Lactic acidemia in human immunodeficiency virus-uninfected infants exposed to perinatal antiretroviral therapy

OBJECTIVE: To investigate potential mitochondrial toxicity in HIV-uninfected infants exposed to highly active antiretroviral therapy (HAART) in utero and/or neonatal zidovudine. DESIGN: A prospective observational study performed in a tertiary referral center for HIV-infected women and their infants and children. METHODS: Plasma lactate was measured repeatedly during the first 6 months of life in a consecutive cohort of infants exposed to HAART in utero and/or neonatal zidovudine. Maternal CD4, HIV RNA concentration, antiretroviral and substance use histories, mode of delivery, infant gender, cord pH, Apgar score and birth weight were collected. RESULTS: The plasma lactate was above normal on at least 1 occasion in 35 of 38 (92%) infants and reached levels > or =5 mmol/l in 10 (26%) infants. Overall 78 of 117 (68%) lactate measurements were elevated, with 11 (10%) in the serious (> or =5 mmol/l) range. None of the infants received antiretrovirals beyond 6 weeks, yet elevated lactates persisted up to age 6 months. Two infants had reversible symptoms consistent with those of lactic acidemia. No association was found between the infant peak lactate and the type of therapy during pregnancy, its duration or maternal substance use. CONCLUSION: Transient lactic acidemia was observed in the majority of HIV uninfected infants exposed to HAART in utero and/or zidovudine neonatally. We hypothesize that the hyperlactatemia is a consequence of persistent, primarily subclinical, mitochondrial toxicity from the transplacental and neonatal exposure to antiretrovirals and of impaired hepatic lactate clearance. Although the clinical relevance of our findings is unknown, we recommend lactate monitoring in these infants, considering discontinuation of neonatal zidovudine in symptomatic infants with lactate > or =5 mmol/l and careful long term follow up of these children.     

Missed opportunities for prevention of mother-to-child transmission of human immunodeficiency virus type 1 in Latin America and the Caribbean: the NISDI perinatal study

Cases of mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV-1) in a prospective cohort study in Latin America and the Caribbean were analyzed. Eight of 820 eligible infants became infected [transmission rate, 0.98% (95% CI = 0.45-1.96%)]. Five cases (62%) represented missed opportunities for prevention of MTCT of HIV-1, suggesting the need for ongoing training and education of clinicians regarding prevention of MTCT of HIV-1.     

Reduction in perinatal transmission and mortality from human immunodeficiency virus after intervention with zidovudine in Barbados

OBJECTIVES: To evaluate the impact of zidovudine (ZDV) intervention on vertical transmission and HIV-related mortality in two groups of pregnant mothers and their respective infants. METHODS: A modified long course Paediatric AIDS Clinical Trial Group 076 protocol was used. None of the infants was breast-fed. Maternal CD4 T lymphocyte counts and viral loads were not monitored. Infants were followed for clinical progress, and serial serologic testing was performed to the age of 24 months, or until two successive HIV (enzyme-linked immunosorbent assay) tests were negative. In a historically case-controlled prospective study, the transmission rate in ZDV-untreated mother-infant pairs in which infants were born during 1991 through 1995 was compared with the transmission rate in ZDV-treated mother-infant pairs in which infants were born between 1996 and 2000. RESULTS: In the 151 HIV-seropositive pregnant women and their 153 infants studied (2 pairs of twins), 93 mother-infant pairs were treated, and 59 were untreated (control group). Vertical transmission occurred in 5.5% [95% confidence interval (95% CI) 1.9 to 12.5] of the treated group of infants and in 27.1% (95% CI 16.7 to 40.5) of the untreated group. There was a 79.7% (95% CI 59.8 to 92.1%) relative reduction risk of transmission, which was statistically significant (z =3.18, two tailed P= 0.0001). Three infant deaths (3.7%) were recorded in the untreated group, and 1(1%) death was recorded in the treated group. In ZDV-untreated infants, deaths occurred at age <1 year, resulting from respiratory complications. One ZDV-treated infant died at 4 years of age with Pneumocystis carinii pneumonia. CONCLUSIONS: Our study demonstrated a statistically significant reduction in the vertical transmission of HIV after intervention with ZDV therapy.     

