Compartmentalized Cytomegalovirus Replication and Transmission in the Setting of Maternal HIV-1 Infection

Slyker, Jennifer A.; Farquhar, Carey; Atkinson, Claire; Ásbjörnsdóttir, Kristjana; Roxby, Alison C.; Drake, Alison L.; Kiarie, James; Wald, Anna; Boeckh, Michael; Richardson, Barbra A.; Odem‐Davis, Katherine; John‐Stewart, Grace; Emery, Vincent C.

doi:10.1093/cid/cit727

Cited by 43 publications

(51 citation statements)

References 37 publications

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“…In previous studies, infant CMV infection among HIV-uninfected neonates was associated with maternal age, antiretroviral treatment, CD4 + cell count, plasma, and breast milk viral load [15,22]. In the current study, CD4 + cell count and plasma HIV viral load were found to be significantly associated with infant CMV infection, whereas maternal age and antiretroviral status were not.…”

Section: Discussionsupporting

confidence: 53%

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

Chang

Wiener

Dollard

et al. 2015

Aids

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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.

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Section: Discussionsupporting

confidence: 53%

“…The BAN study, however, did not initiate antiretrovirals until the time of labor. High levels of CMV in breast milk of HIV-infected mothers were demonstrated throughout lactation, with highest levels in the first 24 weeks postpartum [22], which correlates with the time of postnatal infant CMV acquisition we observed.…”

Section: Discussionmentioning

confidence: 58%

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

Chang

Wiener

Dollard

et al. 2015

Aids

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“…Breast milk is a main source of MTCTof CMVand is estimated to occur in 40-66% of breast-fed infants in early life [21,22]. In HIV-1-infected mothers, breast milk CMV level and maternal CD4 þ cell count have been shown to be independently associated with early infant CMV acquisition [23]. In a cross-sectional study of HIV-1 -infected breastfeeding women in Zimbabwe, breast milk CMVand EBV levels were independently associated with detection of breast milk HIV-1 RNA after adjustment for indicators of mastitis and plasma HIV-1 RNA concentration [24].…”

Section: Introductionmentioning

confidence: 99%

Cytomegalovirus, and possibly Epstein–Barr virus, shedding in breast milk is associated with HIV-1 transmission by breastfeeding

Viljoen

Tuaillon

Nagot

et al. 2015

Aids

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“…In women who are HIV-positive, a correlation has been made among milk HCMV loads, lower CD4 counts, reduced growth, and infant transmission [18, 27]. However, because comparisons have not been made to mothers who are HIV-negative, it is not known whether maternal HIV causes greater HCMV reactivation, load, or extended secretion in milk.…”

mentioning

confidence: 99%

Increased Cytomegalovirus Secretion and Risks of Infant Infection by Breastfeeding Duration From Maternal Human Immunodeficiency Virus Positive Compared to Negative Mothers in Sub-Saharan Africa

et al. 2016

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BackgroundBreastfeeding imparts beneficial immune protection and nutrition to infants for healthy growth, but it is also a route for human immunodeficiency virus (HIV) and human cytomegalovirus (HCMV) infection. In previous studies, we showed that HCMV adversely affects infant development in Africa, particularly with maternal HIV exposure. In this study, we analyzed infants risks for acquisition of HCMV infection from breastfeeding and compared HIV-positive and HIV-negative mothers.MethodsTwo cohorts were studied in Zambia. (1) Two hundred sixty-one HIV-infected and HIV-uninfected mothers were compared for HCMV deoxyribonucleic acid (DNA) loads and genotypes (glycoprotein gO) in milk from birth to 4 months postpartum. (2) Maternally HIV-exposed and HIV-unexposed infants were compared for HCMV infection risk factors. The second cohort of 460 infants, from a trial of micronutrient-fortified complementary-food to breastfeeding, were studied between 6 and 18 months of age. Human cytomegalovirus seroprevalence was assayed, and logistic regression was used to calculate risk factors for HCMV infection, including maternal HIV exposure and breastfeeding duration.ResultsHuman cytomegalovirus was detected in breast milk from 3 days to 4 months postpartum, with significantly raised levels in HIV-positive women and independent of genotype. In infants, HCMV antibody seroprevalence was 83% by 18 months age. Longer breastfeeding duration increased infection risk in maternally HIV-unexposed (odds ratio [OR] = 2.69 for 18 months vs <12 months; 95% confidence interval [CI], 0.84–8.59; P = .03) and HIV-exposed infants (OR = 20.37 for >6 months vs never; 95% CI, 3.71–111.70; P < .001).ConclusionsProlonged breastfeeding, which is common in Africa, increased risk of HCMV infection in infants. Both HIV-positive and HIV-negative women had extended milk HCMV secretion. Women who were HIV-positive secreted higher HCMV levels, and for longer duration, with their children at increased infection risk. Human cytomegalovirus control is required to maintain health benefits of breastfeeding.

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Compartmentalized Cytomegalovirus Replication and Transmission in the Setting of Maternal HIV-1 Infection

Abstract: Breast milk CMV levels and maternal CD4 count are major determinants of CMV transmission in the setting of maternal HIV-1. Maternal immune reconstitution or lowering breast milk CMV levels may reduce vertical CMV transmission.

Cited by 43 publications

References 37 publications

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

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

Cytomegalovirus, and possibly Epstein–Barr virus, shedding in breast milk is associated with HIV-1 transmission by breastfeeding

Increased Cytomegalovirus Secretion and Risks of Infant Infection by Breastfeeding Duration From Maternal Human Immunodeficiency Virus Positive Compared to Negative Mothers in Sub-Saharan Africa

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