Wasting during pregnancy increases the risk of mother-to-child HIV-1 transmission

OBJECTIVES: To examine whether wasting during pregnancy, as measured by weight loss and low weight gain, is associated with increased mother-to-child transmission (MTCT) of HIV-1. METHODS: This was a cohort study in Dar es Salaam, Tanzania, among 957 HIV-1-infected pregnant women. Weight was measured at the first prenatal visit and every month thereafter until delivery. Weight loss was defined as a weekly rate of weight gain 0 and /=167 g/wk, weight loss during pregnancy was related to higher risk of intrauterine MTCT (adjusted relative risk [RR] = 2.32, 95% CI = 1.23-4.36, P = 0.009), HIV positive at birth or fetal death (RR = 2.13, 95% CI = 1.40-3.24, P = 0.0004), and HIV positive at birth or early neonatal death (RR = 1.96, 95% CI = 1.26-3.07, P = 0.003). The rate of weight gain during the 3rd trimester was inversely related to the risk of intrapartum/early breast-feeding transmission (adjusted P value, test for trend = 0.05). CONCLUSIONS: Weight loss during pregnancy increases the risk of early MTCT. Identifying causes of wasting during pregnancy may provide clues for new strategies to prevent MTCT.     

Estimating the time of HTLV-I infection following mother-to-child transmission in a breast-feeding population in Jamaica.

Mother-to-child transmission of human T-cell lymphotropic virus type I (HTLV-I) is primarily due to prolonged breast-feeding (>6 months) in the postnatal period. Most infant infections are not identifiable until 12 to 18 months of age by available whole virus Western blot serologic tests because of their inability to distinguish passively transferred maternal antibody from infant antibody. We investigated two methods to assess more accurately the time of infant infection. In prospectively collected serial biospecimens, HTLV-I-specific immunoglobulin (Ig) isotypes of IgM and IgA were determined by Western blot and HTLV-I proviral DNA was detected by polymerase chain reaction (PCR). IgA and IgG reactivity was assessed in periodic serum samples from 16 HTLV-I-seropositive children while IgM reactivity was assessed in 9 of the 16 children. Approximately three to five samples were tested for each child. IgG reactivity was observed in 100% of children at 24 months of age and 73% of children at 6-12 months of age; however, this could represent maternal and not infant antibody. Both IgA and IgM reactivity were insensitive indicators of infection, with only 50% of children showing reactivity at 24 months of age. PCR testing was performed in biospecimens obtained from 11 of these children. An estimated median time of infection of 11.9 months was determined by PCR, which was similar to the median time to infection determined by whole virus Western blot (12.4 months; P = 0.72). PCR tests support a median time to infection that is similar to that estimated by whole virus Western blot.     

Immunoprophylaxis to prevent mother-to-child transmission of HIV-1

Antiretroviral therapy can profoundly reduce the risk of mother-to-child transmission (MTCT) of HIV, but the drugs have a relatively short half-life and should thus be administered throughout breast-feeding to optimally prevent postnatal infection of the infant. The potential toxicities and the development of resistance may limit the long-term efficacy of antiretroviral prophylaxis, and a safe and effective active/passive immunoprophylaxis regimen, begun at birth, and potentially overlapping with interpartum or neonatal chemoprophylaxis, would pose an attractive alternative. This review draws on data presented at the Ghent Workshop on prevention of breast milk transmission and on selected issues from a workshop specifically relating to immunoprophylaxis held in Seattle in October 2002. This purpose of this review is to address the scientific rationale for the development of passive (antibody) and active (vaccine) immunization strategies for prevention of MTCT. Data regarding currently or imminently available passive and active immunoprophylaxis products are reviewed for their potential use in neonatal trials within the coming 1-2 years.     

