Ongoing burden of disease and mortality from HIV/CMV coinfection in Africa in the antiretroviral therapy era.

Emily Adland,Philip Goulder,Paul Klenerman,Philippa C Matthews

doi:10.3389/fmicb.2015.01016

Abstract

Human Cytomegalovirus (CMV) is a well-recognized pathogen in the context of HIV infection, but since the roll out of ART, clinical and scientific interest in the problem of HIV/CMV coinfection has diminished. However, CMV remains a significant cofactor in HIV disease, with an influence on HIV acquisition, disease progression, morbidity, and mortality. Disease manifestations may be a result of direct interplay between the two viruses, or may arise as a secondary consequence of immune dysregulation and systemic inflammation. The problem is most relevant when the rates of coinfection are high, most notably in sub-Saharan Africa, and in children at risk of acquiring both infections early in life. Understanding the interplay between these viruses and developing strategies to diagnose, treat and prevent CMV should be a priority.

Highlights

Human cytomegalovirus (CMV) is a ubiquitous β-herpesvirus, known as Human Herpes Virus 5 (HHV5)
The complex interplay between these two chronic viral infections continues to be potentially highly significant, both in adults and children, and in certain vulnerable populations, including subSaharan Africa, where both CMV and Human Immunodeficiency Virus (HIV) are endemic in neonates and children, leading to a risk of coinfection in utero and during the earliest days of life (King et al, 2013)
There is increasing evidence to suggest that CMV remains a relevant co-factor in disease progression in individuals with HIV, irrespective of Antiretroviral Therapy (ART) (Riou et al, 2015), highlighted by the following three points: Accelerated Rate of Progression of HIV Progression to an AIDS-defining event has been significantly and independently associated with HIV RNA viral load and CD4+ T cell count, and with CMV DNA (Erice et al, 2003; Fielding et al, 2011)

Summary

Introduction

Human cytomegalovirus (CMV) is a ubiquitous β-herpesvirus, known as Human Herpes Virus 5 (HHV5). Similar observations were made in HEU infants (Slyker et al, 2012) These data support the hypothesis that CMV-induced T cell activation and Fas-mediated apoptosis potentially contribute to the increased HIV disease progression observed in CMV coinfected infants (Kovacs et al, 1999). There is increasing evidence to suggest that CMV remains a relevant co-factor in disease progression in individuals with HIV, irrespective of ART (Riou et al, 2015), highlighted by the following three points: Accelerated Rate of Progression of HIV Progression to an AIDS-defining event has been significantly and independently associated with HIV RNA viral load and CD4+ T cell count, and with CMV DNA (Erice et al, 2003; Fielding et al, 2011). A recent study of HIV-positive adults in rural Tanzania that used dried blood spots to detect CMV viraemia found a hazard ratio of 5 for mortality in the presence of CMV (Brantsæter et al, 2012)

Population Findings

25 HIV-positive children with suspected PJP

Conclusions