Low-dose zidovudine in children with an human immunodeficiency virus type 1 infection acquired in the perinatal period

This report describes the one-year results of a noncomparative study designed to assess the safety and tolerance of low-dose zidovudine (azidothymidine) given orally to 60 human immunodeficiency virus type 1-infected infants and children. At baseline, the mean age was 1.9 years (+/- 1.4), and all were symptomatic: 43% were P2A and 57% were P2B to F according to the Centers for Disease Control classification. All the patients received zidovudine for at least 6 months, and 52 of them (87%) completed a full year of therapy. The mean duration of follow-up was 346 days (+/- 42) (range, 183 to 366 days). The initial therapy consisted of four daily doses of 100 mg/m2 (400 mg/m2 per day, equivalent to 20 mg/kg per day). However, this treatment was modified when neutropenia or anemia was observed. Twenty-nine children (48%) remained at the initial therapy for the entire study. Zidovudine dosage was adjusted 92 times in the other 31 children (52%), mostly due to neutropenia (83%). Altogether, the time under full-dose therapy represented 81% of the total duration of the protocol for all patients. Children with mild symptoms, P2A at study entry, were more likely to remain under full-dose therapy than children with severe symptoms, P2B to F: the time under full-dose therapy represented 91% of the duration of the protocol for the former group and only 74% for the latter one (P less than .02). No clinical adverse experiences were attributed directly to zidovudine. Thirty-seven children were prescribed trimethoprim-sulfametoxazole as a prophylaxis for Pneumocystis carinii pneumonia.(ABSTRACT TRUNCATED AT 250 WORDS)     

人类免疫缺陷病毒的母婴传播与预防

自 198 1年美国首次报道艾滋病 (acquiredimmunodefi ciencysyndrome ,AIDS)以来 ,AIDS已给人类带来了巨大灾难。在过去 2 0年内 ,约有 12 0 0万人被AIDS夺去生命 ,其中30 0万为儿童[1] 。据联合国艾滋病控制规划署和世界卫生组织估计 ,至 2 0 0 1年底超过 10 0万儿童感染HIV。     

Serum immunoglobulins in children perinatally exposed to human immunodeficiency virus

OBJECTIVE: Hypergammaglobulinemia is an early manifestation of perinatal HIV infection. Our objective was to analyze the differences in serum immunoglobulin levels between infected and seroreverter children and their association with clinical outcome. METHODS: We carried out a historical prospective study with 107 infected and 90 seroreverter children. We compared the IgA, IgG, and IgM levels between infected and seroreverters in the first 18 months of life; IgA, IgG, and IgM as surrogate markers of infection; and IgA, IgG, and IgM levels in the first 5 years in infected children, according to clinical outcome. The Mann-Whitney test was used for comparison between groups. Surrogate markers were assessed according to sensitivity, specificity, positive and negative predictive values, and J index. RESULTS: Infected children, when compared to seroreverters, showed significantly higher levels of: IgM from the 1st to the 5th trimester; IgA and IgG from the 2nd to the 6th trimester (P /= 90 mg/dl in the 2nd trimester and IgG >/= 1,700 mg/ dl or 1,200 mg/dl in the 2nd and 3rd trimesters were associated with HIV infection with J indexes of 0.97, 0.92, and 0.93, respectively. Infected children in the B and C categories, compared to those in the N and A, showed higher levels of IgM from the 2nd to the 4th year, and IgA from the 3rd to the 5th year (P 相似文献   

Technical report: perinatal human immunodeficiency virus testing and prevention of transmission. Committee on Pediatric Aids

In 1994, the US Public Health Service published guidelines for the use of zidovudine to decrease the risk of perinatal transmission of human immunodeficiency virus (HIV). In 1995, the American Academy of Pediatrics and the US Public Health Service recommended documented, routine HIV education and testing with consent for all pregnant women in the United States. Widespread incorporation of these guidelines into clinical practice has resulted in a dramatic decrease in the rate of perinatal HIV transmission and has contributed to more than a 75% decrease in reported cases of pediatric acquired immunodeficiency syndrome (AIDS) since 1992. Substantial advances have been made in the treatment and monitoring of HIV infection; combination antiretroviral regimens that maximally suppress virus replication are now available. These regimens are recommended for pregnant and nonpregnant individuals who require treatment. Risk factors associated with perinatal HIV transmission are now better understood, and recent results from trials to decrease the rate of mother-to-child HIV transmission have contributed new strategies with established efficacy. However, perinatal HIV transmission still occurs; the Centers for Disease Control and Prevention estimates that 300 to 400 infected infants are born annually. Full implementation of recommendations for universal, routine prenatal HIV testing and evaluation of missed prevention opportunities will be critical to further decrease the incidence of pediatric HIV infection in the United States. This technical report summarizes recent advances in the prevention of perinatal transmission of HIV relevant to screening of pregnant women and their infants.     

Advances in the prevention of vertical transmission of human immunodeficiency virus

The major mode of acquisition of human immunodeficiency virus (HIV) for children is through mother-to-child transmission, which can occur during pregnancy or labor and delivery, or postnatally through breastfeeding. In resource-rich countries, mother-to-child HIV transmission has decreased to less than 2 percent after recommendations for universal prenatal HIV counseling and testing, antiretroviral prophylaxis and elective cesarean delivery, and avoidance of breastfeeding were implemented. In resource-limited settings, effective, shorter, and less expensive antiretroviral prophylaxis interventions also have been identified, but implementation has been slower, and continued transmission through breastfeeding remains a significant problem. This review summarizes recent advances made in prevention of mother-to-child transmission of HIV in the United States and other resource-rich countries, as well as progress in resource-limited countries.     

