Addition of single-dose tenofovir and emtricitabine to intrapartum nevirapine to reduce perinatal HIV transmission

OBJECTIVE: To determine the impact of adjuvant single-dose peripartum tenofovir/emtricitabine (TDF/FTC) on intrapartum/early postpartum HIV transmission. METHODS: In the setting of routine short-course zidovudine (ZDV) and peripartum nevirapine (NVP) for perinatal HIV prevention, participants were randomized to single-dose TDF (300 mg)/FTC (200 mg) or to no intervention in labor. Six-week infant HIV infection was compared according to actual-use drug regimens. RESULTS: Of 397 women randomized, 355 (89%) had infants who were alive and active at 6 weeks postpartum. Of these, 18 (5.1%) were infected in utero and 6 (1.8%) were infected intrapartum/early postpartum. Among the 243 who used ZDV and NVP, intrapartum/early postpartum transmission was not reduced among infants whose mothers received TDF/FTC compared with those who did not (2 of 123 [1.6%] vs. 3 of 109 [2.8%]; P = 0.67). Among the 49 infants whose mothers did not receive antenatal ZDV but who had confirmed NVP ingestion, transmission similarly did not differ (0 of 19 [0%] vs. 1 of 26 [3.4%]). TDF/FTC was not significantly associated with reduced overall transmission (odds ratio [OR] = 0.7, 95% confidence interval [CI]: 0.3 to 1.6), even when other antiretroviral drugs were considered (adjusted OR = 0.8, 95% CI: 0.3 to 1.8). CONCLUSIONS: Adjuvant peripartum single-dose TDF/FTC did not reduce perinatal transmission. Whether a higher dose might be effective remains unknown but should be studied in settings in which NVP is used without antenatal ZDV.     

Maternal characteristics associated with antenatal, intrapartum, and neonatal zidovudine use in four US cities, 1994-1998

OBJECTIVES: To evaluate implementation of 1994 United States Public Health Service guidelines for zidovudine (ZDV) use in HIV-infected women and their newborns by describing the prevalence of use of perinatal ZDV and other antiretrovirals and by investigating determinants of not receiving perinatal ZDV. DESIGN/METHODS: The Perinatal AIDS Collaborative Transmission Study is a prospective cohort study designed to collect information related to mother-to-child HIV transmission that was conducted in New York City (NY), Newark (NJ), Baltimore (MD), and Atlanta (GA), U.S.A. The current analysis was restricted to infants born between July 1994 and June 1998. RESULTS: Utilization rates for antenatal, intrapartum, and neonatal ZDV increased from 41% to 70% during the 4-year period. Use of combination antiretrovirals increased from fewer than 2% of women in 1994 to 1995 to 35% in 1997 to 1998. Antenatal and neonatal ZDV use increased each year, but intrapartum ZDV use reached a plateau after 1996. Mother-infant pairs with the following characteristics were less likely to have received a complete 3-part ZDV regimen: older maternal age, CD4 count >500 cells/microl, preterm birth, cocaine or heroin use during pregnancy, positive newborn drug screen test result, and smoking or alcohol use during pregnancy. By multivariate logistic regression adjusted for hospital and year of birth, cocaine or heroin use during pregnancy (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.6-3.3), maternal CD4 count (OR, 0.4; 95% CI, 0.2-0.8; comparing <200 with >500 cells/microl), and preterm birth (OR, 1.6; 95% CI, 1.1-2.5) remained independently associated with not receiving the complete ZDV regimen. CONCLUSIONS: ZDV use by pregnant HIV-infected women and their infants has increased dramatically since publication of the 1994 guidelines. Nevertheless, women who abuse substances, give birth preterm, or have less advanced immunosuppression, were at substantial risk of not receiving the complete ZDV regimen.     

