Significant levels of cytomegalovirus (CMV) DNA are common in older African children with perinatally acquired HIV infection, even in children treated with antiretroviral therapy (ART), according to results of a study published in Clinical Infectious Diseases. These findings suggested that the pathogenesis of perinatally acquired HIV infection comorbidities are influenced by an inappropriate control of the CMV infection.
In this study, the researchers hypothesized that infants with perinatally acquired HIV infection who had not been treated with ART, and who later acquired CMV coinfection may fail to establish adequate immune CMV control. Researchers also postulated that this may lead to future episodes of CMV reactivation or replication that in turn drives some of the comorbidities described in survivors of perinatally acquired HIV. To this end, the study investigators examined the associations between CMV DNA and lung function and growth.
The study investigators evaluated 626 participants from 2 prospective cohorts: the ZENITH cohort, which recruited children between the ages of 6 years and 16 years who were newly diagnosed with HIV, and the INHALE cohort, which recruited children between the ages of 6 years and 16 years who had been taking ART for >6 months. Children who tested negative for HIV in the same age group joined the study as population controls and provided a single blood sample without further follow-up. Plasma CMV DNA loads were measured in children with perinatally acquired HIV (n=402) and controls without HIV (n=224). CMV DNA loads were measured using quantitative polymerase chain reaction. The highest forced expiratory volume in the first second and forced vital capacity were measured with spirometry. Height was recorded at baseline for all the participants. For the multivariate analysis of time-varying outcomes, the study investigators used longitudinal mixed-methods logistic regression.
During enrollment of the study, CMV DNA ≥1000 copies/mL, which has been established as clinically significant, was detected in 5.8% of children without HIV, 14.7% of participants with HIV who were stable on ART, and 22.6% of children with HIV who had never received treatment with ART (χ²=23.8; P <.001). The prevalence of CMV DNA ≥1000 copies/mL was associated with CD4 counts <350 cells/μL. In children with HIV who had never received treatment with ART, the presence of CMV DNA ≥1000 copies/mL was independently associated with reduced lung function (adjusted odds ratio [aOR] 3.23; 95% CI, 1.23-8.46; P =.017). In children who had received treatment with ART, growth stunting was associated with CMV DNA of ≥1000 copies/mL (aOR 2.79; 95% CI, 0.97-8.02; P =.057). Growth stunting and reduced lung function were not associated with CMV viral load.
Some of the limitations noted by the study investigators are the lack of information about HIV RNA in the participants who had never received ART at enrollment. The INHALE participants may have elevated HIV RNA as a result of poor adherence. In addition, the data do not allow determination of the direction of associations; therefore, the study investigators could not conclude that CMV is a cause of growth stunting.
This investigation opens new questions and calls for more studies to further analyze the “potential role of CMV reactivation in the pathogenesis of the serious complications of [perinatally acquired HIV infection] in Africa and to determine whether or not specific antiviral drugs such as valganciclovir might be helpful in these conditions.”
Yindom LM, Simms V, Majonga ED, et al. Unexpectedly high prevalence of cytomegalovirus DNAemia in older children and adolescents with perinatally acquired human immunodeficiency virus infection [published online March 4, 2019]. Clin Infect Dis. doi: 10.1093/cid/ciy961