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M L Newell

Publications and source records attributed to M L Newell.

At least 19 recordsLinked to original sources
PubMed2003

Management of vertically HIV-infected children in Europe.

AIM: To describe policies for the therapeutic management of vertically HIV-infected children, and to compare these with practice, using children enrolled in a cohort study in the same setting. METHODS: A postal questionnaire survey of clinicians in the paediatric centres of the European Collaborative Study (ECS) was used. Prospective data collected within the ECS on the treatment and clinical status of infected children seen in these centres in 1999-2001 were analysed and compared with the year 2000 policies reported. RESULTS: In 3 of the 10 centres, the policy was routinely to administer antiretroviral therapy (ART) to infants upon confirmation of infection, and in 7 centres initiation of therapy was delayed until specific clinical, virological and immunological criteria were reached. Evidence of disease progression was a reason for treatment modification in all centres; other considerations included adherence problems and side effects. However, practice did not always match policy. For the 84 children with at least 5 y of follow-up (73 treated and 11 untreated), overall, 69% of the 420 person-years lived were spent without treatment, and 72% without any HIV-related symptoms. Untreated children were without symptoms for 94% of these 5 y, whereas treated children spent nearly a third of their time with mild or moderately severe symptoms. CONCLUSIONS: Therapeutic management of paediatric HIV disease requires a balance between preventing disease progression and minimizing adherence problems and side effects. This is important, as most infected children are without symptoms most of the time. Recent European consensus guidelines for the treatment of infected children will facilitate management.

Adolescent↗
PubMed2003

Morbidity in children born to women infected with human immunodeficiency virus in South Africa: does mode of feeding matter?

AIM: To examine infant morbidity risks associated with refraining from breastfeeding where it is used in an attempt to prevent mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV). METHODS: The population consisted of infants born to HIV-infected women in South Africa who were participating in a vitamin A intervention trial to prevent MTCT of HIV. Women chose to breastfeed or formula feed their infants according to UNAIDS guidelines. Actual feeding practices and morbidity were recorded at clinic follow-up visits at I wk, 6 wk, 3 mo and every 3 mo thereafter until 15 mo of age or cessation of breastfeeding. The infant's HIV status was assessed according to a predetermined algorithm. RESULTS: HIV-infected infants who were never breastfed had a poorer outcome than those who were breastfed; 9 (60%) of those who were never breastfed had 3 or more morbidity episodes compared with 15 (32%) of breastfed children [odds ratio (OR) 4.05, 95% confidence interval (95% CI) 0.91-20.63, p = 0.05]. During the first 2 mo of life, never-breastfed infants (regardless of HIV status) were nearly twice as likely to have had an illness episode than breastfed infants (OR 1.91, 95% CI 1. 17-3.13, p = 0.006). CONCLUSION: The significant extra morbidity experienced in the first few months by all never-breastfed infants and at all times by HIV-infected infants who are not breastfed needs to be considered in all decisions by mothers, health workers and policy makers so as not to offset any gains achieved by decreasing HIV transmission through avoiding breastfeeding.

Adult↗
PubMed2001

Estimating the efficacy of interventions to prevent mother-to-child transmission of HIV in breast-feeding populations: development of a consensus methodology.

Postnatal transmission of HIV through breast milk complicates both the design of effective interventions to prevent mother-to-child transmission of HIV (PMTCT) and their evaluation. Estimated long-term efficacy in five African trials (four with peri-partum antiretrovirals and one with artificial feeding) varied from 25 to 50 per cent. This variation may be due, at least in part, to differences in analytical methodology. To facilitate direct comparison between trials, a methodological consensus approach to the analysis and presentation of the results of PMTCT trials was developed. The initial methodology used and results presented from African trials with available long-term efficacy data were reviewed during a workshop in Bordeaux, France, in September 2000. A consensus approach for evaluating efficacy applicable across PMTCT studies was developed. There are four typical situations defined by duration of follow-up (short versus long), and the available demographic (vital status) and biological data (single versus repeat HIV testing). Efficacy can be assessed from the risk of infection directly or from HIV-free survival by combining infection and death as a single endpoint. Studies should report results in a standardized format including infection, weaning, mortality and loss to follow-up. New statistical methods that account for the unknown date when a child would first test positive for HIV, for weaning as a competing risk for HIV infection, and for increased risk of death among HIV-infected children should be used in analysing data from PMTCT studies with repeat HIV testing. All estimates should be reported with confidence intervals. This standardized methodology that allows direct comparison between studies is now being applied to four randomized clinical trials.