HIV-1 viral load and other risk factors for mother-to-child transmission of HIV-1 in a breast-feeding population in Cote d'Ivoire

Short-course antiretroviral regimens have been evaluated to reduce mother-to-child transmission of HIV in resource-limited settings. This report from Abidjan, Cote d'Ivoire, examines the risk factors for HIV transmission by 1 and 24 months among breast-feeding women. Eligible HIV-1-seropositive pregnant women enrolled in this randomized double-blind clinical trial were randomly assigned to receive either oral zidovudine (ZDV) (n = 126) prophylaxis or placebo (n = 124). Maternal prophylaxis began at 36 weeks of gestation (300 mg ZDV twice daily antepartum and 300 mg every 3 hours intrapartum); there was no neonatal prophylaxis component. The cumulative risk of transmission in the treatment group was 11.9% and 22.1% by 1 and 24 months, respectively. In adjusted analyses, viral load at enrollment was the strongest predictor of transmission (per log increment: odds ratio [OR] = 4.8, 95% confidence interval [CI]: 2.5-9.5 at 1 month; OR = 5.7; 95% CI: 3.1-10.8 at 24 months). Overall, ZDV prophylaxis was not significantly protective for infection at 1 or 24 months. Comparing ZDV with placebo following dichotomization of viral load (<50,000 vs. > or =50,000 copies/mL) at enrollment, however, there was a significant effect of ZDV seen only among those women with a low viral load at enrollment. The substantial risk of transmission despite ZDV prophylaxis, particularly among those with higher viral loads, underscores the need to find more effective regimens appropriate for use in resource-limited settings.     

Evaluation of a systematic substitution of zidovudine for stavudine-based HAART in a program setting in rural Cambodia

OBJECTIVE: To evaluate a treatment strategy of substituting zidovudine (ZDV) for stavudine (d4T)-based highly active antiretroviral therapy (HAART), aimed at preventing d4T-associated toxicity, in a programmatic setting in rural Cambodia. METHODS: Survival probability, CD4 gain, anemia incidence, and factors associated with severe anemia were analyzed in a cohort of adult patients switched from d4T- to ZDV-containing regimens from March 2006 to March 2007. RESULTS: Among 527 patients systematically switched to ZDV after d4T-based HAART for a median of 18 months, 4 (0.8%) patients died, 2 (0.4%) were lost to follow-up, 18 (3.4%) were transferred out, and 503 (95.4%) remained on HAART. Median CD4 gain was +263.5 cells/microL (interquartile range: 89.25-369.5) at 24 months. Within 1 year after the switch, 21.9% and 7.1% of patients developed anemia (grades 1-4) and severe anemia (grades 3-4), respectively. Low body mass index (< or =18) and low CD4 count (<200 cells/microL) at the time of switch were factors associated with severe anemia. Additional follow-up visits for laboratory monitoring and adherence counseling, increased absenteeism from work, and transportation costs for the patients were noted. CONCLUSIONS: The switch strategy of substituting ZDV for d4T-based HAART led to satisfactory overall clinical outcomes. However, it resulted in a relatively high incidence of mild to severe anemia and increased burden for the program and the patients.     

Hematological effects of zidovudine prophylaxis in newborn infants with and without prenatal exposure to zidovudine

Postnatal prophylaxis with oral zidovudine (ZDV) is associated with hematological effects. However, it is still unknown whether selection of non-ZDV-based regimens in pregnancy may reduce hematological toxicity associated with postnatal ZDV prophylaxis. The aim of this study was to define the hematological effects of ZDV prophylaxis in newborns with and without prenatal exposure to ZDV. Sixty-five newborns from mothers infected with HIV who, during pregnancy, received HAART regimens with (n:44) and without (n:21) ZDV were evaluated. Virological and hematological data were compared at birth and at 4 weeks and 6 months of life. Newborns with prenatal ZDV exposure had significantly worse hematological values at birth, with lower levels of hemoglobin (14.3 g/dl vs. 16.2 g/dl, P=0.001), red blood cell count (3.45 × 10(6) cells/mm(3) vs. 4.48 × 10(6) cells/mm(3), P<0.001), and hematocrit (41.0% vs. 46.8%, P<0.001), and higher values of mean corpuscular volume (119 fl vs. 103 fl, P<0.001). The start of ZDV prophylaxis determined significantly greater adverse hematological changes in newborns without prenatal ZDV exposure, and at 4 weeks and 6 months of life the two groups had substantially identical hematological values. The selection of non-ZDV-based regimens in pregnancy does not reduce the final hematological effects of postnatal ZDV at 4 weeks and at 6 months of life. However, two distinct pathways may be observed: newborns exposed prenatally to ZDV have worse hematological values at birth, while newborns without prenatal ZDV exposure have particularly marked postnatal effects. The distinct effects of these two pathways should be considered.     

