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Biomedical subjects

R J Simonds

Publications and source records attributed to R J Simonds.

At least 37 records · Page 2Linked to original sources
PubMed1999

Short-course zidovudine for perinatal HIV-1 transmission in Bangkok, Thailand: a randomised controlled trial. Bangkok Collaborative Perinatal HIV Transmission Study Group.

BACKGROUND: Many developing countries have not implemented the AIDS Clinical Trials Group 076 zidovudine regimen for prevention of perinatal HIV-1 transmission because of its complexity and cost. We investigated the safety and efficacy of short-course oral zidovudine administered during late pregnancy and labour. METHODS: In a randomised, double-blind, placebo-controlled trial, HIV-1-infected pregnant women at two Bangkok hospitals were randomly assigned placebo or one zidovudine 300 mg tablet twice daily from 36 weeks' gestation and every 3 h from onset of labour until delivery. Mothers were given infant formula and asked not to breastfeed. The main endpoint was babies' HIV-1-infection status, tested with HIV-1-DNA PCR at birth, 2 months, and 6 months. We measured maternal plasma viral concentrations by RNA PCR. FINDINGS: Between May, 1996, and December, 1997, 397 women were randomised; 393 gave birth to 395 live-born babies. Median duration of antenatal treatment was 25 days, and median number of doses during labour was three. 99% of women took at least 90% of scheduled antenatal doses. Adverse events were similar in the study groups. Of 392 babies with at least one PCR test, 55 tested positive: 18 in the zidovudine group and 37 in the placebo group. The estimated transmission risks were 9.4% (95% CI 5.2-13.5) on zidovudine and 18.9% (13.2-24.2) on placebo (p=0.006; efficacy 50.1% [15.4-70.6]). Between enrolment and delivery, women in the zidovudine group had a mean decrease in viral load of 0.56 log. About 80% of the treatment effect was explained by lowered maternal viral concentrations at delivery. INTERPRETATION: A short course of twice-daily oral zidovudine was safe and well tolerated and, in the absence of breastfeeding, can lessen the risk for mother-to-child HIV-1 transmission by half. This regimen could prevent many HIV-1 infections during late pregnancy and labour in less-developed countries unable to implement the full 076 regimen.

Administration, Oral↗
PubMed1999

Distinct risk factors for intrauterine and intrapartum human immunodeficiency virus transmission and consequences for disease progression in infected children. Perinatal AIDS Collaborative Transmission Study.

Predictors and prognosis of intrauterine and intrapartum human immunodeficiency virus (HIV) transmission were investigated among 432 children of HIV-infected women in the Perinatal AIDS Collaborative Transmission Study. Timing of transmission was inferred from polymerase chain reaction or viral culture within 2 days of birth. Proportions of infections due to intrauterine transmission were similar among women using (29%) or not using zidovudine (30%). Preterm delivery was strongly associated with intrapartum transmission (relative risk, 3.7; 95% confidence interval [CI], 2.2-6.1), particularly among infants delivered longer after membrane rupture, but was not associated with intrauterine transmission. Progression to AIDS or death increased 2.5-fold (95% CI, 1.1-5.8) among intrauterine infected children, adjusting for preterm delivery, and maternal CD4 cell count. Early transmission appears unlikely to explain instances of zidovudine failure. Preterm infants may be more vulnerable to HIV acquisition at delivery, especially if membrane rupture is prolonged. Intrauterine infection does not appear to increase risk of preterm delivery.

Anti-HIV Agents↗
PubMed1998

International multicentre pooled analysis of late postnatal mother-to-child transmission of HIV-1 infection. Ghent International Working Group on Mother-to-Child Transmission of HIV.