Antiviral Agents↗
PubMed2001

Variation in breastmilk HIV-1 viral load in left and right breasts during the first 3 months of lactation.

The mechanism and risk factors associated with mother-to-child transmission of HIV-1 through breastfeeding remain unclear; breastmilk viral load may be an important determinant of transmission. Analysis of breastmilk cell-free viral load in samples taken from each breast at 1, 6 and 14 weeks postpartum showed that HIV-1 is shed intermittently and load may differ considerably between breasts of an individual woman at any given time. Breastmilk HIV-1 load was undetectable in approximately one-third of samples.

Breast↗
PubMed2001

Perinatal transmission of human immunodeficiency virus type 1 by pregnant women with RNA virus loads <1000 copies/ml.

In a collaboration of 7 European and United States prospective studies, 44 cases of vertical human immunodeficiency virus type 1 (HIV-1) transmission were identified among 1202 women with RNA virus loads <1000 copies/mL at delivery or at the measurement closest to delivery. For mothers receiving antiretroviral treatment during pregnancy or at the time of delivery (or both), there was a 1.0% transmission rate (8 of 834; 95% confidence interval [CI], 0.4%-1.9%), compared with 9.8% (36 of 368; 95% CI, 7.0%-13.4%) for untreated mothers (risk ratio, 0.10; 95% CI, 0.05-0.21). In multivariate analysis adjusting for study, transmission was lower with antiretroviral treatment (odds ratio [OR], 0.10; P<.001), cesarean section (OR, 0.30; P=.022), greater birth weight (P=.003), and higher CD4 cell count (P=.039). In 12 of 44 cases, multiple RNA measurements were obtained during pregnancy or at the time of delivery or within 4 months after giving birth; in 10 of the 12 cases, the geometric mean virus load was >500 copies/mL. Perinatal HIV-1 transmission occurs in only 1% of treated women with RNA virus loads <1000 copies/mL and may be almost eliminated with antiretroviral prophylaxis accompanied by suppression of maternal viremia.

Anti-HIV Agents↗
PubMed2001

Guidelines for the management of HIV infection in pregnant women and the prevention of mother-to-child transmission.

AIMS OF THE GUIDELINES: These guidelines, drawn up by a multidisciplinary group of clinicians and lay workers active in the management of pregnant women infected with HIV, aim to give up-to-date information on interventions to reduce the risk of mother to child transmission of the virus. The evidence on the use of interventions to prevent mother to child transmission of HIV has been graded according to the strength of the data as per the definitions of the US Agency for Health Care Policy and Research [1]. Weighted evidence on the use of combination antiretroviral therapy (ART) for the treatment of HIV infection per se is presented in the BHIVA guidelines for adults [2,3]. The highest level evidence (i.e. randomised controlled trials (RCTs) or large, well conducted meta-analyses) is only available for formula feeding, prelabour caesarean section and zidovudine monotherapy. The need to treat mothers for HIV infection has led to the widespread use of ART in pregnancy which in turn results in new questions such as how to deliver when the mother, on therapy, has no detectable plasma viraemia with the most sensitive assays. In addressing many common and/or difficult clinical scenarios in the absence of 'best evidence' the guidelines rely heavily on 'expert opinion'. Recommendations for management are given in the section on clinical scenarios, and summarized in Table 3. An expanded version of these guidelines with an appendix on safety and toxicity data is available on the BHIVA website http://www.bhiva.org. The authors are available to discuss individual cases.

Adult↗
PubMed2001

Fluctuations in symptoms in human immunodeficiency virus-infected children: the first 10 years of life.

