Maternal Viral Load Research Articles

The impact of breastfeeding on the health of HIV-positive mothers and their children in sub-Saharan Africa

We assessed the impact of breastfeeding by women infected with human immunodeficiency virus (HIV)-1 on their morbidity and risk of mortality and on the mortality of their children. We analysed longitudinal data from two previous randomized clinical trials of mother-to-child transmission of HIV conducted between April 2000 and March 2003 in the Republic of Malawi, Africa. Mothers infected with HIV, and their newborns, were enrolled at the time of their child's birth; they then returned for follow-up visits when the child was aged 1 week, 6-8 weeks and then 3, 6, 9, 15, 18, 21 and 24 months. Patterns of breastfeeding (classified as exclusive, mixed or no breastfeeding), maternal morbidity and mortality, and mortality among their children were assessed at each visit. Descriptive and multivariate analyses were performed to determine the association between breastfeeding and maternal and infant outcomes. A total of 2000 women infected with HIV were enrolled in the original studies. During the 2 years after birth, 44 (2.2%) mothers and 310 (15.5%) children died. (Multiple births were excluded.) The median duration of breastfeeding was 18 months (interquartile range (IQR)=9.0-22.5), exclusive breastfeeding 2 months (IQR=2-3) and mixed feeding 12 months (IQR=6-18). Breastfeeding patterns were not significantly associated with maternal mortality or morbidity after adjusting for maternal viral load and other covariates. Breastfeeding was associated with reduced mortality among infants and children: the adjusted hazard ratio for overall breastfeeding was 0.44 (95% confidence interval (CI)=0.28-0.70), for mixed feeding 0.45 (95% CI=0.28-0.71) and for exclusive breastfeeding 0.40 (95% CI=0.22-0.72). These protective effects were seen both in infants who were infected with HIV and those who were not. Breastfeeding by women infected with HIV was not associated with mortality or morbidity; it was associated with highly significant reductions in mortality among their children.

Prevention of mother-to-child transmission of multi-drug resistant HIV-1 using maternal therapy with both enfuvirtide and tipranavir

The management of multi-drug resistant HIV is a complex challenge in daily practice. Of particular concern is the presence of these strains in pregnant females as drug resistance does not only limit therapeutic options for the mother but may also reduce the effectiveness of perinatal prophylaxis. In order to avoid mother-to-child transmission clinicians may feel compelled to prescribe recently approved drugs for which there is none or only limited experience in pregnancy. We present a case of a pregnant female with drug-resistant HIV who received a mega-HAART regimen including the recently approved drugs enfuvirtide and tipranavir. Only limited information is available on perinatal prescription of enfuvirtide and the use of tipranavir in pregnancy has not yet been reported. (excerpt)

Nevirapine Resistance Viral Mutations After Repeat Use of Nevirapine for Prevention of Perinatal HIV Transmission

Nevirapine Resistance Viral Mutations After Repeat Use of Nevirapine for Prevention of Perinatal HIV Transmission

Impact of chloroquine on viral load in breast milk

The anti-malarial agent chloroquine has activity against HIV. We compared the effect of chloroquine (n = 18) to an anti-malarial agent without known anti-HIV-activity, sulfadoxine-pyrimethamine (n = 12), on breast milk HIV RNA levels among HIV-infected breastfeeding women in Zambia. After adjusting for CD4 count and plasma viral load, chloroquine was associated with a trend towards lower levels of HIV RNA in breast milk compared with sulfadoxine-pyrimethamine (P = 0.05). Higher breastmilk viral load was also observed among women receiving presumptive treatment for symptomatic malaria compared with asymptomatic controls and among controls reporting fever in the prior week. Further research is needed to determine the potential role of chloroquine in prevention of HIV transmission through breastfeeding.

