Herpes Zoster in Persons Living with HIV-1 Infection: Viremia and Immunological Defects Are Strong Risk Factors in the Era of Combination Antiretroviral Therapy

Abstract

In a cohort of 4,225 persons living with human immunodeficiency virus type 1 (HIV-1) infection (PLWH) enrolled at a southeastern US clinic, the overall rate of incident herpes zoster (HZ) was 101 per 10,000 person-years (PY) between January 1999 and 2017, which nearly quadruples the rate reported for the general US population. In the same cohort, the median age of HZ diagnosis was 39.5 years [interquartile range (IQR) 31.5-49.2] in African American (AA) and 39.1 years (IQR 34.9-45.2) in European American (EA) PLWH, with the highest incidence seen in PLWH who were over 50 years old (144 and 93 per 10,000 PY in AA and EA, respectively, P = 0.18), showing no bias between men (100 per 10,000 PY) and women (101 per 10,000 PY). In multivariable models that were applicable to 245 HZ cases and 3,713 controls, age, nadir CD4⁺ T-cell (CD4) count, plasma viral load (VL), and duration of combination antiretroviral therapy were independent correlates of incident HZ (adjusted P ≤ 0.006 for all). Regardless of other factors, viremic PLWH (VL > 50 copies/mL) was at the highest risk of HZ [adjusted odds ratio (OR) > 3.0, P < 0.0001]. PLWH with a nadir CD4 count of ≥500 cells/μL showed a relatively low risk (adjusted OR = 0.48, P = 0.003). By contrast, similar risk estimates were observed with three advancing age groups (30-39, 40-49, and ≥50) when compared with age <30 (adjusted OR = 1.86-2.17, P ≤ 0.010). These findings indicate that efforts for HZ diagnosis and prophylaxis should target viremic PLWH who are over 30 years old and with CD4 count <500 cells/μL.

Keywords: correlation; epidemiology; herpes zoster; human immunodeficiency virus type 1; incident rate.

Figure 1

A flow chart for the selection of 245 incident herpes zoster (HZ) cases and 3,713 control subjects for this study. A total of 4,225 subjects are included in initial analyses.

Figure 2

The age of onset for incident herpes zoster (HZ) cases as observed in African American (AA) and European American (EA) persons living with HIV-1 infection. The median age at HZ diagnosis is 39.5 years in AA and 39.1 years in EA (P > 0.50).

Figure 3

Incidence of herpes zoster (HZ) as observed between 2000 and 2016 in the study cohort. Solid line indicates the average HZ diagnoses (per 1,000 subjects) over time (in yearly intervals), while dotted lines correspond to the 95% confidence intervals.

Figure 4

Kaplan–Meier curves showing time from study enrollment (January 1999) to events of herpes zoster (HZ) in the study population (N = 4,225) stratified by sex (top panel) or race (bottom panel). No clear differences are seen between men and women or among three ethnic groups (AA, African American; EA, European American), being consistent with logistic regression models (Table 1).