Acute cytomegalovirus infection in Kenyan HIV-infected infants

Abstract

Objective: Cytomegalovirus (CMV) coinfection may influence HIV-1 disease progression during infancy. Our aim was to describe the incidence of CMV infection and the kinetics of viral replication in Kenyan HIV-infected and HIV-exposed uninfected infants.

Methods: HIV-1 and CMV plasma viral loads were serially measured in 20 HIV-exposed uninfected and 44 HIV-infected infants born to HIV-infected mothers. HIV-infected children were studied for the first 2 years of life, and HIV-exposed uninfected infants were studied for 1 year.

Results: CMV DNA was detected frequently during the first months of life; by 3 months of age, CMV DNA was detected in 90% of HIV-exposed uninfected infants and 93% of infants who had acquired HIV-1 in utero. CMV viral loads were highest in the 1-3 months following the first detection of virus and declined rapidly thereafter. CMV peak viral loads were significantly higher in the HIV-infected infants compared with the HIV-exposed uninfected infants (mean 3.2 versus 2.7 log10 CMV DNA copies/ml, respectively, P = 0.03). The detection of CMV DNA persisted to 7-9 months post-CMV infection in both the HIV-exposed uninfected (8/17, 47%) and HIV-infected (13/18, 72%, P = 0.2) children. Among HIV-infected children, CMV DNA was detected in three of the seven (43%) surviving infants tested between 19 and 21 months post-CMV infection. Finally, a strong correlation was found between peak CMV and HIV-1 viral loads (rho = 0.40, P = 0.008).

Conclusion: Acute CMV coinfection is common in HIV-infected Kenyan infants. HIV-1 infection was associated with impaired containment of CMV replication.

Fig. 1. The kinetics of cytomegalovirus viral load during acute infection in HIV-exposed infants

Infants are grouped by mode of HIV-1 acquisition (rows) and timing of first CMV detection (columns). Individual infants are represented by gray lines, when a sufficient number of cases were present to fit a model a median spline was added (black line). In the infants with late HIV-1 acquisition, the time of first HIV-1 detection for each infant is indicated by the point labelled ‘HIV’. n, the number of infants in each group. ^aIncludes one infant with first CMV detection at 2 months. CMV, cytomegalovirus.

Fig. 2. HIV-1 infection and cytomegalovirus replication

(a) Mean peak CMV viral loads are shown for HIV-infected and HIV-exposed uninfected infants. Excludes infants who acquired HIV-1 after 1 month of age. Middle lines show group means and whiskers show standard error of the mean. (b) CMV viral loads are shown for HIV-infected and HIV-exposed uninfected infants. To control for age, differential timing of HIV/CMV infection and mortality, data are restricted to infants who were first CMV positive at 3 months of age and survived 12 months of follow-up. Infants with late HIV-1 acquisition were excluded from this figure. Solid line and solid circles show 15 infants with HIV-1, dashed line and open circles show 14 HIV-1-uninfected infants. Circles show individual infant measurements and lines show fitted median splines. (c) Scatter plot shows peak CMV and HIV-1 viral loads and linear regression line. CMV, cytomegalovirus.