Mortality in HIV-Infected and Uninfected Children of HIV-Infected and Uninfected Mothers in Rural Uganda

To estimate 2-year mortality rates in HIV-1-infected and uninfected infants born to HIV and HIV mothers. Data are from a prospective study in rural Rakai District, Uganda. Infant HIV status (determined by polymerase chain reaction) was evaluated at 1 to 6 weeks postpartum and during breast-feeding, and maternal HIV viral load and CD4 levels were measured at the postpartum visit. Multivariate Cox proportional hazards models and Kaplan-Meier survival analysis were used to assess survival of infants by maternal and infant HIV status and by quartiles of viral load. Log-rank tests were used to test the equality of survival functions. Of the 4604 pregnant women, 16.9% were HIV, and the proportion of children infected was 20.9%. Median survival of HIV-infected infants was 23 months. Two-year child mortality rates were 128 of 1000 children born to HIV mothers, 165.5 of 1000 uninfected children born to HIV mothers, and 540.1 of 1000 HIV-infected children (P < 0.0001). Compared with children of HIV mothers, the hazard of child mortality was 2.04 (P < 0.001) if the mother was HIV and 3.78 (P < 0.001) if the infant was also infected. In the adjusted model, the highest quartiles of log10 HIV viral load in infants and mothers were associated with significantly increased hazard of child mortality (hazard ratio [HR] = 8.54 and HR = 2.50, respectively). Maternal CD4 counts <200 cells/mL were also significant predictors of child mortality (HR = 2.61). A total of 67.6% of HIV-infected children with viral loads above the median died by the age of 2 years and are in need of early antiretroviral therapy (ART). More than half of HIV-infected infants died at less than 2 years of age. Therefore, ART may need to be initiated earlier in HIV-infected African children.

Zinc supplementation to HIV-1-infected pregnant women: Effects on maternal anthropometry, viral load, and early mother-to-child transmission

To examine the effect of zinc supplementation to HIV-1-infected pregnant women on viral load, early mother-to-child transmission of HIV (MTCT), and wasting. Double-blind placebo-controlled randomized clinical trial. Antenatal clinic in Dar es Salaam, Tanzania. Four hundred HIV-1-infected pregnant women. Women 12-27 weeks of gestation were randomly assigned to receive a daily oral dose of 25 mg zinc or placebo from the day of the first prenatal visit until 6 weeks postdelivery. Weight and mid-upper arm circumference (MUAC) were measured monthly. HIV status of the babies was assessed at birth and at 6 weeks postpartum. Viral load was assessed in a random sample of 100 women at baseline and at the end of the study. Zinc had no effects on maternal viral load or early MTCT. Supplementation was related to a significant threefold increase in the risk of wasting (reaching a MUAC value <22 cm) during an average 22 weeks of observation (RR=2.7, 95%CI=1.1, 6.4, P=0.03), and to a 4 mm decline in MUAC during the second trimester (P=0.02). Zinc supplementation to HIV-infected pregnant women offers no benefits on viral load or MTCT. The clinical relevance of an apparent decrease in MUAC associated with zinc supplementation is yet to be ascertained. These findings together with the lack of effect on fetal outcomes (reported previously) do not provide support for the addition of zinc supplements to the standard of prenatal care among HIV-infected women.

High Maternal HIV-1 Viral Load During Pregnancy Is Associated With Reduced Placental Transfer of Measles IgG Antibody

Studies among HIV-1-infected women have demonstrated reduced placental transfer of IgG antibodies against measles and other pathogens. As a result, infants born to women with HIV-1 infection may not acquire adequate passive immunity in utero and this could contribute to high infant morbidity and mortality in this vulnerable population. To determine factors associated with decreased placental transfer of measles IgG, 55 HIV-1-infected pregnant women who were enrolled in a Nairobi perinatal HIV-1 transmission study were followed. Maternal CD4 count, HIV-1 viral load, and HIV-1-specific gp41 antibody concentrations were measured antenatally and at delivery. Measles IgG concentrations were assayed in maternal blood and infant cord blood obtained during delivery to calculate placental antibody transfer. Among 40 women (73%) with positive measles titers, 30 (75%) were found to have abnormally low levels of maternofetal IgG transfer (<95%). High maternal HIV-1 viral load at 32 weeks' gestation and at delivery was associated with reductions in placental transfer (P < 0.0001 and P = 0.0056, respectively) and infant measles IgG concentrations in cord blood (P < 0.0001 and P = 0.0073, respectively). High maternal HIV-1-specific gp41 antibody titer was also highly correlated with both decreased placental transfer (P = 0.0080) and decreased infant IgG (P < 0.0001). This is the first study to evaluate the relationship between maternal HIV-1 viremia, maternal HIV-1 antibody concentrations, and passive immunity among HIV-1-exposed infants. These data support the hypothesis that high HIV-1 viral load during the last trimester may impair maternofetal transfer of IgG and increases risk of measles and other serious infections among HIV-1-exposed infants.

