Repeated polymerase chain reaction complementary to other conventional methods for early detection of HIV infection in infants born to HIV-infected mothers

The efficacy of a polymerase chain reaction (PCR) method for early detection of human immunodeficiency virus (HIV) in infants at risk for HIV infection was assessed. The PCR method was added to the routine laboratory test programme in these patients in 1988. PCR was performed in a total of 26 children at risk (age range 2 days to 58 months), including 17 infants born to HIV-infected mothers, who were followed up clinically from the time of birth for a mean period of 23 months (range 6 to 54) in a prospective study. Twelve children were PCR-positive. Eight had AIDS, ARC or symptoms suggestive of HIV infection. All these patients had at least one culture positive for HIV (6/8) and/or one positive serum p24-antigen test (5/8). One child was repeatedly PCR positive, but asymptomatic as well as virus- and antigennegative. Three asymptomatic children with a single positive PCR result were PCR negative in subsequent tests. Fourteen children with negative PCR did not show clinical or immunological signs suggestive of HIV infection. Their cultures for HIV and antigen-p24 assays were negative. It is concluded that in addition to clinical and immunological parameters PCR is a useful technique for diagnosis of HIV infection in infants born to HIV-infected mothers. However, in case of negative HIV cultures and/or serum p24-antigen tests, single positive PCR results in asymptomatic patients must be interpreted with caution and should be confirmed by repeated tests.     

A prospective study of infants born to women seropositive for human immunodeficiency virus type 1. HIV Infection in Newborns French Collaborative Study Group

Assessment of the risks of transmission of infection with human immunodeficiency virus type 1 (HIV-1) from mother to newborn is difficult, partly because of the persistence for up to a year of maternal antibodies transmitted passively to the infant. To determine the frequency of perinatal transmission of HIV infection, we studied from birth 308 infants born to seropositive women, 62 percent of whom were intravenous drug abusers. Of 117 infants evaluated 18 months after birth, 32 (27 percent) were seropositive for HIV or had died of the acquired immunodeficiency syndrome (AIDS) (n = 6); of the 32, only 2 remained asymptomatic. Another 76 infants (65 percent) were seronegative and free of symptoms, whereas 9 (8 percent) were seronegative but had symptoms suggestive of HIV-1 infection. The infants infected with HIV-1 did not differ from the others at birth with respect to weight, height, head circumference, or rate of malformations, but as compared with newborns who were seronegative at 18 months, their serum IgM levels were higher (78 +/- 81 mg per deciliter vs. 38 +/- 39 mg per deciliter; P less than 0.03) and their CD4 lymphocyte counts were lower (2054 +/- 1221 per cubic millimeter vs. 2901 +/- 1195 per cubic millimeter; P less than 0.006). Neither maternal risk factors nor the route of delivery was a predictor of seropositivity at 18 months; however, 5 of the 6 infants who were breast-fed became seropositive, as compared with 25 of 99 who were not (P less than 0.01). We conclude that approximately one third of the infants born to seropositive mothers will have evidence of HIV-1 infection or of AIDS by the age of 18 months, and that about one fifth of this group will have died.     

The use of viral culture and p24 antigen testing to diagnose human immunodeficiency virus infection in neonates. The HIV Infection in Newborns French Collaborative Study Group.

BACKGROUND. Early diagnosis of human immunodeficiency virus (HIV) infection in infants born to infected mothers is important for the infants' medical care, but the presence of maternal antibodies makes serologic tests uninformative. METHODS. In a cohort study of 181 infants born to HIV-infected mothers, we assessed the diagnostic value of HIV viral culture and testing for the presence of p24 antigen. The infants were tested at birth, again during the first 3 months, then followed and tested at the age of at least 18 months. RESULTS. Of the 181 infants, 3 died of HIV infection and 37 were seropositive after the age of 18 months. Viral cultures at birth were positive in 19 of the 40 infected infants and in none of the uninfected infants, yielding a sensitivity of 48 percent (95 percent confidence interval, 32 to 63 percent) and a specificity of 100 percent (95 percent confidence interval, 97 to 100 percent). By the age of three months, 30 of the 40 infants (75 percent) had positive cultures; again, there were no false positive results among the infants who were tested a second time, of the 141 who remained uninfected. The sensitivity of testing for p24 antigen at birth was only 18 percent, with a specificity of 100 percent. The presence of p24 antigen at birth was associated with the development of early and severe HIV-related disease (P less than 0.04). CONCLUSIONS. Viral culture at birth can correctly identify about half of newborns with HIV infection. The fact that this usually sensitive technique fails to identify about half the ultimately infected neonates suggests that vertical transmission of HIV may occur late in pregnancy or during delivery.     

