Biomedical subjects

N L Young

Publications and source records attributed to N L Young.

At least 19 recordsLinked to original sources

PubMed2006

Comparing two measures of quality of life for children with haemophilia: the CHO-KLAT and the Haemo-QoL.

Disease-specific measures of quality of life (QoL) for children with haemophilia are now available for use in clinical studies [Haemophilia, 10, 2004, 9-16]. One of these measures, the Canadian Haemophilia Outcomes - Kids' Life Assessment Tool (CHO-KLAT), was developed in Canada with emphasis on the perspectives of children [Pediatr Blood Cancer, 47, 2006, 305-11; Haemophilia, 10, 2004, 34-43]. Another, the Haemo-QoL, was developed in Europe, with emphasis on the perspectives of clinicians [Haemophilia, 8, 2002, 47-54; Haemophilia, 10, 2004, 17-25]. While these two measures are unique and independent, researchers from both studies were collaboratively linked throughout development and testing. This study presents the results of a joint assessment of the two measures with respect to their strengths, limitations and unique contributions. The primary questions addressed were: 1 What is the relationship between the CHO-KLAT and the Haemo-QoL in terms of summary scores and item content? 2 What are the methodological strengths, limitations and unique contributions of each measure? We conducted a retrospective analysis of data from field testing of both measures. The analysis included a comparative assessment of the basic validity, reliability and items used in each measure. Overall, the CHO-KLAT and the Haemo-QoL are promising and valuable measures of QoL for children with haemophilia. Our analyses confirmed the basic psychometric properties of both tools, but identified some discrepancies between them. Additional data will allow for greater understanding of these discrepancies and lend clarity to how the tools should be used in clinical studies (separately or merged). The present recommendation is that the measures be run independently, but preferably concurrently in studies of children with haemophilia.

Adolescent↗

PubMed2005

Developing a disease activity tool for systemic-onset juvenile idiopathic arthritis by international consensus using the Delphi approach.

OBJECTIVES: The systemic form of juvenile idiopathic arthritis may present with many diverse symptoms, signs and laboratory abnormalities. Our aim was to elicit and pool items useful for developing a consensus disease activity measure for systemic arthritis in children, using an international pool of respondents. METHODS: We used a Delphi survey process in two steps. First we surveyed 187 paediatric rheumatologists and allied health professionals. We elicited 2607 items that, when combined with previously elicited items from parents/patients, could be pooled into 107 independent items. We then surveyed the paediatric rheumatologists to determine the frequency and importance of the 107 items. RESULTS: Our response rate was 83% to both surveys. We identified 29 items as being the most important and most frequently seen indicators of active disease. The most highly rated of these items were: presence of fever, presence of rash, elevated ESR, elevated CRP, requirement for increasing medications, abnormal physician global evaluation and presence of joints with active arthritis. CONCLUSIONS: Twenty-nine items are thought by medical practitioners to be most relevant in determining disease activity in systemic arthritis. As a next step, the measurement properties of these items will be tested to help develop a disease activity tool.

Algorithms↗

PubMed2005

What does "active disease" mean? patient and parent perceptions of disease activity in the systemic arthritis form of juvenile idiopathic arthritis (SO-JIA).

OBJECTIVE: The systemic onset form of juvenile idiopathic arthritis (SO-JIA) is a very serious chronic illness of childhood. At present, there is no specific tool to measure disease activity for SO-JIA. Our long-term goal is to develop a disease activity measure for SO-JIA using a consensus (Delphi) approach. In preparation for the development of this measure, we interviewed both patients and their parents. We sought to elicit specific items reflecting their perceptions of active disease that may be considered for inclusion in a disease activity measure for SO-JIA. METHODS: SO-JIA patients followed at The Hospital for Sick Children and their parents were chosen by purposive sampling. A trained research coordinator interviewed all participants using open-ended questions to elicit aspects of disease activity (defined as reversible manifestations of disease) of relevance to families. A list of these aspects was then generated and organized by categories to allow item reduction. RESULTS: Fourteen patients (eight females) with a mean age of 11.8 yr (mean disease duration 5.2 yr) and their parents were interviewed. A total of 292 items were generated, with an average of 11 items generated per interview. Arthralgia, ambulation difficulties, rash, decreased energy level and fever were the most common items mentioned by patients and their parents. Mood disturbances, decreased activity levels, arthritis severity and decreased school attendance were also common items identified as relevant aspects of disease activity. CONCLUSION: This study has allowed us to include patient and parent perspectives in preparation for developing a disease activity measure for SO-JIA. The resulting items will be added to future physician surveys in the further development and validation of a disease activity measure for SO-JIA.