Does Severity of HIV Disease in HIV-Infected Mothers Affect Mortality and Morbidity among Their Uninfected Infants?

Rates of perinatal human immunodeficiency virus (HIV) transmission are higher among HIV-infected mothers with more advanced disease, but effects of maternal disease on HIV-uninfected offspring are unclear. We investigated the hypothesis that the severity of HIV disease and immune dysfunction among mothers is associated with increased morbidity and mortality among their uninfected infants. In a birth cohort of 620 HIV-uninfected infants born to HIV-infected mothers in Lusaka, Zambia, we investigated associations between markers of more advanced maternal HIV disease and child mortality, hospital admissions, and infant weight through 4 months of age. Mortality in the cohort of uninfected infants was 4.6% (95% confidence interval [CI], 2.8-6.3) through 4 months of age. Infants of mothers with CD4+ T cell counts of <350 cells/microL were more likely to die (hazard ratio [HR], 2.87; 95% CI, 1.03-8.03) and were more likely to be hospitalized (HR, 2.28; 95% CI, 1.17-4.45), after adjusting for other factors, including maternal death and low birth weight. The most common cause of infant death and hospitalization was pneumonia and/or sepsis. A maternal viral load of >100,000 copies/mL was associated with significantly lower child weight through 4 months of age. Children born to HIV-infected mothers with advanced disease who escaped perinatal or early breastfeeding-related HIV infection are nonetheless at high risk of mortality and morbidity during the first few months of life. HIV-related immunosuppression appears to have adverse consequences for the health of infants, in addition to risks of vertical transmission.

Vertical transmission of HIV in Ghanaian women diagnosed in cord blood and post‐natal samples

HIV RNA detection in the newborn is the main diagnostic tool for vertical transmission. Most infections are thought to occur peri- or post-natally, hence preventive antiviral therapy administered days before and during delivery. This study used cord blood for molecular diagnosis, examined viral load and HIV-1 subtypes as determinants of transmission, and compared molecular variability of maternal, cord blood, and post-natal quasispecies. Ninety-seven seropositive mother-cord blood paired plasmas from Ghana were tested for HIV RNA. Viral load was quantified and a subgroup of 45 random women samples was typed and subtyped. HIV-1 from infected pairs was cloned, sequenced, and analyzed phylogenetically. The prevalence of HIV infection in pregnant women was 3.3%. 13/97 cord blood samples (13.5%) contained HIV RNA. No correlation between either viral load at labor (range 10(3)-10(7)) or HIV-1 subtype and in utero transmission was found. In both transmitting and non-transmitting mothers, 56% of HIV-1 strains were CRF02_AG. In three pairs, maternal and cord blood quasispecies were closely related, suggesting late pregnancy or perinatal transmission, while in four pairs, genetic distances suggested transmission earlier during gestation. Maternal viral load and genotype did not correlate with HIV-1 pre-natal transmission. HIV infection during gestation appears relatively frequent.

A randomized trial of two postexposure prophylaxis regimens to reduce mother-to-child HIV-1 transmission in infants of untreated mothers

