Early postnatal cytomegalovirus infection may predict subsequent HIV transmission through breastfeeding

Effect of cytomegalovirus infection on breastfeeding transmission of HIV and on the health of infants born to HIV-infected mothers.

Chang TS, Wiener J, Dollard SC, Amin MM, Ellington S, Chasela C, Kayira D, Tegha G, Kamwendo D, Jamieson DJ, van der Horst C, Kourtis AP; BAN Study Team. AIDS. 2015 Apr 24;29(7):831-6. doi: 10.1097/QAD.0000000000000617

Background: Cytomegalovirus (CMV) infection can be acquired in utero or postnatally through horizontal transmission and breastfeeding. The effect of postnatal CMV infection on postnatal HIV transmission is unknown.

Methods: The Breastfeeding, Antiretrovirals and Nutrition study, conducted in Malawi, randomized 2369 mothers and their infants to three antiretroviral prophylaxis arms - mother (triple regimen), infant (nevirapine), or neither - for 28 weeks of breastfeeding, followed by weaning. Stored plasma and peripheral blood mononuclear cell specimens were available for 492 infants at 24 weeks and were tested with CMV PCR. Available samples from infants who were CMV PCR-positive at 24 weeks were also tested at birth (N = 242), and from infants PCR-negative at 24 weeks were tested at 48 weeks (N = 96). Cox proportional-hazards models were used to determine if CMV infection was associated with infant morbidity, mortality, or postnatal HIV acquisition.

Results: At 24 weeks of age, CMV DNA was detected in 345/492 infants (70.1%); the estimated congenital CMV infection rate was 2.3%, and the estimated rate of CMV infection at 48 weeks was 78.5%. CMV infection at 24 weeks was associated with subsequent HIV acquisition through breastfeeding or infant death between 24 and 48 weeks of age (hazard ratio 4.27, P = 0.05).

Conclusion: Most breastfed infants of HIV-infected mothers in this resource-limited setting are infected with CMV by 24 weeks of age. Early CMV infection may be a risk factor for subsequent infant HIV infection through breastfeeding, pointing to the need for comprehensive approaches in order to achieve elimination of breastfeeding transmission of HIV.

Abstract access  [1]

Editor’s notes: Studies have illustrated that mother-to-child HIV transmission is more frequent among neonates with congenital cytomegalovirus (CMV) infection. Infants co-infected with HIV and CMV have higher rates of HIV disease progression and death. This study using data and samples of infant plasma and peripheral blood mononuclear cells are from the Breastfeeding, Antiretrovirals and Nutrition (BAN) randomised, controlled clinical trial (RCT). The study examines whether postnatal CMV infection in the infant is associated with HIV transmission through breastfeeding. The study investigates the relationship between postnatal antiretroviral therapy and postnatal CMV acquisition. The data suggests that early postnatal CMV infection in an HIV-exposed uninfected infant may predict subsequent HIV transmission through breastfeeding and infant mortality. The study confirmed previous findings that approximately 70% of breastfed infants born to mothers living with HIV in low-income settings acquire CMV infection by six months of age. However, the study did not find an association between maternal antiretroviral therapy and the risk of postnatal CMV transmission. It is important to note that in the RCT, antiretroviral therapy was only initiated at the onset of labour.  The effect of maternal antiretroviral therapy taken earlier in pregnancy on the prevention or delay of CMV acquisition remains unknown, although a few observational studies have found that maternal antiretroviral therapy reduces congenital and early postnatal CMV infection. It is biologically plausible that antiretroviral therapy reduces or prevents CMV reactivation in the mother, thus preventing transient episodes of maternal CMV viraemia. This mechanism could explain reduced CMV transmission to the infant (be that before or after birth). HIV-exposed but uninfected infants experience higher morbidity and mortality; any such disease attributable to CMV could therefore potentially be reduced by initiation of antiretroviral therapy earlier in pregnancy.

Africa [9]
Malawi [10]
  • [11]