Herpes zoster (HZ), also known as shingles, is caused by the reactivation of varicella zoster virus (VZV), which remains latent in the sensory ganglia following varicella infection [1]. HZ is a human immunodeficiency virus (HIV)-associated opportunistic infection. HIV infected populations have a 3- to 20-fold higher risk of contracting HZ than HIV seronegative individuals ^{[2][3][4][5][6]}[2,3,4,5,6]. A systematic review and meta-analysis of the HZ incidence in ART-naive patients was 9.4%. During the first year of ART, the incidence was 2.3%, but this reduction was not statistically significant [7].

Even though the introduction of ART has improved the survival of those living with HIV, the incidence of HZ among HIV cohorts remains higher than that of the general population ^[4][8][4,8]. The incidence of HZ in the HIV cohort was 9.3–141 per 1000 patient years (PY)s ^[8][9][10][8,9,10]; but the incidence of HZ in the general population is only 3–5 per 1000 PYs [11]. The general population lifetime risk for HZ is between 23.8% and 30% and affects approximately one in four people in Europe; however, for those aged >85 years, the risk increases to one in two people [12].

ART was previously associated with reduced risk of herpes zoster and other opportunistic infections and could substantially improve the quality of life among HIV infected patients [7]. The long-term effects of ART on HZ incidence among HIV infected cohorts have been inconsistent across previous studies. A study in 2005 noted that the HZ incidence has not significantly decreased since the advent of ART [9]. Conversely, other prior studies found a reduction in the risk of HZ after the initiation of ART in North America, Europe, Taiwan and Africa ^{[4][8][10][13][14][15][16][17]}[4,8,10,13,14,15,16,17]. Several studies have shown an increase in the HZ incidence during the first to fourth months following ART therapy, which suggests that HZ may be a feature of immune reconstitution inflammatory syndrome (IRIS) ^[9][18][19][9,18,19].

A better understanding of the risk factors for HZ for the HIV infected population may provide valuable information for health care professionals to identify adult patients at a heightened risk and could help formulate appropriate policies for vaccination strategies for the HIV-infected population [20]. Therefore, the objective of meta-analysis aimed to systematically review studies estimating the incidence and risk factors for HZ in the post-ART era among people living with HIV (PLWH) and discuss implications based on the updated evidence.

2. Results

23.1. Study Characteristics

During the period from 1 January 2000 to 28 February 2021, we identified 2111 records: 221 from PubMed, 1793 from Embase, 23 from Cochrane Library and 74 from CINAHL. After removing duplications and the initial screening, 45 articles were eligible for full-text review (Figure 1). Eleven studies met the inclusion criteria for the meta-analysis. The 11 studies received a quality score of ≥8, with nine studies receiving a score of >10 out of 12 (Table 1). The 11 studies included 10 cohort studies and 1 clinical observational study. Overall, the study quality was acceptable. These 11 studies included 195,190 total HIV infected participants. The incidence was reported for populations in America (four studies), Europe (four studies), Asia (one study) and Africa (two studies). The pooled incidence rate of HZ in the 11 studies was 2.30 (95% CI: 1.56–3.05) per 100 person years (PYs) (Figure 2a). Due to high heterogeneity, subgroup analyses were conducted and stratified by gender, income, AIDS history, study observational years, HIV risk factors and CD4 cell count (Table 2). Among the 10 studies, patients with high income (pooled RR, 2.64; 95% CI, 1.62–3.65) had the pooled HZ incidence greater than those with low income (pooled RR, 1.33; 95% CI, −0.56–3.22). Among the 4 studies, patients without AIDS history (pooled RR, 0.60; 95% CI, 0.46–0.72) had the pooled HZ incidence greater than those who had AIDS history (pooled RR, 0.40; 95% CI, 0.28–0.54). Among the 4 studies, patients being heterosexual had the pooled HZ incidence (pooled RR, 0.41; 95% CI, 0.31–0.52) greater than IDUs and MSM. Of the 4 studies, patients with a CD4 count < 200 cells/mm³ (pooled RR, 0.78; 95% CI, 0.55–0.91) were at increased risk of HZ compared with those with a CD4 count > 200 cells/mm³ (pooled RR, 0.21; 95% CI, 0.06–0.51).