Single-dose nevirapine (NVP) prophylaxis to mother and infant is widely used in resource-constrained settings for preventing mother-to-child transmission (MTCT) of HIV-1. Where women do not access antenatal care or HIV testing, postexposure prophylaxis to the infant may be an important preventative strategy. This multicentre, randomized, open-label clinical trial (October 2000 to September 2002) in South Africa compared single-dose NVP with 6 weeks of zidovudine (ZDV), commenced within 24 h of delivery among 1051 infants whose mothers had no prior antiretroviral therapy. HIV-1 infection rates were ascertained at birth, and at 6 and 12 weeks of age. Kaplan-Meier survival methods were used to estimate HIV-1 infection rates in an intention-to-treat analysis. Overall, 6 week and 12 week MTCT probability was 12.8% [95% confidence interval (CI),10.5-15.0] and 16.3% (95% CI,13.4-19.2), respectively. At 12 weeks, among infants who were not infected at birth, 24 (7.9%) infections occurred in the NVP arm and 41 (13.1%) in the ZDV arm (log rank P = 0.06). Using multivariate analysis, factors associated with infection following birth were ZDV use [odds ratio (OR), 1.8; 95% CI,1.1-3.2; P = 0.032), maternal CD4 cell count < 500 x 10(6) cells/l (OR, 2.5; 95% CI,1.3-5.0; P = 0.007), maternal viral load > 50 000 copies/ml (OR, 3.6; 95% CI,2.0-6.2; P < 0.0001) and breastfeeding (OR, 2.2; 95% CI,1.3-3.8; P = 0.006). A single-dose of NVP given to infants offers protection against HIV-1 infection and should be a strategy used in infants of mothers with untreated HIV infection.

50 Vertical HCV Transmission in HIV-HCV Coinfected Mothers is Influenced by Nevirapine.

INTRODUCTION Vertical transmission of hepatitis C virus (HCV) is greater in infants from pregnant women HCV-HIV (human immunodeficiency virus) coinfected when compared with infants from HCV infected HIV negative mothers. The mechanism of this greater rate of transmission remains unclear. Highly active antiretroviral therapy immune restoration has been implicated in potential adverse effects such as severe presentation of HCV disease. OBJECTIVE to determine the HCV vertical transmission rate from HCV-HIV coinfected mothers, in correlation with antiretroviral treatment. METHODS 18 coinfected pregnant women and their infants were studied. HIV status (viral load, CD4, CD8), antiretroviral treatment, HCV-RNA viral load were analysed in the mothers early in pregnancy and closest to delivery. HCV-RNA viral load was determined in the newborns at birth, 15 days, 1, 2, 5 and 8 months. Vertical transmission was defined as two positive determinations in the newborn. RESULTS During the pregnancy we found a significant decrease of HIV viral load (p<0.01) and increase of CD4 (p<0.05) and HCV viral load (p<0.05). HCV vertical transmission rate was 22%. It was not related to mother's age, coinfection duration, gestational age and birth weight neither to CD4, CD8, HIV and HCV viral load during the pregnancy. Different treatment protocols were used: NRTI (AZT, 3TC, D4T, DDC, DDI), NRTI + IP (RTV), NRTI + NNRTI (NVP). Vertical transmission was not influenced by the number of drugs, neither by NRTI or IP treatment. Only mothers treated with NVP transmitted HCV (transmission rate 50 % (p< 0.05). All the infants HCV infected had HCV viral load negative at birth and at 15 days of life. CONCLUSION Nevirapine strongly influenced the vertical transmission of HCV from coinfected mothers. Vertical transmission was not related to maternal HCV viral load. All infected infants were negative at birth, suggesting the presence of a virus reservoir.

Effect ofCCR2Chemokine Receptor Polymorphism on HIV Type 1 Mother-to-Child Transmission and Child Survival in Western Kenya

The effect of CCR2 polymorphism on HIV-1 mother-to-child transmission and disease progression has not been explored in depth within Africa. As the CCR2-64I variant of this putative HIV coreceptor has been associated with slower progression to AIDS in adults, the current study was undertaken to examine the relationship between CCR2 polymorphism and HIV-1 perinatal transmission and child survival in western Kenya. CCR2 genotype was determined for 445 HIV-seropositive mothers and their infants. The CCR2-64I allele frequency of both mothers and children did not differ by HIV-1 transmission status, regardless of maternal viral load, viral subtype, immune status, or placental malaria status. For infants who acquired HIV perinatally (n = 78), there was no association between CCR2 genotype and viral load upon infection or survival rate over the 2-year follow-up. Our results do not indicate an effect of CCR2-64I on perinatal HIV transmission and survival in Kenyan children.