Prevention of mother-to-child transmission of HIV in Thailand: physicians' attitudes on zidovudine use, pregnancy termination, and willingness to provide care.

We administered a survey to Thai physicians, using regular mail, on their attitudes and practices regarding zidovudine (ZDV) use and pregnancy termination in HIV-infected pregnant women. We surveyed their willingness to care for these patients as well. In 1997, 79.5% of 480 respondents reported that they did not routinely use perinatal ZDV prophylaxis. Predictors of failure to use ZDV found to be significant in our logistic regression model included practice outside of Bangkok (odds ratio [OR] = 2.0), belief that ZDV is not cost effective (OR = 2.5), unfamiliarity with AIDS Clinical Trials Group (ACTG) 076 results (OR = 2.5), and failure to screen for HIV routinely (OR = 4.9). Elective abortion for HIV-infected women was advocated by 45.3% of respondents. Factors associated in multivariable analysis with this preference included specialty training in obstetrics/gynecology (OR = 1.8), practice inside Bangkok (OR = 2.0), male gender (OR = 1.9), and treatment of < or =2 HIV-infected patients yearly (OR = 1.8). A significant proportion of respondents described themselves as unwilling to perform pelvic examinations (19.2%), vaginal deliveries (30.7%), or cesarean deliveries (39.5%) on women who were known to be infected with HIV. We conclude that many Thai obstetric providers are reluctant to care for HIV-infected women, do not routinely use perinatal ZDV prophylaxis, and prefer to terminate pregnancies among HIV-infected patients. Physician education concerning the value of HIV screening and antiretroviral therapy in HIV-infected pregnant women is needed urgently in Thailand.     

Combination antiretroviral strategies for the treatment of pregnant HIV-1-infected women and prevention of perinatal HIV-1 transmission

CONTEXT: The Women and Infants Transmission Study is a prospective natural history study that has been enrolling HIV-1-infected pregnant women and their infants since 1989. OBJECTIVE: To evaluate the impact of different antiretroviral regimens on perinatal HIV-1 transmission at the population level. DESIGN: Prospective cohort study. Plasma HIV-1 RNA levels were serially measured in 1542 HIV-1-infected women with singleton live births between January 1990 and June 2000. MAIN OUTCOME MEASURE: HIV-1 status of the infant. RESULTS: HIV-1 transmission was 20.0% (95% confidence interval [CI], 16.1%-23.9%) for 396 women who not receiving prenatal antiretroviral therapy; 10.4% (95% CI, 8.2%-12.6%) for 710 receiving zidovudine monotherapy; 3.8% (95% CI, 1.1%-6.5%) for 186 receiving dual antiretroviral therapy with no or one highly active drug (Multi-ART); and 1.2% (95% CI, 0-2.5%) for 250 receiving highly active antiretroviral therapy (HAART). Transmission also varied by maternal delivery HIV RNA level: 1.0% for <400; 5.3% for 400 to 3499; 9.3% for 3500 to 9999; 14.7% for 10,000 to 29,999; and 23.4% for >30,000 copies/mL (p =.0001 for trend). The odds of transmission increased 2.4-fold (95% CI, 1.7-3.5) for every log10 increase in delivery viral load. In multivariate analyses adjusting for maternal viral load, duration of therapy, and other factors, the odds ratio for transmission for women receiving Multi-ART and HAART compared with those receiving ZDV monotherapy was 0.30 (95% CI, 0.09-1.02) and 0.27 (95% CI, 0.08-0.94), respectively. CONCLUSION: Levels of HIV-1 RNA at delivery and prenatal antiretroviral therapy were independently associated with transmission. The protective effect of therapy increased with the complexity and duration of the regimen. HAART was associated with the lowest rates of transmission.     

Exposure to antiretroviral therapy in utero or early life: the health of uninfected children born to HIV-infected women

Concerns have been raised over possible adverse effects of prophylactic antiretroviral therapy (ART) on the fetus and newborn. We analyzed data relating to uninfected children enrolled in the European Collaborative Study and investigated the association between ART exposure, perinatal problems, and major adverse health events later in life. Median length of follow-up was 2.2 (0-15.9) years. Of the 2414 uninfected children, 687 (28%) were exposed to ART in all three periods (antenatal, intrapartum, and neonatal). Of the 1008 infants exposed to ART at any time, 906 (90%) were exposed antenatally, 840 (83%) neonatally, and 750 (74%) both antenatally and neonatally. ART exposure was not significantly associated with pattern or prevalence of congenital abnormalities or low birth weight. In multivariate analysis, prematurity was associated with exposure to combination therapy without a protease inhibitor (PI) (OR = 2.66; 95% CI: 1.52-4.67) and with a PI (OR = 4.14; 95% CI: 2.36-7.23). ART exposure was associated with anemia in early life ( <.001). There was no evidence of an association with clinical manifestations suggestive of mitochondrial abnormalities. The absence of serious adverse events in this large cohort of uninfected children exposed to prophylactic ART in the short to medium term is reassuring.     