Direct detection of proviral gag segment of human immunodeficiency virus in peripheral blood lymphocytes by colorimetric PCR assay as a clinical laboratory tool applied to different at-risk populations.

We used a colorimetric polymerase chain reaction (PCR)-based assay in kit form to detect directly human immunodeficiency virus type 1 (HIV-1) proviral gag sequences in peripheral blood cells from 68 healthy blood donors, 51 subjects at risk for HIV infection, 122 patients with HIV-1 infection, 11 patients with indeterminate Western blot (immunoblot) results, 4 blood donors HIV-1 positive by enzyme immunoassay, and 13 children born to HIV-1-seropositive mothers. The results obtained in the blood donors and HIV-1-infected patients demonstrated the high degree of diagnostic specificity and sensitivity of the PCR method. HIV-1 infection was excluded in 10 of the 11 patients with indeterminate Western blot results and in all four enzyme immunoassay-positive blood donors. A diagnosis of HIV infection was ruled out by negative PCR results in 5 of 13 children from seropositive mothers, which excluded vertical transmission of the infection in these cases; these children were younger than 3 months and had positive serological results. Two at-risk patients with negative serological results had positive PCR results. All results were confirmed by conventional PCR. In conclusion, colorimetric PCR, which is commercially available in kit form, is an easy and reliable technique that can be used to detect proviral HIV-1 genomes in blood cells, and despite the limitations owing to HIV genome variability, it is useful in the clinical setting for the diagnosis of HIV infection in selected categories of patients.     

Epidemiologic modeling to evaluate prevention of mother-infant HIV transmission in Ontario

OBJECTIVES: To evaluate the impact of the Ontario HIV screening program to reduce mother-infant HIV transmission, this study estimated the proportion of preventable transmissions that were prevented. METHODS: Using an iterative spreadsheet model, incidences of HIV infection, AIDS, and AIDS mortality in Ontario women were estimated by exposure category. The number of HIV-infected infants born to HIV-infected mothers was then estimated from conception and abortion rates of HIV-infected women of childbearing age and surveillance data. Finally, the proportion of HIV-infected mothers who received antiretroviral prophylaxis (ARP) was assessed. RESULTS: HIV prevalence in 2001 among women of childbearing age was 1.05 per 1000. From 1984-2001, 764 infants were born to HIV-infected mothers and 180 were infected. From mid-1994-2001, 214 (39%) of the estimated 544 HIV-infected mothers were diagnosed; almost all received ARP. Of 118 preventable infections among infants born in this period, 39 (33%) were prevented. In 2001, only 46% of preventable infections were prevented and 11 preventable transmissions occurred. CONCLUSIONS: HIV prevalence among women in Ontario increased >4-fold from 1990 to 2001. Fewer than half of HIV-infected mothers received ARP and preventable HIV infections continue to occur. Measures to further increase uptake of prenatal HIV screening must be instituted.     

Perinatally cotransmitted human herpesvirus 6 is activated in children born with human immunodeficiency virus infection

OBJECTIVE: To evaluate the mother-to-child transmission profile of human immunodeficiency virus (HIV) as well as human herpesvirus 6 (HHV-6) and to examine active replication of HHV-6 in the HIV-infected mothers and their newborns. STUDY DESIGN/METHODS: This polymerase chain reaction (PCR)-based detection was done using DNA from peripheral blood mononuclear cells (PBMCs) and milk cells from the mothers, PBMC from the newborns, and DNA derived from plasma and cell-free milk fluid from mothers and plasma of the newborns. None of the mothers received antiretroviral treatment. RESULTS: HIV was transmitted to 50% newborns and, of 36 total mothers, 8 had actively replicating HHV-6 detectable in their plasma and 2 also had it in the lactosera. Among the neonates. HHV-6 was found in the PBMC DNA of seven and in the plasma fractions of five, the latter five newborns were all HIV-infected at birth. CONCLUSION: Perinatally cotransmitted HHV-6 was always activated in the neonates who were born with HIV infection. Also, HHV-6 can be detected in the milk cells and the activated virus may be present in the lactosera of some of these HlV-infected mothers.     