Fatores protetores e de risco envolvidos na transmissão vertical do HIV-1

This study aimed to evaluate maternal and fetal factors related to vertical transmission of HIV-1. Participants included 47 mother-child pairs. Behavioral, demographic, and obstetric data were obtained through interviews. Data related to delivery and newborns were collected from registries in the maternity hospitals. During the third trimester of pregnancy, CD4+ T lymphocytes and maternal viral load were measured. Mean age of the mothers was 25 years and 23.4% of the pregnant women were primigravidae. The most prevalent behavioral factor was lack of condom use. 48.9% of the women presented a CD4+ count greater than 500 cells/mm3, and 93.6% belonged to clinical category A. 95.7% of the women received zidovudine prophylaxis during pregnancy or childbirth, and the medication was also administered to all the neonates. 50.0% of patients were submitted to elective cesareans. Despite several risk and protective factors, none of the children was infected. Vertical transmission is an outcome of an imbalance among factors, with a predominance of risk over protective factors.

Gender Differences in Perinatal HIV Acquisition Among African Infants

We investigated gender-specific risks of mother-to-child transmission (MTCT) at birth and at 6 to 8 weeks among infants born to HIV-infected African women. Follow-up study of infants enrolled in 2 randomized, phase III, clinical trials to prevent MTCT, conducted in Blantyre, Malawi, in southeast Africa. Infants were enrolled at birth and monitored postnatally, and their HIV status was assessed at birth and at 6 to 8 weeks (assessment beyond 6-8 weeks is ongoing). Statistical analyses were stratified according to gender, and comparisons were made with descriptive, univariate, and multivariate statistical tests. MTCT was estimated at birth and at 6 to 8 weeks among infants who were not infected at birth. Overall, 966 boys and 998 girls were enrolled. The rate of HIV transmission at birth was 9.5% (187 of 1964 infants). However, at birth significantly more girls (12.6%) than boys (6.3%) were infected with HIV. This association remained significant after controlling for maternal viral load and other factors. Among infants who were uninfected at birth, 8.7% (135 of 1554 infants) acquired HIV by 6 to 8 weeks; of these infants, more girls acquired HIV (10.0%), compared with boys (7.4%). Female infants may be more susceptible to HIV infection before birth and continuing after birth. Alternatively, in utero mortality rates of HIV-infected male infants may be disproportionately higher and thus more HIV-infected female infants are born. In areas of sub-Saharan Africa, where HIV infection rates are high among women of reproductive age, the magnitude of the gender transmission differences observed in this study could have clinical, preventive, and demographic implications.

Mother-to-Child Transmission of HIV Infection in the Era of Highly Active Antiretroviral Therapy

Very low rates of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) are achievable with use of highly active antiretroviral therapy (HAART). We examine risk factors for MTCT in the HAART era and describe infants who were vertically infected, despite exposure to prophylactic MTCT interventions. Of the 4525 mother-child pairs in this prospective cohort study, 1983 were enrolled during the period of January 1997 through May 2004. Factors examined included use of antiretroviral therapy during pregnancy, maternal CD4 cell count and HIV RNA level, mode of delivery, and gestational age in logistic regression analysis. Receipt of antenatal antiretroviral therapy increased from 5% at the start of the HAART era to 92% in 2001-2003. The overall MTCT rate in this period was 2.87% (95% confidence interval [CI], 2.11%-3.81%), but it was 0.99% (95% CI, 0.32%-2.30%) during 2001-2003. In logistic regression analysis that included 885 mother-child pairs, MTCT risk was associated with high maternal viral load (adjusted odds ratio [AOR], 12.1; P=.003) and elective Caesarean section (AOR, 0.33; P=.04). Detection of maternal HIV RNA was significantly associated with antenatal use of antiretroviral therapy, CD4 cell count, and mode of delivery. Among 560 women with undetectable HIV RNA levels, elective Caesarean section was associated with a 90% reduction in MTCT risk (odds ratio, 0.10; 95% CI, 0.03-0.33), compared with vaginal delivery or emergency Caesarean section. Our results suggest that offering an elective Caesarean section delivery to all HIV-infected women, even in areas where HAART is available, is appropriate clinical management, especially for persons with detectable viral loads. Our results also suggest that previously identified risk factors remain important.