Adolescent↗

PubMed2004

Health-related quality of life (HRQL) scores reported from parents and their children with chronic illness differed depending on utility elicitation method.

OBJECTIVE: To describe the relationship between health-related quality of life (HRQL) as measured by utility when elicited from parents and their children with chronic illness. STUDY DESIGN AND SETTING: We enrolled families of children admitted for cancer chemotherapy and those attending outpatient rheumatology, hemophilia and bone marrow transplantation clinics. Children in grade 6 or higher were included. The child's HRQL was rated by parent and child using the Standard Gamble (SG), Visual Analogue Scale (VAS), Time Trade-Off (TTO), and Health Utilities Index Mark 2/3 (HUI2 and HUI3). RESULTS: 22 families were included. The mean parent SG was 0.92 +/- 0.09, which was similar to the mean SG elicited from their children of 0.92 +/- 0.10. The parent and child SG were moderately concordant (ICC=0.64, 95% CI=0.30, 0.83; P=.0005). In contrast, TTO scores were not concordant (ICC=0.14, 95% CI=-0.29, 0.53; P=.3), with parents (mean TTO=0.77 +/- 0.31) rating HRQL worse than children (mean TTO=0.92 +/- 0.11; P=.04). Similarly, the mean parent HUI2 of 0.82 +/- 0.22 was lower than the child HUI2 of 0.95 +/- 0.07; P=.02 and HUI2 were not concordant (ICC=0.11, 95% CI=-0.35, 0.53; P=.3) between parents and children. CONCLUSION: Parents and children rate HRQL similarly according to SG, but parents rate HRQL significantly worse using TTO and HUI2.

Adolescent↗

PubMed2004

Development of a health-related quality of life measure for boys with haemophilia: the Canadian Haemophilia Outcomes--Kids Life Assessment Tool (CHO-KLAT).

Several measures of quality of life (QoL) are available for children with haemophilia. However, most are not disease-specific and few focus on children's perspectives. The purpose of this study was to develop a psychometrically sound measure of QoL that included the perspectives of boys with haemophilia. A list of potential items was developed from the literature, other measures, and input from five discussion sessions with adults with haemophilia, children with haemophilia and their parents and haemophilia nurses. The list was augmented with items generated by three focus groups with children and three focus groups with parents. These groups also prioritized items and recommended a domain structure. Supplemental information was gathered by surveying haematologists. Data from all sources were analysed to reduce the number of items using a two-step approach, based on rules that weighted the children's priorities most heavily. The remaining items were compiled into a questionnaire that was pilot tested with 10 children and their parents. The total item pool contained 228 potential items. Of these, 33 were removed based on three focus groups and survey responses, 72 were removed after the completion of all focus groups and 46 were removed due to redundancy. This resulted in a 77-item version of the CHO-KLAT. Pilot testing identified the need to subdivide two items, resulting in a 79-item CHO-KLAT. The CHO-KLAT is a promising disease-specific measure of QoL that reflects children's unique perspectives. This child-centric focus distinguishes the CHO-KLAT from alternative measures of QoL. Further research will assess the measurement properties of the CHO-KLAT.

Adolescent↗

PubMed2004

Disease-specific quality-of-life measurement tools for haemophilia patients.

The purpose of this paper is to summarize the state of the art in measuring quality of life in haemophila populations. The paper reviews the measures recently included in haemophila trials in the published literature. It also summarizes the development of four new disease-specific measures of health-related quality of life. Two of these were developed for children (the Haemo-QoL and the CHO-KLAT), and two for adults (the Hemofilia-QoL and the Hemolatin-QoL). These new measures show promise for use in clinical trials. Further research is in progress to complete the psychometric testing and cross-cultural validation.