OBJECTIVE: To describe patterns of clinical and immunologic progression in children who are vertically infected with the human immunodeficiency virus. METHODS: Children who were born to mothers who were infected with the human immunodeficiency virus in 11 European centers were enrolled at birth in a prospective study and followed according to a standard protocol. At each visit, a clinical and immunologic class was allocated according to guidelines of the Centers for Disease Control and Prevention (CDC). Progression to serious disease and death was assessed, allowing for available and actual antiretroviral therapy (ART). CDC class at each visit was assessed cross-sectionally. RESULTS: More than 15% of infected children will have progressed to category C or death by age 1 year and nearly 50% by 10 years. Just under 20% of children will have evidence of severe immunodeficiency by age 1 and 75% by 10 years. In general, immune status poorly reflected clinical condition. Children who were born after 1994, when the recommendation of earlier initiation of more active therapy was introduced, were significantly less likely to progress than those who were born when treatment was not widely available or was largely confined to zidovudine monotherapy. Estimated progression to CDC class C or death initially was faster in untreated than in treated children, but by 10 years estimated cumulative progression was similar in both groups. Treatment started before class C disease was associated with significantly slower progression. Cross-sectional analysis showed that children largely are symptom-free throughout their lives. After 4 years of age, fewer than 25% of infected children had symptoms at any one time, irrespective of ART received. CONCLUSION: Vertically infected children are without serious symptoms or signs for most of the time. The prognosis has improved with more widespread availability and use of combination ART. These findings have implications for health, education, and other support-service provision.

Age Distribution↗
PubMed2001

Prevention of mother-to-child transmission of HIV: challenges for the current decade.

In June 2001 the United Nations Special Assembly on HIV/AIDS set reduction targets of 20% and 50% for the numbers of children newly infected with HIV by 2005 and 2010 respectively. Are these targets achievable? Antiretroviral monotherapy during pregnancy, delivery, and the neonatal period can reduce the rate of mother-to-child transmission of HIV-1 by two-thirds in non-breastfeeding populations. Shorter and simpler regimens of monotherapy have been associated with a reduction of 50% in such transmission among non-breastfeeding populations and of up to 40% in breastfeeding populations. Delivery by elective caesarean section is associated with a halving of the risk of mother-to-child transmission. However, breastfeeding poses a substantial additional risk of acquisition of HIV, and if prolonged it more than doubles the overall rate of transmission. Rates below 2% are being reported from settings where combination therapy is applied during pregnancy and delivery, delivery is by elective caesarean section, and breastfeeding does not take place. In breastfeeding populations where elective caesarean delivery is not an option but peripartum antiretroviral therapy is used, rates at six weeks are about 10% but can be 25% or more after 18 months of breastfeeding. More widely applicable interventions are being developed, such as cleansing of the birth canal and antiretroviral therapy during the breastfeeding period.

Anti-HIV Agents↗
PubMed2000

Co-receptor usage of HIV-1 primary isolates, viral burden, and CCR5 genotype in mother-to-child HIV-1 transmission.

OBJECTIVE: To investigate the relationship between CC chemokine receptor 5 (CCR5) genotype, viral load and co-receptor usage of maternal HIV-1 isolates in perinatal HIV-1 transmission. PATIENTS AND METHODS: A total of 181 mothers and infants were studied at the time of delivery. Wild-type (wt) and delta32 CCR5 alleles were determined by means of polymerase chain reaction (PCR). The viral load in maternal plasma samples was determined by a quantitative reverse transcriptase-PCR assay; co-receptor usage of maternal isolates was determined by viral infection in cells stably expressing CCR5 or CXC chemokine receptor 4 (CXCR4) co-receptors. RESULTS: HIV-1 transmission rates in wt/wt and wt/delta32 mothers (14.7 versus 15.8%), and in wt/wt and wt/delta32 infants (14.6 versus 14.3%) were similar. Mothers transmitting infection to wt/delta32 infants had significantly higher HIV-1-RNA levels than those who transmitted infection to wt/wt infants (5.4 versus 4.1 log10 copies/ml, P = 0.03). In wt/wt children there was a positive relationship between transmission rate and maternal viral load over the entire range of HIV-1 values, whereas in wt/delta32 children transmission occurred only at viral loads greater than 4.0 log10 copies/ml. Logistic regression analysis confirmed that the relationship between viral load and transmission varied according to the child's CCR5 genotype (P = 0.035; adjusted for zidovudine prophylaxis and mode of delivery, P = 0.090). Moreover, the majority of wt/wt transmitting mothers had R5-type isolates, whereas none of the wt/delta32 mothers with an R5-type virus transmitted HIV-1 to their wt/delta32 infants. CONCLUSION: Taken together, these findings suggest that CCR5 delta32 heterozygosity exerts a protective effect against perinatal transmission in children exposed to a low maternal viral burden of an R5-type isolate.

