Background:  Herpes zoster (HZ) is a common, painful complication in HIV-infected children. Little is known regarding the impact of potential risk factors on HZ among HIV-infected youth. We hypothesize that incidence of HZ has declined over time, as a result of direct and indirect effects of HAART and the varicella zoster virus (VZV) vaccine.

Methods: The study included 811 perinatally HIV-infected children enrolled in PACTG 219/219C with a history of VZV. Participants were considered to be at risk of HZ 30 days after a diagnosis of VZV or HZ, until their last study visit date prior to July 1, 2004. Incidence rates, 95% confidence intervals (CI), and 2-sided p-values were calculated under a Poisson distribution. Cox regression models were used to evaluate associations of potential predictors with HZ.

Results:  There were 422 incident cases of HZ over 3943 person-years of follow-up (incidence rate 10.7/100 person-years; 95%CI 9.7 to 11.8). Incidence declined over time (p <0.01), with a maximum incidence rate of 21.5 (16.7 to 27.2) in 1996 and a minimum incidence rate of 5.9 (3.4 to 9.5) in 2003. There were 172 recurrent cases (n = 108) over 2230 person-years (7.7/100 person-years, 6.6 to 9.0), with a similar decline by year (p <0.01). Incidence rates significantly declined with increasing CD4% (<15% vs ≥25%: 28.6, 23.7 to 34.2 vs 4.8, 3.8 to 6.0), decreasing viral load (>100,000 vs ≤400 viral RNA copies/mL: 17.7, 12.6 to 24.2 vs 3.9, 2.4 to 5.8), and HAART (HAART vs non-HAART: 8.4, 7.1 to 10.0 vs 12.2, 10.9 to 13.7). A protective effect of VZV vaccination (post-VZV infection, in most cases) was suggested (vaccine vs no vaccine: 7.8, 4.1 to 13.3 vs 10.8, 9.8 to 11.9), but there were only 65 vaccine recipients (167 person-years). Race/ethnicity and gender were not associated with incident HZ. A multivariate Cox model for time to HZ indicated a non-significant protective effect of HAART (hazard ratio, time-dependent HAART vs non-HAART:  0.82, 0.63 to 1.07, p = 0.14), after adjustment for age and year at VZV, nadir CD4%, maximum RNA, and VZV vaccination. Nadir CD4% (<15% vs ≥25%; 3.51, 2.39 to 5.16; p <0.01) was a significant predictor of HZ in this model.

Conclusions:  Incidence and recurrence rates of HZ in HIV-infected children and adolescents have declined over time yet remain substantial. CD4% is a significant independent predictor of HZ. Our results suggest that HAART is protective against HZ, but the effect of VZV vaccination could not be adequately assessed in our study.