Predictive value of HIV-1 viral load on risk for opportunistic infection

OBJECTIVE: The relationship between HIV-1 viral load and the risk for opportunistic infection (OI) was examined in Adult AIDS Clinical Trial Group (AACTG) 722, a virology substudy of AACTG 323: a phase 4 randomized study designed to examine the use of chronic suppressive versus episodic fluconazole therapy. METHODS: The primary analysis used a case-control sampling scheme with two controls per "case" (subjects that developed an OI) matched by gender, age, and time on study. Forty-five cases and matched controls were identified and used in the analysis. RESULTS: Study 722 accrued 518 subjects between 5/97 and 11/99. Forty-five subjects developed serious OIs or refractory candidiasis. Median baseline CD4 count was 24 cell/mm3 for cases and 46 for controls (p =.003). Median viral load (VL) was 5.02 log10 copies/mL for cases and 4.08 for controls (p =.002). Multivariate analysis found four independent variables associated with time to OI: baseline VL and CD4 (RR = 2.2 per log increment and 6.0 per 50-cell increment, respectively), a one log increase in VL at any time (RR = 15), and history of an OI (RR = 5.2). CONCLUSIONS: VL and changes in VL were independently associated with risk of development of OIs in a prospective study and should be considered by clinicians when assessing patients for risk of OI.     

Male viral load and heterosexual transmission of HIV-1 subtype E in northern Thailand

We evaluated the association between HIV-1 RNA copies/mL in men and heterosexual transmission to their female partners among 493 couples in Thailand. Husbands were identified as HIV-positive when they were screened as blood donors; nearly all were infected with HIV subtype E. Wives had no known risks for HIV infection other than sex with their husbands. In multivariate analysis, each log10 increment of HIV RNA in the man was associated with an 81% increased rate of HIV transmission to his wife (odds ratio = 1.81, 95% confidence interval: 1.33-2.48). No transmission occurred at viral loads below 1094 copies/mL, and a dose-response effect was seen with increasing viral load in the man. In multivariate analysis, a history of a sexually transmitted disease in the man or woman, longer duration of hormonal contraceptive use, and the woman's onset of sexual activity at less than 20 years of age were also associated with increased seropositivity of the wife.     

HIV-1 reservoirs in breast milk and challenges to elimination of breast-feeding transmission of HIV-1

By compensating for the relative immaturity of the neonatal immune system, breast milk and breast-feeding prevent deaths in children. Nevertheless, transmission of HIV-1 through breast-feeding is responsible for more than half of new pediatric HIV infections. Recent studies of possible HIV-1 reservoirs in breast milk shed new light on features that influence HIV-1 transmission through breast-feeding. The particular characteristics of breast milk CD4(+) T cells that distinguish them from circulating blood lymphocytes (high frequency of cell activation and expression of memory and mucosal homing markers) facilitate the establishment of HIV-1 replication. Breast milk also contains a plethora of factors with anti-infectious, immunomodulatory, or anti-inflammatory properties that can regulate both viral replication and infant susceptibility. In addition, CD8(+) T lymphocytes, macrophages, and epithelial cells in breast milk can alter the dynamics of HIV-1 transmission. Even during efficient antiretroviral therapy, a residual stable, CD4(+) T cell-associated reservoir of HIV-1 is persistently present in breast milk, a likely source of infection. Only prophylactic treatment in infants--ideally with a long-acting drug, administered for the entire duration of breast-feeding--is likely to protect HIV-exposed babies against all forms of HIV transmission from breast milk, including cell-to-cell viral transfer.     

Maternal viral load,CD4 cell count and vertical transmission of HIV-1

HIV load and CD4 cell numbers were measured among 95 HIV infected women during pregnancy in order to determine their value as prognostic markers for transmission of virus from mother to infant. Among the 94 live births, 13 children were infected with HIV, 69 were uninfected and 12 were of unknown infection status. HIV RNA levels, as measured by nucleic acid sequence based amplification, were significantly higher (P < 0.001) in women who transmitted virus than among those who did not transmit and maternal viral load was a stronger predictor of transmission than CD4 cell number. The predicted rate of transmission relative to maternal HIV RNA was 2% at 1,000 copies, 11% at 10,000 copies and 40% at 100,000 copies/ml. Little variation in viral load occurred during pregnancy and there was an association between viral load and prematurity, the mean gestation at delivery decreasing by 1.3 weeks for every 10-fold increase in maternal HIV RNA (P = 0.007). This study demonstrates that a high level of maternal HIV RNA is a risk factor for transmission of virus to the infant and maternal viral load is of more value as a prognostic marker for transmission risk than CD4 cell number. High viral load is also associated with premature delivery. Maternal viral load is therefore a useful marker on which to base management decisions during pregnancy. J. Med. Virol. 54:113–117, 1998. © 1998 Wiley-Liss,Inc.     

