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

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.

Keywords: CMV; HIV-1; antiretroviral therapy; coinfection; immune activation; pediatric infectious diseases; sub-Saharan Africa.

Figure 1

Worldwide CMV seroprevalence rates in adults. We have represented studies of adults aged 16–50 years published between 2005 and 2015 from Australia, Belgium, Brazil, Canada, Cambodia, Chile, China, Finland, France, Gambia, Germany, Ghana, India, Israel, Italy, Japan, Kenya, Mexico, Nigeria, Panama, South Africa, Spain, Sweden, Taiwan, Tanzania, Turkey, UK, USA, Zambia, and Zimbabwe (Chakraborty et al., ; Schlesinger et al., ; Miles et al., , ; van der Sande et al., ; Zhang et al., ; Dar et al., ; Alao et al., ; Compston et al., ; Micol et al., ; Pass et al., ; Cannon et al., ; Chakravarti et al., ; Fielding et al., ; Brantsæter et al., ; Hsiao et al., ; Manicklal et al., , ; Gumbo et al., ; Lanzieri et al., ; Mwaanza et al., ; Schaftenaar et al., ; Lichtner et al., ; Tembo et al., ; Viljoen et al., 2015).

Figure 2

Impact of the immune system on CMV. CMV immune control is reliant on both the innate and adaptive arms of the immune system. We have here summarized the key elements, highlighting the complex interplay of multiple limbs of the immune system in containing CMV infection.

Figure 3

Impact of CMV on the immune system. This figure shows the potential for bi-directional interplay between CMV and the immune response. CMV induces a robust humoral and cellular immune response whilst at the same time has a direct influence on normal immune function. Factors such as poor nutrition and low weight, crowded living conditions and other herpes virus coinfections also have an impact on immune function and are associated with increased CMV seroprevalence.