Editor’s Note
Yüklə 1,08 Mb.
|
- Bu səhifədəki naviqasiya:
- Conclusions
- Table 1 Summary data
- Table 2 Maternal HIV Parameters and CCI
- Table 3 Parameters associated with CCI
- BIRTH PREVALENCE OF CONGENITAL CMV (CCMV) IN HIV EXPOSED INFANTS IN SOUTH AFRICA
- Background
- Study
- Table 2 Logistic regression analysis to determine risk factors for congenital CMV infection in HIV-exposed infants
- Figure 2. Scatterplot summarizing the relationship between maternal CD4 count and infant saliva CMV viral load. There was a negative correlation between the two variables, r = -495, n= 22, p =0.019
Background: Congenital cytomegalovirus (CMV) infection, a leading cause of hearing loss and cognitive impairment, affects 1% of newborns. HIV-exposed children are at higher risk of CMV co-infection (CCI) at birth. NICHD HPTN 040 was a randomized, multi-center clinical trial evaluating the efficacy and safety of additional antiretrovirals (ARV) to standard zidovudine prophylaxis in 1684 HIV-exposed, formula-fed infants born to mothers with no antepartum anti-retrovirals (ARV). Objective: The presence of CCI was evaluated in the NICHD HPTN 040 population of HIV-exposed infants with urine specimens collected at birth. CCI and magnitude of urinary viral load was determined in HIV-uninfected, HIV in utero infected (Positive HIV DNA PCR at birth), and HIV-intrapartum infected infants (Negative HIV DNA PCR at birth with positive PCR later). Methods: The main study was a prospective randomized trial to study the safety and efficacy of adding 1 or 2 antiretroviral (ARV) drugs to standard zidovudine (ZDV) prophylaxis in HIV-exposed, formula-fed infants born to mothers not receiving ARV prior to labour. Infant urines were also tested for CMV DNA by qualitative real time PCR, with quantitation of positive specimens. Chi-square and multivariate logistic regression were used for associations between CCI and HIV infection, demographic / geographic parameters, maternal findings, and infant mortality. Results: A total of 1745 infants were randomized, of which 1734 were enrolled of these 1684 were evaluable. Infants were enrolled in Brazil (n = 1224), South Africa (n = 479), Argentina (n = 28) and the U.S. (n = 13). Urine specimens were available for 879 (52%) of subjects; 53 (6%) were found to be CMV positive (Table 1) with mean virus load of 575,326 copies/ml (range: 200-2,000,000). Among 84 HIV-infected infants, 14 (17%) had CCI as opposed to 39 (5%) of the HIV-exposed, uninfected infants (p< 0.001). CCI was present in 12 (22.6%) of 53 HIV-in utero infections and 2 (6.5%) of 31 HIV-intrapartum infections (p< 0.00001). Median CMV urine virus load for HIV-uninfected, HIV-in utero, and HIV-intrapartum infected infants were 481,454; 761,521; and 1,000,974 copies/ml respectively (Table 2). CCI was not associated with mode of delivery (p=0.74), gestational age (p=0.27), Apgar scores (p=0.46), infant mortality up to age 6 months (p=0.52), maternal HIV virus load (p=0.20) or maternal CD4 count (p=0.91). A multivariate logistic regression analysis revealed older maternal age is a protective risk factors (RF) for CCI (OR: 0.38, 95% CI: 0.16-0.92, p=0.03) and non-white race (OR: 2.96, 95% CI: 1.28-6.83, p=0.01), in utero HIV-infection (OR: 6.42, 95% CI: 3.03-13.6, p< 0.00001), and birth in the Americas versus South Africa (OR: 15.5, 95% CI: 1.10- 217, p=0.0421) were risk factors for CCI (Table 3). Conclusions: CCI in our cohort of HIV-exposed infants born to mothers who received no ART until labour was high (6.5%) as compared to HIV-unexposed populations (1%)
Transplacental HIV acquisition correlates with transplacental CMV acquisition. Increased placental permeability to viruses plays a role in the pathogenesis of congenital CMV acquisition. In utero HIV-infection is strongly associated with CCI and may help explain cognitive deficiencies seen in HIV-infected infants with disease progression. Table 1 Summary data