BACKGROUND: An understanding of the risk and timing of mother-to-child transmission of HIV-1 in the postnatal period is important for the development of public-health strategies. We aimed to estimate the rate and timing of late postnatal transmission of HIV-1. METHODS: We did an international multicentre pooled analysis of individual data from prospective cohort studies of children followed-up from birth born to HIV-1-infected mothers. We enrolled all uninfected children confirmed by HIV-1-DNA PCR, HIV-1 serology, or both. Late postnatal transmission was taken to have occurred if a child later became infected. We calculated duration of follow-up for non-infected children from the time of negative diagnosis to the date of the last laboratory follow-up, or for infected children to the mid-point between the date of last negative and first positive results. We stratified the analysis for breastfeeding. FINDINGS: Less than 5% of the 2807 children in four studies from industrialised countries (USA, Switzerland, France, and Europe) were breastfed and no HIV-1 infection was diagnosed. By contrast, late postnatal transmission occurred in 49 (5%) of 902 children in four cohorts from developing countries, in which breastfeeding was the norm (Rwanda [Butare and Kigali], Ivory Coast, Kenya), with an overall estimated risk of 3.2 per 100 child-years of breastfeeding follow-up (95% CI 3.1-3.8), with similar estimates in individual studies (p=0.10). Exact information on timing of infection and duration of breastfeeding was available for 20 of the 49 children with late postnatal transmission. We took transmission to have occurred midway between last negative and first positive HIV-1 tests. If breastfeeding had stopped at age 4 months transmission would have occurred in no infants, and in three if it had stopped at 6 months. INTERPRETATION: Risk of late postnatal transmission is consistently shown to be substantial for breastfed children born to HIV-1-positive mothers. This risk should be balanced against the effect of early weaning on infant mortality and morbidity and maternal fertility.

Blotting, Western↗
PubMed1998

Sensitivity and specificity of a qualitative RNA detection assay to diagnose HIV infection in young infants. Perinatal AIDS Collaborative Transmission Study.

OBJECTIVE: To evaluate the sensitivity and specificity of an RNA detection assay for diagnosing perinatal HIV infection. METHODS: Plasma and serum specimens taken during the first 3 months of life from HIV-infected and uninfected children enrolled in a cohort study were assayed for HIV RNA using the qualitative nucleic acid sequence-based amplification (NASBA) kit. Sensitivity, specificity, and predictive values were calculated. NASBA results from infected children were compared with DNA PCR results from the same blood samples. Autoantibody patterns of suspected false-positive specimens were compared with those of subsequent specimens from the same child to exclude specimen labelling errors. RESULTS: Amongst 131 specimens from 105 HIV-infected children, the sensitivity of the qualitative NASBA assay was 13 out of 34 [38%; 95% confidence interval (CI), 22-56] at < 7 days, 56 out of 58 (97%; 95% CI, 88-100) at 7-41 days, and 37 out of 39 (95%; 95% CI, 83-99) at 42-93 days of life. Of 252 specimens from 206 uninfected children, six tested positive and one tested indeterminate by NASBA. Four of these positive specimens had discordant autoantibody patterns suggesting mislabelling; excluding these, the test specificity was 245 out of 248 (99%; 95% CI, 97-100). Amongst 128 paired specimens from infected children, NASBA results were more often positive than those from DNA PCR (103 versus 92; P=0.01). Amongst infants with specimens drawn in the first week of life, the proportion born after > 4 h of membrane rupture was greater amongst those testing negative (81%) than those testing positive (46%; P=0.05). CONCLUSIONS: The qualitative NASBA RNA assay is highly specific and more sensitive than DNA PCR. Qualitative RNA assays may be useful for diagnosing and excluding perinatal HIV infection in children after the first week of life for such purposes as initiating antiretroviral therapy and other treatment, resolving parental uncertainty, determining timing of transmission, and providing endpoints for intervention trials.

Cohort Studies↗
PubMed1998

Impact of zidovudine use on risk and risk factors for perinatal transmission of HIV. Perinatal AIDS Collaborative Transmission Studies.

OBJECTIVES: To evaluate the impact of perinatal zidovudine use on the risk of perinatal transmission of HIV and to determine risk factors for transmission among women using perinatal zidovudine. DESIGN: Prospective cohort study of 1533 children born to HIV-infected women between 1985 and 1995 in four US cities. METHODS: The association of potential risk factors with perinatal HIV transmission was assessed with univariate and multivariate statistics. RESULTS: The overall transmission risk was 18% [95% confidence interval (CI), 16-21]. Factors associated with transmission included membrane rupture > 4 h before delivery [relative risk (RR), 2.1; 95% CI, 1.6-2.7], gestational age < 37 weeks (RR, 1.8; 95% CI, 1.4-2.2), maternal CD4+ lymphocyte count < 500 x 10(6) cells/l (RR, 1.7; 95% CI, 1.3-2.2), birthweight < 2500 g (RR, 1.7; 95% CI, 1.3-2.1), and antenatal and neonatal zidovudine use (RR, 0.6; 95% CI, 0.4-0.9). For infants exposed to zidovudine antenatally and neonatally, the transmission risk was 13% overall but was significantly lower following shorter duration of membrane rupture (7%) and term delivery (9%). The transmission risk declined from 22% before 1992 to 11% in 1995 (P < 0.001) in association with increasing zidovudine use and changes in other risk factors. CONCLUSIONS: Perinatal HIV transmission risk has declined with increasing perinatal zidovudine use and changes in other factors. Further reduction in transmission for women taking zidovudine may be possible by reducing the incidence of other potentially modifiable risk factors, such as long duration of membrane rupture and prematurity.