Range of normal neutrophil counts in healthy zimbabwean infants: implications for monitoring antiretroviral drug toxicity

Mother-to-child HIV prevention trials in sub-Saharan Africa use the US National Institutes of Health Division of AIDS (DAIDS) grading scale to monitor hematologic toxicity. A recent study of nevirapine prophylaxis given for 6 months in breast-feeding Zimbabwean infants reported several cases of relative neutropenia in clinically well infants, raising concerns of drug toxicity. However, the DAIDS tables are based on normal blood counts for white infants, although there is evidence that black African infants may have lower absolute neutrophil counts (ANCs) than white infants. To establish normal hematologic values in black Zimbabwean infants and to quantify the apparent prevalence of relative neutropenia in this population, we evaluated HIV-uninfected healthy infants born to HIV-uninfected women at birth, 10 days, 6 weeks, 3, and 4 months of life. A physical examination and blood count were performed at each visit, and an HIV test was performed at the final visit. The ANC values were graded using the DAIDS table. A total of 145 healthy term infants satisfied the inclusion criteria. The mean ANC values for Zimbabwean infants were less than half of the corresponding standard values at all 5 time points (P < 0.0001). Using the DAIDS table in use at the time that the blood was collected, 57% of these healthy infants had relative neutropenia of any grade at birth, followed by 29% at day 10, 53% at 6 weeks, 32% at 3 months, and 37% at 4 months of life. Our data indicate that relative neutropenia exists in healthy black Zimbabwean infants. The guidelines for identifying toxicity were changed in December 2004. However, even by the new DAIDS tables, 43%, 23%, 24%, 42%, and 43% of these healthy babies had relative neutropenia at the time of the 5 visits. Future HIV prevention and treatment trials in sub-Saharan Africa should use normal hematologic values derived from African infants to avoid the overestimation of antiretroviral drug toxicity.     

Effect of prenatal zidovudine on disease progression in perinatally HIV-1-infected infants

OBJECTIVE: To determine the influence of prenatal zidovudine (ZDV) prophylaxis on the course of HIV- 1 infection in children by comparing the clinical outcome of infants born to HIV- 1-seropositive mothers who did versus those who did not receive ZDV during pregnancy. METHODS: Medical records of HIV-1-seropositive mothers and their infants were reviewed retrospectively. Participants were divided according to maternal ZDV use: no ZDV (n = 152); ZDV (n = 139). The main outcome measure was rapid disease progression (RPD) in the infant, defined as occurrence of a category C disease or AIDS-related death before 18 months of age. RESULTS: HIV vertical transmission rates were significantly different (no ZDV versus ZDV: 22.3% versus 12.2%; p = .034). Among infected infants, the RPD rate was 29.4% in the no ZDV group compared with 70.6% in the ZDV group (p = .012), and prematurity was significantly associated with a higher risk of RPD (p = .027). CONCLUSIONS: The rate of RPD was significantly higher among perinatally infected infants born to HIV-infected mothers treated with ZDV than among infected infants born to untreated mothers. The decreased proportion of infected infants with nonrapid disease progression in the former group might be related to the ability of ZDV to block intrapartum transmission preferentially and also to nonrapid disease progression resulting from intrapartum transmission.     

