster may be associated with the IRS resulting from hyperacute immune responses that occur soon after the initiation of HAART.4 In comparison, fewer than half of the zoster cases were associated with IRS in the present study. However, the risk of zoster-related complications was markedly increased in patients with the IRS after HAART initiation. Complicated zoster might accelerate AIDS progression, although some studies reported that zoster did not lead to faster disease progression.7,8
Of note, increased zoster susceptibility may occur at an intermediate level of CD4 T-cell counts, and complication rates are higher when zoster occurs as a manifestation of IRS, especially during the early HAART period. Although this study has the limitations of a retrospective design, the findings might have practical implications: prophylactic varicella zoster virus-specific antiviral therapy in a subset of at-risk patients (especially those with rapid increase of CD4 in the first month after HAART initiation), early varicella zoster virus-specific antiviral therapy as soon as the development of suspicious skin lesions, zoster vaccination at the time of HIV identification with preserved immunity, and so on.
Joon Young Song, MD, PhD*
Hee Jin Cheong, MD, PhD*
Woo Joo Kim, MD, PhD*
Jin Soo Lee, MD, PhD†
Moon Hyun Jung, MD, PhD†
Hye Won Jung, MD, PhD‡
Hee Jung Choi, MD, PhD§
Jin Seo Lee, MD∥
Joong Shik Eom, MD, PhD∥
*Division of Infectious Diseases
Department of Internal Medicine
Korea University College of Medicine
†Inha University College of Medicine
‡Chungbuk National University College of Medicine
§Ewha University College of Medicine
∥Hallym University College of Medicine
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