Broad Spectrum of Time of Detection, Primary Symptoms and Disease Progression in Infants with HIV-1 Infection

 The relationship between time of HIV-1 detection, appearance of symptoms and disease progression was studied in all 24 HIV-1-infected infants from a cohort of 117 children who were born to HIV-1-infected mothers and monitored from birth. HIV isolation from plasma and mononuclear cells, HIV-1 DNA PCR (polymerase chain reaction) and, retrospectively, a quantitative assay for HIV-1 RNA were used for virus detection. Two infants possibly exhibited a symptomatic primary HIV infection. More children with than without symptoms during the first year of life progressed to immunological class 3 (P=0.013) and to AIDS or death (P=0.003) during follow-up. HIV-1 was detected within 4 days of age in 4 of 16 infants: 3 of them became symptomatic within 1 year, as did 6 of the remaining 12 infants (not statistically significant). All four infants in whom virus was detected within 4 days of age progressed to severe immunosuppression, compared to 6 of 14 in whom the virus detection test was initially negative prior to the first positive result (n.s.). Two children with previous repeatedly negative HIV detection tests were diagnosed with HIV-1 infection at 8 and 9 months, respectively. Repeated blood sampling is needed for the diagnosis of HIV-1 infection in perinatally exposed infants, and virus detection tests for exclusion of HIV-1 infection must be used with caution.     

Absence of cardiac toxicity of zidovudine in infants. Pediatric Pulmonary and Cardiac Complications of Vertically Transmitted HIV Infection Study Group

BACKGROUND: Perinatal exposure to zidovudine may cause cardiac abnormalities in infants. We prospectively studied left ventricular structure and function in infants born to mothers infected with the human immunodeficiency virus (HIV) in order to determine whether there was evidence of zidovudine cardiac toxicity after perinatal exposure. METHODS: We followed a group of infants born to HIV-infected women from birth to five years of age with echocardiographic studies every four to six months. Serial echocardiograms were obtained for 382 infants without HIV infection (36 with zidovudine exposure) and HIV-58 infected infants (12 with zidovudine exposure). Repeated-measures analysis was used to examine four measures of left ventricular structure and function during the first 14 months of life in relation to zidovudine exposure. RESULTS: Zidovudine exposure was not associated with significant abnormalities in mean left ventricular fractional shortening, end-diastolic dimension, contractility, or mass in either non-HIV-infected or HIV-infected infants. Among infants without HIV infection, the mean fractional shortening at 10 to 14 months was 38.1 percent for those never exposed to zidovudine and 39.0 percent for those exposed to zidovudine (mean difference, -0.9 percent; 95 percent confidence interval, -3.1 percent to 1.3 percent; P=0.43). Among HIV-infected infants, the mean fractional shortening at 10 to 14 months was similar in those never exposed to zidovudine (35.4 percent) and those exposed to the drug (35.3 percent) (mean difference, 0.1 percent; 95 percent confidence interval, -3.7 percent to 3.9 percent; P=0.95). Zidovudine exposure was not significantly related to depressed fractional shortening (shortening of 25 percent or loss) during the first 14 months of life. No child over the age of 10 months had depressed fractional shortening. CONCLUSIONS: Zidovudine was not associated with acute or chronic abnormalities in left ventricular structure or function in infants exposed to the drug in the perinatal period.     

Postnatal transmission of human immunodeficiency virus type 1 from mother to infant. A prospective cohort study in Kigali, Rwanda.

