Congenital and postnatal CMV and EBV acquisition in HIV-infected Zimbabwean infants.

Hlanai Gumbo,Bernard Chasekwa,Kuda Mutasa,Robert Ntozini,James A Church,Jean H Humphrey,Andrew J Prendergast,Soren Gantt

doi:10.1371/journal.pone.0114870

Abstract

BackgroundHIV-infected infants in sub-Saharan Africa have rapid disease progression. We hypothesized that co-infection with cytomegalovirus (CMV) or Epstein Barr virus (EBV) increases mortality in HIV-infected infants.Methods257 antiretroviral therapy-naïve HIV-infected Zimbabwean infants were tested for CMV and EBV at 6 weeks of age by real-time PCR; if positive, birth samples were retrieved where available to distinguish congenital and postnatal infection. The impact of co-infection on mortality through 6 months was estimated using Kaplan-Meier and Cox proportional hazards methods.ResultsAt 6 weeks, 203/257 (79%) HIV-infected infants were CMV-positive; 27 (11%) had congenital CMV, 108 (42%) postnatal CMV and 68 (26%) indeterminate timing of infection. By 6 months, 37/108 (34%) infants with postnatal CMV versus 16/54 (30%) CMV-negative infants died (adjusted hazard ratio (aHR) 1.1 [95%CI 0.6, 2.2]). At 6 weeks, 33/257 (13%) HIV-infected infants had EBV co-infection; 6 (2%) had congenital EBV, 18 (7%) postnatal EBV and 9 (4%) indeterminate timing of infection. By 6 months, 5/18 (28%) infants with postnatal EBV versus 72/224 (32%) EBV-negative infants died (aHR 0.8 [95%CI 0.3, 2.3]).ConclusionsThe vast majority of HIV-infants had acquired CMV by 6 weeks, and EBV co-infection occurred earlier than expected, with one in eight HIV-infected infants positive for EBV by 6 weeks. There was a high prevalence of congenital CMV infection and we identified 6 infants with congenital EBV infection, which has not previously been reported in Africa or in the context of HIV infection. Neither CMV nor EBV co-infection was associated with increased mortality.

Highlights

Despite scale-up of prevention of mother-to-child transmission (PMTCT) interventions, approximately 700 HIV-infected infants are born daily, predominantly in sub-Saharan Africa [1]
There was a high prevalence of congenital CMV infection and we identified 6 infants with congenital Epstein Barr virus (EBV) infection, which has not previously been reported in Africa or in the context of HIV infection
Because infants were selected at 6 weeks of age for inclusion in this study, we were not able to investigate the impact of congenital CMV or EBV infection on survival

Summary

Introduction

Despite scale-up of prevention of mother-to-child transmission (PMTCT) interventions, approximately 700 HIV-infected infants are born daily, predominantly in sub-Saharan Africa [1]. Co-infection with other viruses, such as cytomegalovirus (CMV) and Epstein Barr virus (EBV), has been hypothesized to influence HIV disease progression [7, 8, 9]. In a US study of 52 HIV-infected infants, disease progression was more rapid in infants co-infected with CMV compared to those infected with HIV alone [8]. No studies to date have investigated whether CMV influences HIV disease progression in sub-Saharan Africa, where CMV is acquired earlier and HIV disease course is more rapid than in USA/Europe. HIV-infected infants in sub-Saharan Africa have rapid disease progression. Methods: 257 antiretroviral therapy-naıve HIV-infected Zimbabwean infants were tested for CMV and EBV at 6 weeks of age by real-time PCR; if positive, birth samples were retrieved where available to distinguish congenital and postnatal infection. Neither CMV nor EBV co-infection was associated with increased mortality

Methods

Results

Conclusion