Unexpectedly High Prevalence of Cytomegalovirus DNAemia in Older Children and Adolescents With Perinatally Acquired Human Immunodeficiency Virus Infection.

Louis-Marie Yindom,Edith D Majonga,Victoria Simms,Helene Vincon,Tsitsi Bandason,Jamie Rylance,Grace Mchugh,Shungu Munyati,Rashida A Ferrand,Sarah L Rowland-Jones,Ethel Dauya

doi:10.1093/cid/ciy961

Abstract

BackgroundOlder children and adolescents with perinatally acquired human immunodeficiency virus (PHIV) infection in Africa experience multiple comorbidities that are not typical of HIV-associated opportunistic infections, including growth impairment and chronic lung disease. We examined associations between plasma cytomegalovirus (CMV) DNA and lung function and growth.MethodsPlasma CMV DNA loads were measured children aged 6–16 years with PHIV (n = 402) and HIV-uninfected controls (n = 224). The HIV-infected children were either newly diagnosed or known HIV infected and stable on antiretroviral therapy (ART) for >6 months. CMV DNA loads were measured using quantitative polymerase chain reaction. CMV DNAemia was modeled as a time-varying outcome using longitudinal mixed-effects logistic regression.ResultsAt enrollment, CMV DNAemia ≥1000 copies/mL (defined as “clinically significant”) was detected in 5.8% of uninfected children, 14.7% of HIV-infected participants stable on ART, and 22.6% of HIV-infected ART-naive children (χ2 = 23.8, P < .001). The prevalence of CMV DNAemia ≥1000 copies/mL was associated with CD4 counts <350 cells/µL. Among HIV-infected ART-naive children, the presence of CMV DNAemia of ≥1000 copies/mL was independently associated with reduced lung function (adjusted odds ratio [aOR] = 3.23; 95% confidence interval [CI], 1.23–8.46; P = .017). Among ART-treated children, stunting was associated with CMV DNAemia of ≥1000 copies/mL (aOR = 2.79; 95% CI, 0.97–8.02; P = .057).ConclusionsClinically significant levels of CMV DNAemia were common in older children with PHIV, even those on ART, suggesting a role for inadequately controlled CMV infection in the pathogenesis of PHIV comorbidities in Africa.

Highlights

Older children and adolescents with perinatally acquired human immunodeficiency virus (PHIV) infection in Africa experience multiple comorbidities that are not typical of HIV-associated opportunistic infections, including growth impairment and chronic lung disease
Before the widespread availability of antiretroviral therapy (ART), pediatric human immunodeficiency virus (HIV) in Africa was characterized by rapid disease progression, with
It is thought that one third of children with PHIV progress more slowly and can survive into their teens, even without ART [2]

Summary

Methods

Plasma CMV DNA loads were measured in children aged 6–16 years with PHIV (n = 402) and HIV-uninfected controls (n = 224). The HIV-infected children were either newly diagnosed or known HIV infected and stable on antiretroviral therapy (ART) for >6 months. The ZENITH cohort recruited children aged 6–16 years who were newly diagnosed with HIV following provider-initiated HIV testing in primary healthcare clinics in Harare, Zimbabwe [15]. The INHALE cohort recruited children in the same age group who had been taking ART for >6 months from an HIV clinic at Harare Children’s Hospital, which served the same catchment population as the primary healthcare clinics. Height was recorded at baseline for all participants, and HIV-infected participants were followed for 18 months, with clinical and laboratory examinations every 3 months.

Results

Discussion

Conclusion