BACKGROUND. Although transmission of human immunodeficiency virus type 1 (HIV-1) from mother to infant has been well documented during pregnancy and delivery, little is known about the possible transmission of HIV-1 during the postnatal period. METHODS. We conducted a prospective cohort study in Kigali, Rwanda, of 212 mother-infant pairs who were seronegative for HIV-1 at delivery. All the infants were breast-fed. The subjects were followed at three-month intervals, with Western blot assays for antibodies to HIV-1 and testing of mononuclear cells by a double polymerase chain reaction (PCR) using three sets of primers. To evaluate potential risk factors, each mother who seroconverted was matched with three seronegative control women. RESULTS. After a mean follow-up of 16.6 months, 16 of the 212 mothers became seropositive for HIV-1. Of their 16 infants, 9 became seropositive. One infant was excluded from the analysis because of a positive test by PCR on the blood sample obtained at birth. Postnatal seroconversion to HIV-1 occurred in four of the five infants born to the mothers who seroconverted during the first 3 months post partum, and in four infants of the 10 mothers who seroconverted between month 4 and month 21. In all cases, the infant seroconverted during the same three-month period as the mother. The main risk factor for maternal seroconversion was being single. CONCLUSIONS. HIV-1 infection can be transmitted from mothers to infants during the postnatal period. Colostrum and breast milk may be efficient routes for the transmission of HIV-1 from recently infected mothers to their infants.     

Transport of recombinant human CD4-immunoglobulin G across the human placenta: pharmacokinetics and safety in six mother-infant pairs in AIDS clinical trial group protocol 146.

Recombinant CD4-immunoglobulin G (rCD4-IgG) is a 98-kDa human immunoglobulin-like protein that is produced by fusing the gp120 binding domain of CD4 to the Fc portion of the human IgG1 heavy chain. This hybrid molecule was given to human immunodeficiency virus (HIV)-infected pregnant women at the onset of labor by intravenous bolus at 1 mg/kg of body weight (group A; n = 3) and 1 week prior to and at the onset of labor by the same route and at the same dose (group B; n = 3). In addition to pharmacokinetic studies, safety in the mothers and infants was determined through routine chemistries, hematology, and urinalysis; immunologic and HIV infection statuses in the infants were assessed through lymphocyte cultures, p24 antigen level determination, culture of HIV from plasma, PCR, lymphocyte subset enumeration, quantitative immunoglobulin analysis, and lymphocyte proliferation. Thirty minutes after the rCD4-IgG injection, concentrations in maternal serum were 12 to 23 micrograms/ml. These concentrations declined slowly, with initial and terminal half-lives (mean +/- standard deviation) of 9.95 +/- 3.23 and 47.6 +/- 22.3 h, respectively. Infants were born 2.6 to 46.5 h after rCD4-IgG administration; concentrations of rCD4-IgG in cord blood ranged from 28 to 107 ng/ml. The half-life of rCD4-IgG in infants ranged from 5 to 29 h. These data demonstrate that the transfer of rCD4-IgG from the mother to the fetus is rapid and that newborns do not appear to have any difficulty eliminating rCD4-IgG. No safety concerns in mothers or infants were encountered. Although the study did not address the question of efficacy, none of the infants was HIV type 1 infected 36 months later. In summary, these findings document that bifunctional immune molecules can be transported across the placenta, and this general approach may be used in the future to block vertical transmission of HIV type 1.     

Transmission of human immunodeficiency virus (HIV) by blood transfusions screened as negative for HIV antibody

Since early 1985, blood donations in the United States have been screened for antibody to human immunodeficiency virus (HIV). To identify instances of HIV transmission by antibody-negative donations, we investigated 13 persons seropositive for HIV who had received blood from 7 donors who were screened as negative for HIV antibody at the time of donation. Twelve of the 13 recipients had no identifiable risk factors for HIV infection other than the transfusions they had received. On evaluation 8 to 20 months after transfusion, HIV-related illnesses had developed in three recipients, and the acquired immunodeficiency syndrome had developed in one. All seven donors were found to be infected with HIV. On interview, six reported a risk factor for HIV infection, and five had engaged in high-risk activities or had had an illness suggestive of acute retroviral syndrome within the four months preceding their HIV-seronegative donation. Thus, these donors had apparently been infected only recently, and so were negative at the time of blood donation according to available antibody tests. We conclude that there is a small but identifiable risk of HIV infection for recipients of screened blood. To minimize this risk, the reasons for deferral of donation need to be communicated more effectively to blood donors who are at high risk of HIV infection, and new assays that detect HIV infection earlier should be evaluated for their effectiveness in screening donated blood.     