Maternal age, race, type of delivery, gestational age and Apgar scores were not associated with CCI Table 2 Maternal HIV Parameters and CCI
Maternal virus load at delivery & maternal CD4 cell counts at delivery were NOT associated with CCI Table 3 Parameters associated with CCI
BIRTH PREVALENCE OF CONGENITAL CMV (CCMV) IN HIV EXPOSED INFANTS IN SOUTH AFRICA Dr AM van Niekerk, CYPREHEN study Principal Investigator , Neonatal Service, Mowbray Maternity Hospital, Division of Neonatal Medicine, School of Child and Adolescent Health, University of Cape Town, Cape Town, South Africa Background: CMV is the most prevalent cause of congenital infection worldwide and the leading cause of non-genetic hearing loss in the post-rubella era1. In low seroprevalent areas transmission occurs mostly from primary maternal infection in pregnancy VS via maternal re-activation/ re-infection in seroprevalent areas. The overall incidence is higher in populations with a high seroprevalence where rates of 1-5% is reported.2,3 Despite significant advances in medical diagnostics the vast majority of newborns with congenital CMV(cCMV) are not recognised since cCMV usualy does not cause clinically-apparent disease, 85-90%. Long-term sequele are mainly in the form of SNHL, chorioretinitis and NDDelay. Studies show that symptomatic cCMV disease leads to permanent sequelae in at least 40-58% VS 5-25% , average 13,5% in babies who have no symptoms at all at birth.4,5 Hearing loss: Recent reports show that sub-Saharan Africa accounts for 25% of all congenital and early onset infant permanent bilateral hearing loss in the world, with an estimated prevalence of 6/1000babies affected in the South African public sector.6 In all studies of aetiology of deafness in sub-Saharan Africa- in a1/3 to over ½ of cases- the cause is unknown.7 To summarize, nearly 90% of congenitally CMV infected newborns are asymptomatic at birth2; if symptoms are present they are frequently non-specific.5–7 and when disabilities such as hearing loss become apparent, often months or even years later, it is usually too late to make a retrospective diagnosis that identifies congenital CMV infection as the culprit. A recent systematic review concluded that cCMV was responsible for 15-20% of cases of bilateral moderate to profound SNHL in children.1,8 HIV-infected mothers constitute a special subpopulation, in which an increased frequency of in utero CMV transmission has been consistently documented in Europe and the Americas. The HIV epidemic in sub-Saharan Africa disproportionately affects women of childbearing age. In SA 250 000 HIV positive women give birth every year. With the exception of a single study in Kenya9, conducted on a small sample of infants born to HIV-infected women who used perinatal AZT and a recent study in Zambia10 there are no data on cCMV infection among HIV-exposed infants in Africa.
In our CYPREHEN (CYtomegalovirus PREvalence in HIV-Exposed Newborns) study, we evaluated the prevalence of cCMV in a large sample of HIV-exposed newborns in South Africa: HIV infected mothers were recruited in the immediate postnatal period at Mowbray Maternity Hospital, a secondary level referral hospital in the Western Cape from April to October 2012. Maternal and infant clinical data and newborn saliva swabs were collected. Saliva swabs were assayed by real-time PCR for CMV. A total of 833 HIV-infected mothers delivered 831 live-born infants during the study period and 757 of those mothers were approached for participation during weekdays, of which 737 consented. An additional 11 babies were enrolled during the study training period in March, 2012. Therefore, 90.9% (757/833), of eligible mothers were approached and 97.4 %,( 737/757), agreed to participate. The median (IQR) age at the collection of saliva specimens was 1.0 day.