Adolescent↗

PubMed2003

Construct validation of the Health Utilities Index and the Child Health Questionnaire in children undergoing cancer chemotherapy.

The objective of this study was to evaluate the construct validity of two questionnaire-based measures of health-related quality of life (HRQL) in children undergoing cancer chemotherapy: the Health Utilities Index (HUI) and the Child Health Questionnaire (CHQ). Subjects were children hospitalised for chemotherapy. To examine construct validity: (1). a priori expected relations between CHQ concepts and HUI attributes were examined; (2). HUI and CHQ summary scores were compared to visual analogue scale (VAS) scores. Ease of completion was rated using a 5-point categorical scale and completion time was recorded. A total of 36 subjects were included. The maximum score was seen in 15 (47%) of HUI3 assessments. As predicted, CHQ body pain was moderately correlated with HUI3 pain (r=0.51), CHQ physical functioning was moderately correlated with HUI2 mobility (r=0.58) and CHQ mental health was moderately correlated with HUI2 emotion (r=0.53). Only the CHQ psychosocial subscale (and not HUI) was correlated with VAS (r=0.44). The CHQ and the HUI were both easy to use. The HUI questionnaires required less time to complete (mean=3.1, s.d.=1 min) compared with CHQ (mean=13.1, s.d.=3.4 min, P<0.0001). In conclusion, HUI and CHQ demonstrated construct validity in children undergoing cancer chemotherapy. The Health Utilities Index is subject to a ceiling effect whereas CHQ requires more time to complete.

Adolescent↗

PubMed2003

Validity of a modified standard gamble elicited from parents of a hospital-based cohort of children.

OBJECTIVES: To examine the validity of a modified standard gamble (Mod SG) (nondeath baseline) by comparing these scores to SG (death baseline), time trade off (TTO), visual analog scale (VAS), Health Utilities Index (HUI), and Child Health Questionnaire (CHQ). METHODS: Respondents were parents of in-patients with cancer receiving chemotherapy and parents of children without cancer attending outpatient clinics. Construct validity was determined by comparing a priori hypotheses to actual correlations between measures. Discriminant validity was examined by anticipating that in-patients with cancer would have lower HRQL than outpatients. RESULTS: 85 families were included. Both Mod SG and SG were moderately correlated with TTO (r=0.50 and r=0.49; P<.01 for both). Both Mod SG and SG were moderately correlated with TTO (r=0.47 and r=0.05, P<0.002 for both). CONCLUSION: The Mod SG did not perform better than SG. Two nonoverlapping groups of HRQL measures were demonstrated.

Adolescent↗

PubMed2003

Rasch analysis of the Western Ontario McMaster (WOMAC) Osteoarthritis Index: results from community and arthroplasty samples.

BACKGROUND AND OBJECTIVE: This study is based on secondary analysis of Western Ontario McMaster Osteoarthritis Index (WOMAC) data from a community sample over 55 years and total hip or knee arthroplasty samples presurgery and 1-year postoperative. METHODS: The WOMAC data were evaluated by Rasch analysis. Data were considered to fit the Rasch mathematical model for the pain and physical dimensions of the WOMAC if unidimensionality was confirmed by principle component analysis of the subscale and the residuals from the Rasch analysis, infit and outfit statistics were in the range of 0.80 to 1.20; if there was no differential item functioning based on gender or hip vs. knee subjects; and, if there was stability of the item logits across the three data samples. RESULTS: A three-item pain dimension (excluding night pain and pain on standing) and a 14-item physical dimension (excluding heavy domestic duties, getting in and out of the bath and getting on and off the toilet) fit the Rasch model based on these criteria. CONCLUSION: In evaluating existing health status questionnaires using Rasch methodology, it is important to evaluate relevant patient samples and longitudinal data when the measure is intended to evaluate change in status. By these criteria, a modified WOMAC questionnaire fits the Rasch model and has interval-level scaling properties.