TT virus infection in human immunodeficiency virus type 1 infected mothers and their infants

Serum TT virus (TTV) DNA was determined in 83 human immunodeficiency virus type 1 (HIV 1) infected mothers [46 intravenous drug user and 37 non-intravenous drug user women] and their infants. Twenty-nine (34.9%) mothers were TTV infected. Infection was more frequent among intravenous drug user than non-intravenous drug user mothers [21/46 (45.6%) vs. 8/37 (21.6%); relative risk (RR): 2.1; 95% confidence limits (95% CL): 1.1-4.2; P = 0.023] and among intravenous drug users who carried on injecting than in those who had given it up [10/14 (71.4%) vs. 11/32 (34.3%); RR: 2.1 (95%CL: 1.2-3.7); P = 0. 021]. Infection was not related to age, CD4-positive T-lymphocyte counts, HIV 1 load, hepatitis B (HBV), G/GB-C (GBV-C/HGV), C (HCV) virus exposure. Eight (27.5%) infants born to TTV infected (but none of those born to TTV uninfected) mothers were TTV infected at a median age of 1.5 (range: 0.6-2.8) months. Infants born by vaginal/emergency caesarean delivery were more frequently infected than those born by elective caesarean delivery [7/16 (43.7%) vs. 1/13 (7.6%); RR: 2.1; 95%CL: 1.2-3.5; P = 0.033]. Infection in infants was not related to maternal CD4-positive T-lymphocyte counts, HIV 1 load, and HIV 1, HBV, GBV-C/HGV, or HCV transmission. No infant became TTV infected thereafter. No TTV infected child [follow-up: 31 (median; range: 6-60) months] showed signs of liver disease; five infants cleared TTV DNA after 22 (median; range: 6-60) months. TTV infection in HIV 1 infected women is prevalently related to intravenous drug user. The findings suggest that infants may acquire TTV at birth. Infection may persist without evident liver disease.     

Plasmodium Falciparum malaria and perinatally acquired human immunodeficiency virus type 1 infection in Kinshasa, Zaire. A prospective, longitudinal cohort study of 587 children

BACKGROUND. It is uncertain whether Plasmodium falciparum malaria is more frequent or more severe in children with perinatally acquired human immunodeficiency virus type 1 (HIV-1) infection and whether P. falciparum infection accelerates the progression of HIV-related disease. METHODS. We conducted a prospective, longitudinal cohort study in Kinshasa, Zaire. Two hundred sixty children 5 to 9 months of age who had been born to HIV-1-seropositive mothers and 327 children of the same age who had been born to seronegative mothers were monitored intensively for malaria over a 13-month period. All episodes of fever were evaluated with blood smears for malaria, and children found to be infected with P. falciparum were treated with a standard regimen of oral quinine. RESULTS. A total of 2899 fevers were evaluated, with 271 cases of malaria identified. No statistically significant differences were found in the incidence, severity, or response to therapy of malaria among four well-defined groups of children: those with the acquired immunodeficiency syndrome (AIDS), those who were HIV-1-seropositive throughout the study, those who were born to HIV-1-seropositive mothers but reverted to seronegative, and those who were seronegative throughout the study. During the 13-month period the incidence of malaria in the 36 children with HIV infection in whom AIDS developed was lower, although not significantly so, than in the 37 in whom AIDS did not. CONCLUSIONS. In this study malaria was not more frequent or more severe in children with progressive HIV-1 infection and malaria did not appear to accelerate the rate of progression of HIV-1 disease.     

Is the course of perinatal hepatitis B virus infection influenced by genetic heterogeneity of the virus?