Adult↗
PubMed1998

Thymic dysfunction and time of infection predict mortality in human immunodeficiency virus-infected infants. CDC Perinatal AIDS Collaborative Transmission Study Group.

The effect of human immunodeficiency virus (HIV)-induced thymic dysfunction (TD) on mortality was studied in 265 infected infants in the CDC Perinatal AIDS Collaborative Transmission Study. TD was defined as both CD4 and CD8 T cell counts below the 5th percentile of joint distribution for uninfected infants within 6 months of life. The 40 HIV-infected infants with TD (15%) had a significantly greater mortality than did the 225 children without TD (44% vs. 9% within 2 years). Infants with TD infected in utero had higher mortality than did those infected intrapartum (70% vs. 37% within 2 years), while no significant difference was noted between infants without TD with either mode of transmission. The TD profile was independent of plasma virus load. Virus-induced TD by particular HIV strains and the time of transmission are likely to explain the variation in pathogenesis and patterns of disease progression and suggest the need for early aggressive therapies for HIV-infected infants with TD.

CD4 Lymphocyte Count↗
PubMed1997

Ethics of HIV trials.

Explore the source record for details and available documents.

Controlled Clinical Trials as Topic↗
PubMed1997

Diagnosis of perinatal human immunodeficiency virus infection by polymerase chain reaction and p24 antigen detection after immune complex dissociation in an urban community hospital.

Results of polymerase chain reaction (PCR) and p24 antigen detection after immune complex dissociation (p24-ICD) were compared with antibody results after 18 months of age for human immunodeficiency virus (HIV) diagnosis in 345 prospectively followed, perinatally exposed infants. Of 59 infected and 286 uninfected infants tested at 1-6 months of age, sensitivity and specificity were, respectively, 100% and > 97% for PCR and 90% and > 97% for p24-ICD. Testing was done on > or = 2 occasions in the first 6 months of life in 43 infected infants; 77% had > or = 2 positive results with the same test. Of these infants, 68% had 2 positive p24-ICD tests. In uninfected infants, 96% had only negative tests; none had > 1 positive. By 6 months, all uninfected infants with > or = 2 PCR results could have been diagnosed. HIV status can be determined by PCR by age 6 months in most HIV-exposed infants. p24-ICD should not be used alone, because of its lower sensitivity, but may be useful in areas without advanced laboratory support.

Antigen-Antibody Complex↗
PubMed1996

Cost-effectiveness of short-course zidovudine to prevent perinatal HIV type 1 infection in a sub-Saharan African Developing country setting.

OBJECTIVE: To evaluate the cost-effectiveness of a short-course zidovudine program to prevent perinatal transmission of human immunodeficiency virus (HIV) type 1 in sub-Saharan African country settings. DESIGN AND SETTING: Several clinical trials of short-course zidovudine during pregnancy for prevention of perinatal transmission of HIV are under way in developing countries in sub-Saharan Africa. A decision model was used to examine the cost-effectiveness of zidovudine programs in a hypothetical 1-year birth cohort in a sub-Saharan African setting from the perspective of the health care system and of society. A completed short course of zidovudine was assumed to reduce perinatal HIV transmission from 25% to 16.5%, approximately one half of the effect of the longer-course zidovudine. Estimates of program costs, lifetime HIV-related health care costs, and lost productivity costs were derived from the published literature and from preliminary data available from sites of planned clinical trials. Sensitivity analyses were conducted on all relevant parameters. MAIN OUTCOME MEASURES: Medical costs, lost productivity costs, program costs, cost savings, and incremental cost-effectiveness, expressed as cost per infant HIV infection prevented. RESULTS: The model estimated that a national zidovudine program in a setting with 12.5% HIV seroprevalence would reduce perinatal HIV incidence by 12% (4.9 infections per 1000 births). The costs to the health care system would be $3748 per infant HIV infection prevented. When productivity losses were included in the model, the cost decreases to $1115 per infant HIV infection prevented. The cost to implement a national zidovudine program including the cost of counseling, testing, and drugs, would be $2 million per 100,000 births or $20 per pregnant woman. In the base case, decreases in the cost of counseling and testing and increases in maternal HIV prevalence, zidovudine efficacy, and medical and lost productivity costs improved cost-effectiveness of the zidovudine program. CONCLUSIONS: Assuming demonstrable efficacy of short-course zidovudine prevention of perinatal HIV, a national perinatal HIV prevention program with zidovudine in most sub-Saharan African country settings would reduce the incidence of infant HIV infection and, in some settings, provide societal savings; however, substantial initial investment in such programs will be required. Where health care resources are limited, as in these regions, allocation of resources to a perinatal zidovudine program will need to be considered in the context of resources required for other pressing medical care needs.