Cetirizine↗
PubMed2000

Interventions to prevent vertical transmission of HIV-1: effect on viral detection rate in early infant samples.

OBJECTIVE: To determine whether mode of delivery or the use of maternal or neonatal antiretroviral prophylaxis influence the age when HIV-1 can first be detected in infected infants, particularly the probability of detection at birth. METHODS: In a collaboration between four multicentre studies, data on 422 HIV-1 infected infants who were assessed by HIV-1 DNA PCR or cell culture before 14 days of age were analysed. Weibull mixture models were used to estimate the cumulative proportion of infants with detectable levels of HIV-1 according to use of maternal/neonatal antiretroviral therapy (mainly zidovudine monotherapy) and mode of delivery. RESULTS: HIV-1 was detected in 162 infants (38%) when they were first tested, at a median age of 2 days. At birth, it was estimated that 36% [95% confidence interval (CI), 31-41%] of infants have levels of virus that can be detected by DNA PCR or cell culture. This percentage was not associated with either mode of delivery (35% for vaginal delivery versus 40% for cesarean section delivery; P = 0.4) or the use of maternal or neonatal antiretroviral prophylaxis. Among infants with undetectable levels of HIV-1 at birth, the median time to viral detectability was estimated to be 14.8 days (95% CI, 12.9-16.8 days). This time was increased by 15% (95% CI, -11 to 48%; P = 0.3) among infants who were exposed to antiretroviral therapy postnatally compared with infants who were not exposed. No effect was observed for mode of delivery. CONCLUSIONS: The outcome of an early virological test for HIV-1 is thought to be related directly to the timing of transmission and cesarean section delivery primarily reduces the risk of intrapartum transmission. The absence of an association between mode of delivery and viral detectability at birth was therefore unexpected. There was no evidence that foetal or neonatal exposure to prophylactic zidovudine delays substantially the diagnosis of infection, although this cannot be inferred for combination antiretroviral therapy.

Age Factors↗
PubMed2000

Preventing mother-to-child transmission of HIV-1 in Africa in the year 2000.

OBJECTIVES: Various approaches to preventing mother-to-child transmission (MTCT) of HIV have recently been, or are being, evaluated in developing countries, especially in Africa. New findings from these trials are now becoming available, the implications of which, for population-based intervention programmes, need urgent consideration. METHOD: A critical review of 18 randomized trials and other relevant studies from developing and industrialized countries. RESULTS: Most African results relate to trials of antiretroviral agents (ARV). They demonstrate efficacy in reducing transmission in the first 6 months of life with short regimens of zidovudine (ZDV), with or without lamivudine (3TC), and nevirapine (NVP) alone. Preliminary results suggest the long-term efficacy of zidovudine. Antiseptic and nutritional interventions have been shown to reduce maternal and infant mortality and morbidity but not MTCT of HIV. HIV confidential voluntary counselling and testing for pregnant women, a short regimen of peripartum ARV with alternatives to breastfeeding such as early weaning or breast milk substitutes from birth currently represent the best option to reduce MTCTof HIV in Africa. However, the prevention of postnatal transmission requires further research, particularly in view of the consequences of different feeding options and the possibility of post-perinatal exposure prophylaxis of newborns with ARV. Issues relating to the implementation of currently validated strategies are discussed.