Prevention of Mother-to-Child Transmission of HIV Infection

It has been 10 years since a study of perinatal zidovudine regimen showed that it prevented mother-to-child transmission of HIV in 67% of cases [1]. The article from the European Collaborative Study in this issue of Clinical Infectious Diseases [2] summarizes how far we have come over the past 10 years in the developed world. Treatment of HIV-infected pregnant women has increased such that >90% of HIV-infected women receive HAART. The overall rate of mother-to-child transmission of HIV has been dramatically reduced to 1%. The European Collaborative Study [2] confirm that maternal viral load is the key risk factor for mother-to-child transmission of HIV and that the suppression of viral replication through administration of potent combinations of antiretroviral drugs markedly reduces the risk of mother-to-child transmission. In HAART recipients, the only other intervention that significantly reduced motherto-child transmission of HIV was elective Caesarean section delivery. Although the European Collaborative Study article [2]

Maternal plasma viral load and neutralizing/enhancing antibodies in vertical transmission of HIV: A non-randomized prospective study

BackgroundWe examined the association and interaction between maternal viral load and antibodies in vertical transmission of HIV in a non-randomized prospective study of 43 HIV-1 infected pregnant women who attended the San Juan City Hospital, Puerto Rico, and their 45 newborn infants. The women and infants received antiretroviral therapy.MethodsA nested PCR assay of the HIV-1 envelope V3 region and infant PBMC culture were performed to determine HIV status of the infants. Maternal and infant plasma were tested for HIV neutralization or enhancement in monocyte-derived macrophages.ResultsTwelve (26.7%) infants were positive by the HIV V3 PCR assay and 3 of the 12 were also positive by culture. There was a trend of agreement between high maternal viral load and HIV transmission by multivariate analysis (OR = 2.5, CI = 0.92, p = 0.0681). Both maternal and infant plasma significantly (p = 0.001 for both) reduced HIV replication at 10-1 dilution compared with HIV negative plasma. Infant plasma neutralized HIV (p = 0.001) at 10-2 dilution but maternal plasma lost neutralizing effect at this dilution. At 10-3 dilution both maternal and infant plasma increased virus replication above that obtained with HIV negative plasma but only the increase by maternal plasma was statistically significant (p = 0.005). There were good agreements in enhancing activity in plasma between mother-infant pairs, but there was no significant association between HIV enhancement by maternal plasma and vertical transmission.ConclusionAlthough not statistically significant, the trend of association between maternal viral load and maternal-infant transmission of HIV supports the finding that viral load is a predictor of maternal-infant transmission. Both maternal and infant plasma neutralized HIV at low dilution and enhanced virus replication at high dilution. The antiretroviral treatments that the women received and the small sample size may have contributed to the lack of association between HIV enhancement by maternal plasma and vertical transmission.

Risk Factors for In Utero and Intrapartum Transmission of HIV

To identify predictors of in utero and intrapartum HIV-1 transmission in infants born in the Women and Infants Transmission Study between 1990 and 2000. In utero HIV-1 infection was defined as an infant with the first positive HIV-1 peripheral blood mononuclear cell culture and/or DNA polymerase chain reaction assay at 7 days of age or younger; intrapartum infection was defined as having a negative HIV-1 culture and/or DNA polymerase chain reaction assay at 7 days of age or younger and the first positive assay after 7 days of age. Of 1709 first-born singleton children with defined HIV-1 infection status, 166 (9.7%) were found to be HIV-1 infected; transmission decreased from 18.1% in 1990-1992 to 1.6% in 1999-2000. Presumed in utero infection was observed in 34% of infected children, and presumed intrapartum infection, in 66%. Among infected children, the proportion with in utero infection increased over time from 27% in 1990-1992 to 80% (4 of 5) in 1999-2000 (P = 0.072). Maternal antenatal viral load and antiretroviral therapy were associated with risk of both in utero and intrapartum transmission. Controlling for maternal antenatal viral load and antiretroviral therapy, low birth weight was significantly associated with in utero transmission, while age, antenatal CD4 cell percentage, year, birth weight, and duration of membrane rupture were associated with intrapartum transmission. Although there have been significant declines in perinatal HIV-1 infection over time, there has been an increase in the proportion of infections transmitted in utero.