We studied the relations between genetic heterogeneity of pre-C region of hepatitis B virus (HBV) DNA and outcome of HBV infection in 5 infants with perinatal infection, 3 born to antihepatitis B e antigen (HBeAg), and 2 to HBeAg positive mothers. HBV infection developed in the babies at 3–4 months of age, but it resolved with seroconversion to anti-HBs in infants born to anti-HBe positive mothers, while the infection became chronic in the 2 babies born to HBeAg positive mothers. HBV-DNA extracted from the first hepatitis B surface antigen (HBsAg) positive serum sample of each baby was amplified and directly sequenced for the pre-core region. HBV-DNA sequences from 3 babies born to anti-HBe positive mothers showed at position 1896 the contemporary presence of 2 nucleotides (G + A), indicating a mixture of wild-type and "e minus"variant HBV. These findings suggest a possible co-transmission of the 2 viruses from anti-HBe positive mothers to newborns. HBV-DNA from babies born to HBeAg positive mothers showed wild-type sequences only. The results of this study suggest that the outcome of HBV infection in newborns depends not only on the host's immunocompetence and on viremia level in maternal blood, but also on heterogeneity of HBV. Transmission of mixed HBV populations appears associated with an early immunoelimination of the virus, while infection with wild-type HBV alone contributes to induction of chronicity. © 1993 Wiley-Liss, Inc.     

HIV seroconversion during pregnancy and risk for mother-to-infant transmission

Pregnant women infected with HIV-1 were enrolled in a prospective mother-to-infant transmission study from 1992 through 1994 in Bangkok. In participating hospitals, voluntary HIV testing was routinely offered at the beginning of antenatal care and again in the middle of the third trimester of pregnancy. Women who seroconverted to HIV during pregnancy were compared with women who had tested positive on their first antenatal test. Maternal HIV RNA levels were determined during pregnancy, at delivery, and postpartum using RNA polymerase chain reaction (PCR), and infection status in infants was determined by DNA PCR. No infants were breast-fed, but prophylactic antiretroviral therapy was not yet used in Thailand to prevent transmission from mother to infant. Among enrolled women, 16 who seroconverted during pregnancy and 279 who were HIV-1-seropositive at their first antenatal test gave birth. Median plasma RNA levels at delivery were similar for the two groups (17,505 and 20,845 copies/ml, respectively; p =.8). Two (13.3%) of 15 infants born to women who seroconverted and 66 (24.8%) of 266 infants born to previously HIV-seropositive women were infected with HIV (p =.5). There was no increased risk for mother-to-infant HIV transmission and no significant difference in viral load at delivery between HIV-infected women who seroconverted to HIV during pregnancy and those who were HIV-seropositive when first tested.     

The role of interferons in the control of HIV replication in macrophages.

Interferons can suppress the replication of certain retroviruses, including oncogenic murine retroviruses. In recent studies of the Lentivirinae subfamily of Retroviridae, an endogenous, immunologically induced interferon was found to restrict the replication of visna in macrophages. Several studies have shown that the replication of a human lentivirus, the human immunodeficiency virus (HIV), is also susceptible to interferon control. Here we review the evidence that interferons can protect macrophages from HIV in vitro. Macrophages treated with interferons or bacterial lipopolysaccharide (LPS) become essentially nonpermissive for HIV replication. Using the polymerase chain reaction to amplify HIV proviral DNA, we now report that interferon and LPS act to restrict the formation of proviral DNA. Effects on any several steps in the HIV life cycle may explain this data, and single-cycle infection studies are needed to define the precise roles of these agents. Taken together, these findings may explain the restricted replication of HIV in macrophages in vivo and suggest an antiviral role for endogenously produced interferon in the maintenance of the prolonged asymptomatic period which typically follows HIV infection. Interferons are currently undergoing clinical trials to determine if they have antiviral effects in HIV-infected patients.     