Subclinical mastitis, cell-associated HIV-1 shedding in breast milk, and breast-feeding transmission of HIV-1

BACKGROUND: Mastitis has been identified as a risk factor for mother-to-child transmission (MTCT) of HIV-1 through breast-feeding. It is unclear whether this association is mediated by increased cell-free virus (CFV) versus cell-associated virus (CAV) HIV shedding in breast milk. METHODS: We examined the risk of MTCT associated with subclinical mastitis and the relation between mastitis and CFV or CAV shedding in breast milk. Fifty-nine women who transmitted HIV through breast-feeding (cases) were individually matched to 59 nontransmitting controls nested in a cohort from Tanzania. For each case, we selected a milk specimen obtained before the infant's first positive test to quantify sodium (Na) and potassium (K) and measure CFV and CAV concentrations. Controls were matched on the child's age at the time of sample collection. RESULTS: Women with a breast milk Na/K ratio suggestive of mastitis (>1.0) had an 11-fold greater odds of transmission (95% confidence interval [CI]: 1.2 to 98.1), compared to women with a Na/K 相似文献   

CCR5, RANTES and SDF-1 polymorphisms and mother-to-child HIV-1 transmission

Among 288 HIV-1-infected, breastfeeding women who received zidovudine prophylaxis and were followed with their infants in Nairobi, we found no associations between maternal genetic polymorphisms in CCR5 (59029G/A, 59353T/C, 59356T/C, 59402G/A), RANTES (-403G/A) and SDF-1 (3’801G/A) and mother-to-child HIV-1 transmission; plasma, cervical and breastmilk viral loads; or breastmilk chemokine concentrations.     

Selenium status, pregnancy outcomes, and mother-to-child transmission of HIV-1

BACKGROUND: Among HIV-infected pregnant women, low selenium status may increase risk of mother-to-child transmission (MTCT) of HIV and poor pregnancy outcomes (low birthweight, small for gestational age, preterm birth, and fetal death) through several mechanisms, such as by promoting maternal HIV disease progression, viral shedding in the genital tract, and development of mastitis. However, there is no direct epidemiologic evidence on these relations among HIV-infected pregnant women. OBJECTIVE: To investigate the association between selenium status during pregnancy and pregnancy outcomes, MTCT of HIV, and child mortality. DESIGN: Baseline plasma selenium measurements from HIV-positive pregnant women (n = 670) were obtained between 12-27 weeks of gestation and mother-child pairs were followed prospectively until 24 months after delivery. RESULTS: Low plasma selenium levels were associated with increased risks of fetal death, child death, and HIV transmission through the intrapartum route. Low selenium status was not associated with risks of low birthweight or preterm birth but was associated with an apparently lower risk of small for gestational age. CONCLUSION: Adequate selenium status may be beneficial for some but not all pregnancy outcomes. Further studies are needed to better understand the role of selenium status in pregnancy outcomes, HIV transmission, and child health.     

Diversity of the HIV-1 long terminal repeat following mother-to-child transmission

A study of the human immunodeficiency virus Type 1 (HIV-1) 5' long terminal repeat (LTR) was performed to determine the extent of variation found within the LTR from 19 mother-infant pairs in Tanzania and to assess whether the LTR is useful in distinguishing maternal sequences that were transmitted to infants. HIV-1 subtypes A, C, and D as well as intersubtype recombinant LTR sequences were detected in mothers and infants. The LTR subtype was 100% concordant between mothers and their infants. Diversity calculations showed a significant reduction in LTR variation in infants compared to their mothers. However, the overall magnitude of LTR variation was less than that found in the env gene from the same individuals. These data suggest a selective constraint active upon the 5' long terminal repeat that is distinct from immune selective pressure(s) directed against HIV-1 structural genes. Detection of maternal LTR variants that were transmitted to infants may yield important information concerning nonstructural determinants of HIV-1 transmission from mother to infant.     

Course of viral load throughout HIV-1 infection

HIV-1 RNA levels are routinely monitored as part of patient management. However, little is known about the course of HIV-1 RNA levels over the entire period of infection. The aim of this study was to investigate the course of HIV-1 RNA levels in a cohort of men with hemophilia who were observed for up to 17 years after HIV-1 seroconversion, and to assess the risk of HIV disease progression at any HIV-1 RNA level. Viral loads were measured on annual stored serum samples in 107 men with hemophilia A using the Roche Amplicor Monitor assay with non-B primers. On average, HIV-1 RNA levels increased significantly by 0.11 log10 per year over the course of HIV infection. This rate of increase was significantly faster in those who developed AIDS or died over the subsequent 12 to 17 year period, and in those who were older at HIV- 1 seroconversion. The risk of developing AIDS and death remained low when the HIV-1 RNA level was below 4 log10 copies/ml, but increased rapidly thereafter, supporting current guidelines for the initiation of antiretroviral therapy after the viral load has exceeded this level.     