Africa South of the Sahara↗
PubMed1996

Infection control practices in the home: a survey of households of HIV-infected persons with hemophilia.

OBJECTIVE: To assess infection control practices and risk for human immunodeficiency virus (HIV) transmission in households where home infusion for hemophilia is used. DESIGN: Cross-sectional prospective survey from 1992 through 1994. SETTING: Hemophilia treatment centers. PARTICIPANTS: Human immunodeficiency virus (HIV)-infected persons with hemophilia who receive home infusions of clotting factor concentrate and their household members. MAIN OUTCOME MEASURES: Frequency of specific infection control practices in the home and the risk of HIV transmission to household members. RESULTS: We surveyed 235 persons from 75 families (79 HIV-infected persons with hemophilia and 156 household members) about infection control practices in the home. Forty-eight percent of household members surveyed helped with the infusion process. Of 74 members who assisted with infusion, 13 (18%) had sustained a needlestick injury, 11 of whom were injured during the past year. One hundred fifty household members tested for antibody to HIV were antibody negative. These household members had a total of 903 person-years of contact after HIV was diagnosed in the index case. Household members' adherence to recommended infection control measures was highest for washing hands after cleaning up infusion equipment and waste, and for using sharps disposal containers. Adherence was lowest for wearing gloves when helping with infusions and proper disposal of bloody waste from the infusion. CONCLUSIONS: No HIV transmission was found among persons living with HIV-infected persons with hemophilia, although there was a high rate of needlestick injuries during home infusion. Because persons who assisted with infusions often did not wear gloves and many households did not dispose of bloody waste properly, hemophilia treatment center personnel should emphasize these areas when training for home infusion. Adherence to appropriate infection control practices should help to keep the risk of HIV transmission in households extremely low.

Adolescent↗
PubMed1996

Attitudes, practices, and infection risks of hemophilia treatment center nurses who teach infection control for the home.

OBJECTIVE: To examine the practices toward infection control training and to assess the attitudes about, and risks for, exposures to blood among hemophilia treatment center (HTC) nurses who teach home infusion therapy (HIT). DESIGN AND POPULATION: Written and telephone interview surveys of the 153 nurses who teach HIT at federally funded HTCs. MAIN OUTCOME MEASURES: Hemophilia treatment center nurses' teaching practices and infection control messages taught, and frequency of exposures to blood. RESULTS: The response rate to the written nurses' survey was 60% and to the telephone interview 88%. Nurses taught patients a median of three HIT sessions totaling 4 hours of instruction. Reevaluation of patients' HIT practices took place every 6 months by 22% and every 12 months by 59% of nurses. Nurses frequently reported teaching proper use of a sharps disposal container (99%) and gloves (93%), but less often reported teaching patients to wash hands after infusions (26%) and to report needlestick injuries to HTCs (11%). The respondents identified several barriers to effective infection control as it is practiced in the home by patients. Although at least 30% of HTC nurses recalled having had percutaneous exposure to blood, they considered their risk for hepatitis B infection low but greater than for infection with the human immunodeficiency virus (HIV). CONCLUSIONS: While some important infection control messages are stressed during HIT teaching, others may be underemphasized. Failure to instruct patients about all infection control precautions may be related to nurse educators' perception of low to moderate personal risk for hepatitis B and HIV infection. Patients receiving HIT, and those who assist them, need to be fully aware of, and to have reinforced periodically, universal infection control strategies in the home.

Health Knowledge, Attitudes, Practice↗