Predictors of the acquired immunodeficiency syndrome developing in a cohort of seropositive homosexual men

In a cohort of 1835 homosexual men who were seropositive for human immunodeficiency virus (HIV) on entry into a prospective study, the acquired immunodeficiency syndrome (AIDS) developed in 59 during a median follow-up of 15 months. We matched 5 seropositive controls to each case according to study center and date of enrollment and performed a case-control analysis to determine factors predictive of AIDS. In a multivariate analysis, a decreased number of T helper lymphocytes, an increased number of T suppressor lymphocytes, a low level of antibody to HIV, a high titer of cytomegalovirus antibody, and a history of sex with someone in whom AIDS developed were independently associated with subsequent AIDS. Separate analyses of risk factors for Kaposi's sarcoma and opportunistic infections failed to support previously reported associations between the use of nitrites or an elevated cytomegalovirus-antibody titer and Kaposi's sarcoma. These variables may be markers rather than determinants of disease progression. A vigorous antibody response to HIV infection may confer at least temporary protection against the progression of immunodeficiency to AIDS, or a low level of antibody to HIV may reflect a later stage of infection. The increased risk associated with a history of sex with someone in whom AIDS developed may indicate earlier infection in cases or infection with a more virulent strain of HIV. These results may be useful in counseling HIV-seropositive persons and in designing studies of clinical interventions.     

Prospective study of mother-to-infant transmission of hepatitis C virus (HCV) infection

Seventy-five women with anti-hepatitis C virus (HCV) antibody were enrolled prospectively during pregnancy or at delivery for study of mother-to-child transmission of HCV. Twenty-three women were coinfected with the human immunodeficiency virus (HIV). Seventy babies were monitored for at least 6 months. HCV infection was diagnosed in six infants (8.6%), four of whom were born to anti-HIV–positive mothers. HCV RNA was first detected between 2 and 6 months, and the genotypes of infected babies matched those of their mothers (type 1: n = 4; type 3: n = 2). Identical master sequences of the hypervariable region (HVR1) were detected in a mother–infant pair. In three babies coinfected with HCV and HIV, anti-HCV disappeared between 2 and 7 months, being persistently negative in two cases monitored for 11 and 26 months. Transmitting mothers did not differ significantly from those who did not transmit the infection with anti-HIV, HCV genotypes, and viral load at delivery, but had lower rate of reactivity to C100 by the recombinant immunoblot assay (RIBA) (P < .01). This prospective study confirms transmission of HCV from anti-HIV–negative mothers (4.4% in this series). Absence of anti-C100 antibodies at delivery is apparently related to increased risk of vertical transmission. Seronegative HCV infection can be observed in children coinfected with HIV. J. Med. Virol. 54:12–19, 1998. © 1998 Wiley-Liss, Inc.     

A survey of zidovudine use in pregnant women with human immunodeficiency virus infection.

BACKGROUND AND METHODS. The expanding indications for zidovudine treatment make it important to elucidate the safety and toxicity of this drug for pregnant women and their fetuses. We asked pediatricians and obstetricians at the AIDS (acquired immunodeficiency syndrome) Clinical Trials Units to report information about pregnant women infected with the human immunodeficiency virus (HIV) who were continuing their pregnancies and had received, or were receiving, zidovudine during gestation. RESULTS. Reports of 43 women were received from 17 institutions. Doses of zidovudine ranged from 300 to 1200 mg per day, and 24 women took the drug for at least two trimesters. There were two reported instances of maternal toxicity (one gastrointestinal and one hematologic). No teratogenic abnormalities occurred in the 12 infants with first-trimester exposure to zidovudine. All the infants, including two sets of twins, were born alive. The 38 singleton infants born at term for whom birth weights were reported had a mean birth weight of 3287 +/- 670 g; two cases of intrauterine growth retardation were reported among the infants delivered at term. Hemoglobin values, which were available for 31 newborns, ranged from 7.0 to 12.4 mmol per liter (11.2 to 20 g per deciliter); 3 of the 7 newborns with hemoglobin values of less than 8.4 mmol per liter (13.5 g per deciliter) were born prematurely. CONCLUSIONS. Zidovudine was well tolerated by the pregnant women and was apparently not associated with malformations in the newborns, premature birth, or fetal distress. No pattern of hematologic toxicity was observed in the newborns, but the anemia and growth retardation seen in a minority of the infants could, in part, have resulted from their mothers' treatment with zidovudine.