Heterosexual transmission of HIV-1 is associated with high plasma viral load levels and a positive viral isolation in the infected partner.

Risk factors for heterosexual HIV transmission are not fully understood. In fact, a proportion of people with sexual exposure to HIV remain uninfected despite multiple and continuous intercourse with HIV-infected partners. In this work, we have analyzed those virologic parameters potentially involved in the transmission of HIV through heterosexual contact. Thirty-eight couples with continuous unprotected sexual intercourse were included. HIV transmission occurred in 10 of 38 couples. No differences in clinical characteristics, exposure time, sexual practices, CD4 counts, or polymorphism in CCR5 were found between transmitter and nontransmitter groups. In contrast, virologic data were different between both groups; median values of viral load were 21.139 and 5.484 RNA copies/ml of plasma in the transmitter and nontransmitter groups, respectively, and a significant difference was found in mean viral load values (p = .03, Mann-Whitney test). Viral isolation was obtained in 90% of transmitters, but in only 44% of nontransmitter subjects (p = .02, Fisher's exact test). These data show that viral load levels and a positive viral isolation in culture must be considered as risk factors for heterosexual transmission of HIV-1.     

HIV-1 co-receptor usage: influence on mother-to-child transmission and pediatric infection

Viral CCR5 usage is not a predictive marker of mother to child transmission (MTCT) of HIV-1. CXCR4-using viral variants are little represented in pregnant women, have an increased although not significant risk of transmission and can be eventually also detected in the neonates. Genetic polymorphisms are more frequently of relevance in the child than in the mother. However, specific tissues as the placenta or the intestine, which are involved in the prevalent routes of infection in MTCT, may play an important role of selective barriers. The virus phenotype of the infected children, like that of adults, can evolve from R5 to CXCR4-using phenotype or remain R5 despite clinical progression to overt immune deficiency. The refined classification of R5 viruses into R5(narrow) and R5(broad) resolves the enigma of the R5 phenotype being associated with the state of immune deficiency. Studies are needed to address more in specific the relevance of these factors in HIV-1 MTCT and pediatric infection of non-B subtypes.     

NucliSens HIV-1 QT和Amplicor HIV-1 monitor1.5方法测定HIV-1病毒载量的比较研究

目的进行NuchSens HIV-1 QT和Amplicor HIV-1 monitor 1．5检测相同临床样品HIV-1病毒载量值之间的比较研究。方法收集临床样本82份，使用两种方法测定病毒载量，对病毒载量值进行统计分析。结果未测到核酸的和两种方法病毒载量对数值之差小于0．5的占88．9％；用△log10 VL〈0．5的56份样本统计两种方法的相关性，相关系数为0．956。结论NucliSens HIV-1 QT和Amphcor HIV-1 monitor 1．5两种方法测定的HIV病毒载量值有很好的相关性。     

一种简易的HIV-1病毒载量定量筛查方法的建立

目的 建立一种基于RT-PCR法的简易的HIV-1感染者或艾滋病患者血浆病毒载量筛查方法.方法 在广西南宁市采集18例HIV-1感染者和18例阴性对照者血液标本,提取RNA,以引物LTR-1/LTR-2对待测样本进行PCR扩增,获得Ct值.同时,应用Nuclisens EasyQ HIV-1 v1.2法作为对照对这些样本进行病毒载量检测.对Ct值与病毒载量之间进行相关性分析,获得相应的回归方程.结果 待测样本中HIV-1感染者Ct值在29.103～31.610个循环之间,阴性对照者未能扩增出产物.RT-PCR法Ct值与Nuclisens EasyQ HIV-1 v1.2法检测出的病毒载量对数值之间具有良好的线性关系（r=-0.51,P=0.03）,回归方程为logY（viral road）=57.55-1.56＆#215;（Ct value）.结论 所建立的HIV-1病毒载量RT-PCR检测方法操作简单,价格便宜,与商业化试剂盒具有较好的一致性,可用于HIV-1感染定量筛查.