CMV was detected in 22/748 newborn saliva swabs, giving a prevalence of 2,94%, (95%CI, 1.9- 4.4) in HIV- exposed newborns. Overall, 96% of mothers used prenatal ARV prophylaxis (prenatal AZT 43.9%, HAART 52.1%). Of the 746 mothers for whom prenatal CD4 count information was available, significantly more mothers with CD4 counts < 200 cells/µL had babies with congenital CMV: 6.3% (8/126) compared to 2.3% (14/620) of mothers with CD4 count greater than 200 cells/uL (p = 0.01). Maternal age, type & length of ARV prophylaxis, prematurity, small for gestational age and infant feeding choice were not significantly different between CMV-infected and uninfected infants. Maternal CD4 count less than 200 cells/μL during pregnancy was independently associated with congenital CMV (aOR 2.9; 95% CI, 1.2-7.3) with a p-value of 0.01.(Table 1) Table 1 Comparison of demographic, maternal and newborn characteristics between CMV- infected and uninfected newborns exposed to HIV. Abbreviation: Intrapartum AZT/sdNVP: intrapartum zidovudine with single dose nevirapine
Table 2 Logistic regression analysis to determine risk factors for congenital CMV infection in HIV-exposed infants
As shown in table 2, on logistic regression analysis, maternal CD4 count less than 200 cells/μL was the only factor independently associated with congenital CMV in the overall study population (aOR 2.9; 95% CI, 1.2 – 7.3), p value 0.02. Using the Chi square for trend analysis, a significant association between maternal CD4 counts and intrauterine transmission of CMV was observed, showing an inverse correlation between the two, further supporting the role of maternal immune status and CMV transmission, p value<0.005(Figure 1). Only 2,1% (10/475) of infants born to mothers with CD4 counts >300 cells/μL and 2.8% (4/145) of infants born to mothers with CD4 counts between 200 and 300 VS 6.3%(8/126) of infants with maternal CD4 counts <200 cells/μL had congenital CMV. The proportion of HIV-exposed infants with congenital CMV infection according to maternal CD4 counts was analysed using Chi square for trend analysis (p<0.005). Figure 1: The proportion of HIV-exposed infants with cCMV infection according to maternal CD4 counts was analysed using Chi square for trend analysis (p<0.005).
In addition, a negative correlation between maternal CD4 counts and CMV viral load in saliva of infected infants was noticed in our study suggesting that impaired maternal immunity may have resulted not only in increased CMV transmission but an increased newborn viral load (Figure 2). Figure 2. Scatterplot summarizing the relationship between maternal CD4 count and infant saliva CMV viral load. There was a negative correlation between the two variables, r = -495, n= 22, p =0.019 
Regarding viral load: Many studies where CMV quantitative PCR was used showed that higher viral loads correlated with the likelihood of Hearing loss.11,12. Although a low viral load has been reported to have a very high negative predictive value for subsequent sequelae of CMV, values of viral load measurements between labs can vary widely and thus makes extrapolating results difficult.13,14 There are several limitations to this study: The background prevalence of congenital CMV in the general population and in the pre-ARV era in South Africa is not known. Therefore, it is not possible to determine whether the birth prevalence we observed is higher than expected for the general population, or to delineate the impact of maternal ARV prophylaxis. The anonymous unlinked design of this study precluded ascertainment of infants’ HIV infection status, and clinical follow-up assessments. In addition, maternal viral load data were not routinely available, and thus not collected and maternal prenatal CD4 counts were only obtained at the start of ARV prophylaxis- making it difficult to assess maternal immune status later in pregnancy. Breast milk contamination of samples is unlikely, given that our specimen collection method allowed an interval of at least two hours between infants’ last exposure to breast milk and saliva swab collection. The near identical proportions of breastfed infants between the congenital CMV infants and those without suggest a significant bias is unlikely.
Yüklə 1,08 Mb. Dostları ilə paylaş:
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||