Pregnancy outcomes in HIV-infected and uninfected women in rural and urban South Africa

OBJECTIVE: To describe pregnancy outcomes among clade C HIV-infected and uninfected women in South Africa. DESIGN: A longitudinal cohort study. METHODS: Pregnant women attending 9 rural/urban antenatal clinics were prospectively recruited and followed up. Women were seen at the clinic or at home after delivery on 4 occasions after enrollment: 2 times within the first 2 weeks of the newborn's life at home, and every 2 weeks thereafter until their first health clinic visit when the infant was 6 weeks old. RESULTS: A total of 3465 women were enrolled; 615 withdrew after delivery, moved away, or had a missing or indeterminate HIV status, leaving 2850 women (1449 HIV-infected women). Six women died after delivery and there were 17 spontaneous abortions and 104 stillbirths. An adverse pregnancy outcome was independently associated with HIV infection (adjusted odds ratio [AOR] = 1.63; P = 0.015), urban enrollment (AOR = 0.39; P = 0.020), and nonhospital delivery (AOR = 13.63; P < 0.001) as well as with a CD4 count <200 cells/mL among HIV-infected women (AOR = 1.86; P = 0.127). Among 2529 singleton liveborn babies, birth weight was inversely associated with maternal HIV (AOR = 1.45; P = 0.02) and maternal middle upper arm circumference (AOR = 0.93; P < 0.001). Early infant mortality was not significantly associated with maternal HIV (hazard ratio [HR] = 1.18; P = 0.52) but was with urban sites (HR = 0.34; P = 0.045). Low birth weight substantially increased mortality (AOR = 8.3; P < 0.001). HIV status of infants by 8 weeks of age (14.6%, 95% confidence interval: 12.5% to 17.0%) was inversely associated with maternal CD4 cell count and birth weight. CONCLUSIONS: HIV-infected women are at a significantly increased risk of adverse pregnancy outcomes. Low-birth-weight infants of HIV-infected and uninfected women are at substantially increased risk of dying.     

Effects of depression and selective serotonin reuptake inhibitor use on adherence to highly active antiretroviral therapy and on clinical outcomes in HIV-infected patients

OBJECTIVES: To determine the impact of depression on highly active antiretroviral therapy (HAART) adherence and clinical measures and investigate if selective serotonin reuptake inhibitors (SSRIs) improve these measures. DESIGN: Retrospective cohort study. METHODS: In 2 large health maintenance organizations, we measured the effects of depression (with and without SSRI use) on adherence and changes in viral and immunologic control among HIV-infected patients starting a new HAART regimen. HAART adherence, HIV RNA levels, and changes in CD4 T-cell counts through 12 months were measured. RESULTS: A total of 3359 patients were evaluated; 42% had a depression diagnosis, and 15% used SSRIs during HAART. Depression without SSRI use was associated with significantly decreased odds of achieving > or =90% adherence to HAART (odds ratio [OR] = 0.81, 95% confidence interval [CI]: 0.70 to 0.98; P = 0.03). Depression was associated with significantly lower odds of an HIV RNA level <500 copies/mL (OR = 0.77, 95% CI: 0.62 to 0.95; P = 0.02). Depressed patients compliant with SSRI medication (>80% adherence to SSRI) had HAART adherence and viral control statistically similar to nondepressed HIV-infected patients taking HAART. Comparing depressed with nondepressed HIV-infected patients, CD4 T-cell responses were statistically similar; among depressed patients, those compliant with SSRI had statistically greater increases in CD4 cell responses. CONCLUSIONS: Depression significantly worsens HAART adherence and HIV viral control. Compliant SSRI use is associated with improved HIV adherence and laboratory parameters.     

Discordant immunologic and virologic responses to highly active antiretroviral therapy are associated with increased mortality and poor adherence to therapy

OBJECTIVE: To examine the independent association of discordant virologic and immunologic responses to highly active antiretroviral therapy (HAART) with mortality. METHODS: A population-based study of 1527 treatment-naive individuals initiating HAART used Cox proportional hazards modeling to determine the independent association of treatment response at 3 to 9 months with nonaccidental mortality. Logistic regression was used to examine associations with discordant responses. RESULTS: Viral load (VL)/CD4 discordant responses were seen in 235 (15.4%) of subjects, and VL/CD4 responses were seen in 179 (11.7%) of subjects. In adjusted Cox regression models, discordant responses were found to be independently associated with an increased risk of mortality (VL/CD4: relative hazard [RH] = 1.87, 95% confidence interval [CI]: 1.15 to 3.04; VL/CD4: RH = 2.47, 95% CI: 1.54 to 3.95). VL/CD4 discordance was found to be associated with increasing age, baseline HIV RNA load <100,000 copies/mL, baseline CD4 counts <50 cells/muL, the use of lamivudine (3TC)/zidovudine (ZDV), and poor adherence to therapy. VL/CD4 discordance was associated with younger age; injection drug use; baseline HIV RNA load >100,000 copies/mL; the use of 3TC/ZDV, didanosine (ddI)/3TC, or ddI/stavudine; and poor adherence to therapy. CONCLUSION: Discordant responses are independently associated with an increased risk of mortality and are, in turn, associated with poor adherence to therapy.     