GB virus C infection in children with perinatal human immunodeficiency virus infection

BACKGROUND: GB virus C (GBV-C) infection occurs in 20-40% of human immunodeficiency virus (HIV)-infected adults, and coinfection is associated with improved HIV disease outcome. METHODS: To determine the prevalence of GBV-C infection in children who were perinatally infected with HIV, we conducted a cross-sectional prevalence survey in a cohort of perinatally infected HIV-positive children selected from a large, multicenter observational protocol. A blood specimen was obtained and tested for GBV-C viremia with the use of a qualitative GBV-C RNA assay and screened for past GBV-C infection with enzyme-linked immunosorbent assay to detect antibodies to the GBV-C envelope protein E2 (E2 Ab). RESULTS: The 354 children who participated in the substudy were relatively healthy, with a median CD4 of 784 cells/mm and median HIV-1 viral load of 1055 copies/mL. The prevalence of GBV-C viremia was 20 of 353 or 5.7% (95% confidence interval, 3.5-8.6%), and the prevalence of E2 Ab was 12 of 354 or 3.4% (95% confidence interval, 1.8-5.8%). GBV-C viremic patients were older than patients without past GBV-C infection (median age, 12.8 years versus 10.7 years). Median CD4 lymphocyte counts were highest in subjects without GBV-C infection and lowest in those with E2 Ab. CONCLUSIONS: GBV-C prevalence rates are lower in children with perinatal HIV infection than those reported for HIV-infected adults. With the exception of evidence that GBV-C viremic children had lower rates of Centers for Disease Control and Prevention HIV disease category C disease before GBV-C testing, we did not find evidence of improved HIV disease outcome in coinfected patients, but the number of HIV/GBV-C-coinfected children was small.     

Trends in interventions to reduce perinatal human immunodeficiency virus type 1 transmission in North Carolina

BACKGROUND: Mother-to-child transmission of HIV has decreased in industrialized countries because of widespread use of antiretroviral therapy (ART) by HIV-infected pregnant women and perhaps to increased use of elective cesarean section. We evaluated changes in the use of ART and mode of delivery among HIV positive pregnant women in North Carolina. METHODS: We reviewed the medical records of HIV-exposed infants born in North Carolina between January 1, 1998, and December 31, 1999, who were tested for HIV DNA. These results were compared with data collected on HIV-exposed infants born from 1993 through 1997. RESULTS: The use of combination ART increased from 1.5% in 1996 to 73% in 1999. The most common ART was zidovudine/lamivudine (39%) followed by zidovudine-lamivudine-nelfinavir (34%), although 34 combinations were used. Elective cesarean sections in the state increased significantly from 16.5% in the first half of 1998 to 49.4% in the second half of 1999. Overall transmission rates declined from 24.5% in 1993 to an average of 10.6% in 1994 to 1996 (41 of 385) and to 3.5% in 1997 to 1999 (15 of 428). CONCLUSIONS: Increased use of combination ART and elective cesarean section was accompanied by consistently low rates of perinatal transmission. However, because perinatal transmission rates were also low among women who used combination therapy and had vaginal deliveries, it is difficult to determine how much additional benefit cesarean section affords. Most HIV transmission occurred among women who lacked prenatal care and did not receive or adhere to ART.     

Prevention of mother-to-child transmission of human T-lymphotropic virus type-I

Human T-cell lymphotropic virus type I (HTLV-I), an etiologic human retrovirus of adult T-cell leukemia/lymphoma (ATLL), causes approximately 60 new cases of ATLL each year in Nagasaki Prefecture; essentially all cases are fatal, and they account for approximately 0.5% of total deaths in the area. The estimated life risk for an HTLV-I carrier to develop ATLL is approximately 5%. The major transmission pathway of HTLV-I peculiarly endemic in the Nagasaki Prefecture was studied. The prevalence of HTLV-I infection in children of carrier mothers (21%) was significantly higher than that in children in the general population in the area (1%) and more than 85% of mothers of carrier children were carriers. The breast milk of carrier mothers contained HTLV-I-infected cells and was infectious for marmoset via oral administration. A retrospective survey of children of carrier mothers showed that the prevalence of carrier children of carrier mothers was 17 (39%) of 44 and 0 (0%) of 10 when they were given breast milk only or formula only, respectively. These data provide a powerful basis for devising an intervention measure to block the endemic cycle of HTLV-I, ie, if carrier mothers refrain from breast-feeding, the incidence of ATLL will be significantly reduced some 50 years later.