Africa↗
PubMed2000

Subclinical mastitis as a risk factor for mother-infant HIV transmission.

Subclinical mastitis, as diagnosed by an elevated sodium/potassium ratio in milk accompanied by an increased milk concentration of the inflammatory cytokine, interleukin-8 (IL8), was found to be common among breast feeding women in Bangladesh and Tanzania. Subclinical mastitis results in leakage of plasma constituents into milk, active recruitment of leukocytes into milk, and possible infant gut damage from inflammatory cytokines. Therefore, we wished to investigate whether subclinical mastitis was related to known risk factors for postnatal mother-to-child HIV transmission, that is, high milk viral load or increased infant gut permeability. HIV-infected South African women were recruited at the antenatal clinic of McCord's Hospital, Durban. Risks and benefits of different feeding strategies were explained to them and, if they chose to breast feed, they were encouraged to do so exclusively. Women and infants returned to the clinic at 1, 6 and 14 weeks postpartum for an interview about infant health and current feeding pattern, a lactulose/mannitol test of infant gut permeability, and milk sample collection from each breast separately for analysis of Na/K ratio, IL8 concentration and viral load in the cell-free aqueous phase. Only preliminary cross-sectional analyses from an incomplete database are available at this point. Moderately (0.6-1.0) or greatly (>1.0) raised Na/K ratio was common and was often unilateral, although as a group right and left breasts did not differ. Considering both breasts together, normal, moderately raised or greatly raised Na/K was found, respectively, in 51%, 28%, 21% of milk samples at 1 week (n=190); 69%, 20%, 11% at 6 weeks (n=167); and 72%, 16%, 12% at 14 weeks (n=122). IL8 concentration significantly correlated with both Na/K and viral load at all times. Na/K correlated with viral load at 1 and 14, but not 6 weeks. At 1 and 14 weeks, geometric mean viral loads in samples with Na/K > 1.0 were approximately 4 times those in samples with Na/K < 0.6. At 1 week but not later times, exclusive breast feeding was associated with lower milk viral load than was mixed feeding. Gut permeability was unrelated to milk Na/K ratio or IL8 concentration and was not significantly increased by inclusion of other foods than breast milk in the infant's diet. The results suggest that subclinical mastitis among HIV-infected women may increase the risk of vertical transmission through breast feeding by increasing milk viral load. The importance of various causes of subclinical mastitis, which likely differ at 1 week from at later times and may include local infection or sterile inflammation, systemic infection, micronutrient deficiencies, or poor lactation practices, needs to be further clarified so that appropriate interventions can be implemented.

Africa South of the Sahara↗
PubMed2000

Variable use of therapeutic interventions for children with human immunodeficiency virus type 1 infection in Europe.

UNLABELLED: Although a range of antiretroviral drugs are available for use in children, the appropriate paediatric regimen remains unclear. In a survey to investigate policies and practices relating to the therapeutic management of children infected by the human immunodeficiency virus (HIV), a postal questionnaire was sent to a named paediatrician in 70 major HIV centres in 13 European countries in early 1998. A total of 64 paediatricians (91%) responded. Pneumocystis carinii pneumonia prophylaxis was found to be routine in all centres, although considerable variation existed regarding the time of starting and stopping therapy. Prophylaxis for fungal infections and recurrent bacterial infections was common, with cytomegalovirus prophylaxis being less frequent. Although most centres (89%) used all five currently available nucleoside analogues (ziduvodine, lamivudine, stavudine, didanosine, zalcitabine), there was considerable variability regarding the availability of protease inhibitors. Most respondents delayed initiation of antiretroviral therapy until evidence of disease progression was apparent. The initial prescription of 38% of clinicians was triple therapy and that of 57% prescribed double therapy. Policies varied regarding the modification to regimens in response to disease progression and emergence of side effects and drug resistance. Clinical practice was informed by a number of sources, including centre-specific and national guidelines. Most respondents affirmed the need for European guidelines. CONCLUSION: Approaches to the therapeutic management of paediatric human immunodeficiency virus infection differ across Europe.

Antiviral Agents↗