Advances in the prevention of mother-to-child transmission of HIV-1 infection in resource-limited settings

Ten years after the first trials demonstrating the efficacy of zidovudine (ZDV) for the prevention of mother-to-child transmission (pMTCT) of HIV, different antiretroviral approaches have been validated in resource-limited settings. Remarkable progress has been made in the last 4 years, with trials demonstrating the efficacy of postexposure antiretroviral prophylaxis in Malawi, as well as studies in Thailand and C?te d'Ivoire assessing the efficacy and viral resistance patterns of short-course regimens combining ZDV plus single-dose nevirapine (sdNVP). The field efficacy of a short course of ZDV plus lamivudine (3TC), together with sdNVP, has also been recently reported, with 6-week transmission rates below 5% for the first time in Africa in a population in which 40% breast-feed. The introduction of HAART for pregnant women has begun on a small scale in resource-limited settings and will hopefully further reduce transmission. What remains is the crucial issue of viral resistance after antiretroviral therapy for pMTCT, especially in the context of the growing availability and use of sdNVP in national pMTCT programs. Preliminary data from South Africa and C?te d'Ivoire suggest that the maternal use of ZDV plus 3TC for at least 3 days postpartum may reduce the occurrence of resistance mutations after maternal exposure to sdNVP. In the context of increasing controversy surrounding the use of sdNVP for pMTCT, the World Health Organization has recently reiterate its recommendations for its use for pMTCT in resource-constrained settings within a wide panel of antiretroviral regimens, in order to allow greater and quicker population coverage. The field application of pMTCT study results is a real challenge, and innovative approaches need to be designed an evaluated ot increase uptake of pMTCT programs in resource-poor settings. Research must continue to identify new interventions and new antiretroviral drugs for pMTCT.     

Quantitative RNA testing for diagnosis of HIV-infected infants

Quantitative HIV RNA testing was used for diagnosis in 156 HIV-exposed non-breast-fed infants at less than 6 months of age (54 infected, 102 uninfected) enrolled in the Perinatal AIDS Collaborative Transmission Study. Sensitivity was 29% in the first week, 79% at 8 to 28 days of age, and >90% at 29 days of age and thereafter; specificity was 100% in all periods, except at 29 to 60 days of age, when specificity was 93%. Neither sensitivity nor specificity was significantly affected by maternal or infant zidovudine (ZDV) treatment, even though infant viral loads were lower during the first 6 weeks in infants who received perinatal ZDV prophylaxis ( p=.005). Paired analysis of DNA and RNA measurements revealed no advantage for either test. Quantitative RNA testing can be used for diagnosis in HIV-exposed infants, recognizing the chance for a false-positive test result. It may be most useful as a confirmatory test in infants with another positive diagnostic test result.     

Field evaluation of the efficacy and immunogenicity of recombinant hepatitis B vaccine without HBIG in newborn Vietnamese infants

A study involving more than 2,000 infants was conducted in Vietnam to assess the field effectiveness and immunogenicity of recombinant hepatitis B vaccine given at birth, 1 month, 2 months, without concomitant hepatitis B immune globulin (HBIG). All received a 5 microg dose of H-B-VAX II at birth. Infants born to non-carrier mothers (Group 1; N = 1798) then received 2.5 microg doses at 1 and 2 months of age, while infants of HBeAg-negative (Group 2; N = 125) or HBeAg-positive (Group 3; N = 88) carrier mothers received 5 microg doses. No Group 1 or 2 vaccinees were infected. In Group 3, 12 (14.6%) of 82 infants did become infected (estimated efficacy 84%). 98.0-98.6% of uninfected infants who were tested for anti-HBs developed a seroprotective concentration > or = 10 IU/L. In hyperendemic Vietnam, where routine maternal screening and passive-active prophylaxis of high-risk infants with vaccine plus HBIG is not feasible, administration of vaccine alone to all newborns may control effectively HBV infection.