CMV infection may increase risk of mother-to-child HIV transmission

Cytomegalovirus infection during pregnancy or delivery may greatly increase the subsequent risk of foetal or infant HIV infection, Thai researchers report.

Among formula-fed infants of HIV-infected mothers receiving zidovudine prophylaxis, HIV infections were more frequent in infants with congenital or acquired cytomegalovirus (CMV) infection, Woottichai Khamduang and colleagues reported in a retrospective case-control study from a Thai clinical trial cohort published in the advance online edition of the Journal of Acquired Immune Deficiency Syndromes.

Among independent risk factors maternal viral load is acknowledged as being the most important predictor of mother-to-child HIV transmission. While the presence of infant CMV infection has been looked at within the context of HIV infection of mothers and infants, the authors note it has never been subject to multivariate analysis.

In non- HIV-infected populations between 0.1% and 2% of infants become infected with CMV during pregnancy, and 5% - 10% become infected during birth. CMV is a common virus from the family of herpes viruses that may eventually infect the majority of otherwise healthy adults, and in most cases causes no more than a mild viral infection.

However in a minority of infants infected with CMV during pregancy, infection can lead to more serious health problems such as hearing loss and learning difficulties. 

In people with HIV infection who suffer serious immune system damage, including infants, CMV can cause serious AIDS-defining disease in the gastrointestinal tract or in the eye (retinitis).

Among HIV-infected infants rates of infection ranging from 0-26% during pregnancy have been recorded; the two largest studies have shown a 10% transmission rate. Among formula-fed infants a number of studies have shown high overall rates of CMV in HIV-infected infants, the authors of the Thai study note.

In a retrospective case-control study using data and frozen specimens from a non-breastfeeding cohort the authors looked at predictors, including infant CMV infection, of HIV transmission during pregnancy and birth to see whether CMV was independently associated with HIV transmission.

The study population came from a clinical trial that took place in Thailand from 1997 to 2001 to look at the effects of long- and short-term zidovudine monotherapy in the prevention of mother-to-child HIV transmission.

The parent study included 1409 live births of which 97 were HIV-infected.

HIV-infected infants were matched with HIV-uninfected infants according to maternal viral load; so ensuring the elimination of the strongest known risk factor for MTCT. A total of 194 control mothers and 196 control HIV-uninfected infants were included (one HIV uninfected infant had an infected twin and one matched mother had two uninfected infants).

Mothers were not tested for CMV since studies have shown CMV prevalence among pregnant women in Thailand to be close to 100%. Infants were formula-fed from birth. Infant blood samples were tested at birth, six weeks and at four, six, 12 and 18 months of age.

Infants were screened by testing 18-month plasma or serum for CMV antibodies. All earlier samples were tested to time the start of CMV infection.

Maternal baseline CD4 cell counts, length of zidovudine prophylaxis, mode of delivery, sex of infant, prematurity and birth weight were all tested for HIV transmission risk.

Median length of zidovudine prophylaxis was lower among mothers with infant HIV transmission compared to no transmission, 5.4 weeks and 6.8 weeks, (p=0.04) respectively.

Close to 90% (84) of the 97 HIV-infected infants had samples to time the infection. 40% were infected during pregnancy and 58% during delivery.

Neither zidovudine prophylaxis nor CD4 cell count were significantly associated with HIV transmission, whereas prematurity and low birth weight were (p=0.02 and p=0.003, respectively). The authors note this may be explained by the matching of case-controls according to the strongest and most consistent risk factor - maternal viral load.

Other mother/infant characteristics were similar in both sets of mother-infant pairs.

Among HIV-infected infants congenital and overall CMV infections were more common than in HIV-uninfected infants, 14% (as in other studies) compared to 3%; and 84% compared to 63%, respectively. Acquired CMV infection was common to all infants in the study. CMV infection during delivery and the period immediately following birth accounted mostly for the higher percentage found in HIV-infected infants. The authors believe this can be attributed to cervical shedding.

Congenital (OR: 4.9, p=0.009) and overall CMV (OR: 3.0, p<0.001) infection were strongly associated with overall HIV infection

The timing of both HIV and CMV infections are of importance. Congenital CMV was linked to both HIV infection during pregnancy (OR:8.1, p=0.01) and HIV infection acquired during birth (p=0.03). However, CMV infection acquired after birth was not associated with HIV infection during pregnancy (OR: 0.9, p=1.00) but was significantly associated with HIV infection acquired during delivery (OR: 2.5, p=0.04).

The order of the timing and linking of infections, the authors note, suggests that foetal or infant CMV infection predisposes to HIV infection and not the other way around. There is no evidence to support this and it may be because of some unknown confounding factor, they add.

The authors note that it is probable that the two infections are linked in some way, adding it is likely that one viral infection facilitates the other.

The authors note that 85% of HIV-infected infants were co-infected with CMV by 18 months of age and suggest their impaired immune functioning may make them more susceptible to horizontally acquired infections.

The authors conclude that in an analysis of multiple risk factors for mother-to-child transmission in a formula-fed population of HIV-infected mothers “congenital and acquired CMV infections are strong independent predictors of mother-to-child transmission.”

Khamduang W et al. The interrelated transmission of human immunodeficiency virus type 1 and cytomegalovirus during gestation and delivery in the offspring of HIV-infected mothers. Advance online edition JAIDS, doi: 10.1097/QAI.0b013e31822d0433, 2011.