Prenatal ultrasound findings in 93 cases of fetal infection with cytomegalovirus. Correlation with amniotic fluid viral load and outcome

CYTOMEGALOVIRUS. CORRELATION WITH AMNIOTIC FLUID VIRAL LOAD AND OUTCOME MASAMI YAMAMOTO, FRANCOIS JACQUEMARD, OLIVIER PICONE, JEANMARC COSTA, YVES VILLE, CHI Poissy-St Germain, Poissy, France, Institute de Puericulture de Paris, Service de Medicine Foetale, Paris, France, Universite Paris Ouest SQY-V CHI Poissy St Germain en Laye, Obstetrics and Gynecology Service, Poissy, France, American Hospital of Paris, Service de Biologie Moleculaire Marcel Dassault, Neuilly sur Seine, France OBJECTIVE: To identify all ultrasound findings in fetuses infected with CMV and its relation with amniotic fluid viral load and outcome. STUDY DESIGN: All cases of fetal cytomegalovirus infection from maternal primary infection and diagnosed by viral genome amplification by PCR in amniotic fluid, between 1997-2004 were reviewed for ultrasound features, time of maternal seroconversion and amniotic fluid viral load. RESULTS: 70 of 93 infected fetuses at 25 [17-36] weeks had ultrasound features of infection and 46% of them showed more than one abnormality. The most frequent findings were ventriculomegaly (27%), hyperechogenic bowel (24%), growth restriction (19%), intracerebral hyperechogenicity (19%), microcephaly (17%), oligohydramnios (11%), hepatosplenomegaly (9%) and isolated ascitis (7%). Amniotic fluid viral load (AFVL) was 2.4 ! 107 [102-4 ! 107] cp/mL increased with gestational age (R = 0.4, P = 7 ! 10-4). Termination of pregnancy was performed for infection in 63 (67%) of the cases as confirmed by postmortem examination. There was 1 neonatal death in a severe congenital infection with preterm delivery at 32 weeks and 1 case of severe neurological impairment. Fetuses without US features presented a normal follow-up. There was no correlation between amniotic fluid viral load and the presence or severity of ultrasound abnormalities nor with outcome. Maternal seroconversion in the first, second and third trimester presented US abnormalities in 56%, 44% and 25% of cases respectively. Ultrasound features were progressive with gestation in at least 46% of cases. The virus is excreted by fetal urine and accumulates in the amniotic fluid irrespective of the severity of the fetal infection. CONCLUSION: The earlier the seroconversion, the higher the incidence of US findings. AFVL does not contribute valuably to establish the prognosis of the disease. The absence of ultrasound findings on targeted serial ultrasound examination is reassuring.

Sperm washing, use of HAART and role of elective Caesarean section

Today, 50% of people living with HIV are women and most have been sexually infected. Highly active antiretroviral therapy (HAART) reduces the rates of both sexual and vertical infection, but maximum protection is achieved with sperm washing and elective Caesarean section. Men taking HAART have lower seminal concentration of HIV, and sexual transmission may be reduced. However, a certain percentage of aviraemic men retain viral presence in semen, and unprotected intercourse to achieve fertilization must be discouraged as it carries the risk of sexual transmission of the virus. HIV-discordant couples should be informed that sperm washing can remove HIV from semen, allowing conception without the risk of infection for the seronegative female and eventually the child. In HIV-positive women, perinatal transmission of HIV can be curtailed to less than 2% by using HAART to decrease maternal viral load and offering prenatal preexposure prophylaxis of the fetus, and elective Caesarean section. Each intervention carries specific risks and benefits. The contribution of each preventive arm in achieving fetal protection can only be crudely measured and optimal obstetric management must involve discussion with the pregnant woman of the pros and cons of each strategy. In HIV-positive men taking HAART, seminal viral load is decreased but not eliminated and fertilization should be achieved through sperm washing to offer maximum protection for the uninfected female. Pregnant HIV-positive women on antiretroviral medication have a reduced risk of transmitting the virus, but should still be counselled about the possibility to further limit the chances of infecting their infant through elective Caesarean section.