Incidence of Herpes Zoster in HIV-Infected Patients Undergoing Antiretroviral Therapy: A Systematic Review and Meta-analysis

Abstract

The incidence of herpes zoster (HZ) in patients infected with HIV is higher than that of the general population. However, the incidence of HZ in HIV patients receiving antiretroviral therapy (ART) remains unclear. This meta-analysis aimed to estimate the pooled incidence rate and risk factors for HZ in the post-ART era. We identified studies assessing the incidence of HZ in the post-ART era between 1 January 2000 and 28 February 2021, from four databases. Pooled risk ratios were calculated from 11 articles using a random-effects model. The heterogeneity of the included trials was evaluated by visually inspecting funnel plots, performing random-effects meta-regression and using I² statistics. Of the 2111 studies screened, we identified 11 studies that were eligible for final inclusion in the systematic review and 8 studies that were eligible for a meta-analysis. The pooled incidence of HZ in the post-ART era (after the introduction of ART in 1997) was 2.30 (95% confidence interval (CI): 1.56-3.05) per 100 person years (PYs). The risks of incidence of HZ among people living with HIV included male sex (AOR: 4.35 (95% CI: 054-2.41)), men who have sex with men (AOR: 1.21 (95% CI: -0.76-1.13)), CD4 count < 200 cells/μL (AOR: 11.59 (95% CI: 0.53-4.38)) and not receiving ART (AOR: 2.89 (95% CI: -0.44-2.56)). The incidence of HZ is substantially lower among HIV infected patients receiving ART than those not receiving ART. Initiating ART immediately after diagnosis to treat all HIV-positive individuals is crucial to minimize the disease burden of HZ.

Keywords: HIV-infected patients; herpes zoster; highly active antiretroviral therapy; incidence; meta-analysis.

Figure 1

Preferred reporting items for systematic review and meta-analyses (PRISMA) flow diagram for searching and identifying included studies. Database: PubMed (n = 221), Embase (n = 1793), Cochrane Library (n = 23) and CINAHL (n = 74). Keywords: (Human Immunodeficiency Virus OR Acquired Immune Deficiency Syndrome Virus* OR Lymphadenopathy-Associated Virus*) AND (HAART OR ART OR Antiretroviral Therapy*) AND (Incidence OR Herpes Zoster OR Varicella Zoster Virus* OR herpes virus infection). Date: available until 28 February 2021.

Figure 2

Meta-analyses of (a) HZ incidence of HIV-infected patients among ART-era therapy, (b) subgroup segmented by sex, (c) subgroup segmented by CD4 count level and (d) subgroup segmented by ART use. (Note: in the graph, the square represents the effect size of each study. The bigger the square, the more participants in the study. A horizontal line represents the 95% confidence intervals of the study result, with each end of the line representing the boundaries of the confidence interval. The diamond represents the combined effect. Pre-ART = not receiving ART. Post-ART = receiving ART).

Figure 2

Meta-analyses of (a) HZ incidence of HIV-infected patients among ART-era therapy, (b) subgroup segmented by sex, (c) subgroup segmented by CD4 count level and (d) subgroup segmented by ART use. (Note: in the graph, the square represents the effect size of each study. The bigger the square, the more participants in the study. A horizontal line represents the 95% confidence intervals of the study result, with each end of the line representing the boundaries of the confidence interval. The diamond represents the combined effect. Pre-ART = not receiving ART. Post-ART = receiving ART).

Figure 3

Funnel plots of HZ incidence. (Note: in the graph, the observed studies are shown as open circles and the observed point estimate in log units us shown as a diamond).