Aged↗

PubMed2001

An HLA-directed molecular and bioinformatics approach identifies new HLA-A11 HIV-1 subtype E cytotoxic T lymphocyte epitopes in HIV-1-infected Thais.

Only limited cytotoxic T lymphocyte (CTL) epitope mapping has been done in nonsubtype B HIV-infected persons. We used molecular immunogenetic tools to determine HIV-specific CTL responses in HIV-1 Env subtype E-infected female sex workers (FSWs) from northern Thailand, where more than 50% of the population is HLA-A11 positive. EpiMatrix, a computer-based T cell epitope prediction algorithm, and a manual editing approach were used to predict 77 possible HLA-A11 CTL epitopes in HIV-1, some of which were conserved between subtypes B and E. MHC binding of these peptides was determined in an HLA-A11 stabilization assay, and binding peptides were tested for CTL recognition in eight HLA-A11-positive FSWs. Subtype E versions of known HLA-A2 subtype B HIV epitopes were also tested in four HLA-A2 positive FSWs. CTL responses were detected in all HLA-A11-positive and in three of four HLA-A2-positive persons. Among the 12 FSWs responses to peptides were found to Pol in 9 (75%), Env in 7 (58%), Nef in 5 (42%), and Gag in 5 (42%), and to conserved epitopes in 8 (67%). To identify HLA-A11 CTL epitopes in the absence of prediction tools, it would have been necessary to test almost 3000 10-mer peptides. EpiMatrix and manual predictions reduced this number to 77, of which 26 were MHC binding and 12 were CTL epitopes. Six of these HLA-A11 CTL epitopes have not been previously reported and are located in RT, gp120, and gp41. This report of CTL responses in subtype E-infected individuals defines epitopes that may be useful in HIV pathogenesis or vaccine studies.

Algorithms↗

PubMed2001

HIV-specific cytotoxic T lymphocytes, HLA-A11, and chemokine-related factors may act synergistically to determine HIV resistance in CCR5 delta32-negative female sex workers in Chiang Rai, northern Thailand.

Understanding how highly HIV-exposed individuals remain HIV uninfected may be useful for HIV vaccine design and development of new HIV prevention strategies. To elucidate mechanisms associated with resistance to HIV infection, immunologic and genetic factors were examined in 14 HIV-exposed but persistently seronegative (HEPS) female sex workers from Chiang Rai, northern Thailand and in ethnically matched, HIV-positive (n = 9) and HIV-negative women (n = 9). The HEPS women were identified in a study of commercial sex workers who had an HIV-1 incidence of 20.3 per 100 person-years. A high frequency of HLA-A11 was observed in HEPS women (86%) compared with northern Thai controls (56%). HIV-specific cytotoxic T lymphocyte (CTL) lytic responses were detected in cryopreserved peripheral blood mononuclear cells (PBMCs), using HLA-A-matched subtype E HIV-1 peptides in four of seven (57%) HEPS women, eight of eight HIV-positive women, and zero of nine HIV-negative unexposed controls (p = 0.019 HEPS women vs. HIV-negative controls). CTL lysis levels were low, but responses were detected to peptides from Nef, Pol, Gag, and Env. Nef responses predominated in HEPS women. Compared with controls, HEPS women tended to have higher frequencies of CCR5 promotor 59402GG and SDF-1 3'UTR 801A genotypes known to influence HIV transmission or course of disease. HEPS women also had higher levels of spontaneous RANTES production by PBMCs than other groups. Each of these factors could potentially contribute to HIV resistance. As most HEPS women had one or more of these factors, they may prevent HIV infection synergistically by blocking HIV cell entry, delaying its dissemination, or killing HIV-infected cells.

Adult↗

PubMed2001

Production of a novel viral suppressive activity associated with resistance to infection among female sex workers exposed to HIV type 1.

To investigate mechanisms of natural resistance to human immunodeficiency virus type 1 (HIV-1), we obtained blood samples from eight women who remained HIV-1 negative after > 3 years of high-risk sex work in Chiang Rai, Thailand. CD4+ T lymphocytes from these highly exposed, persistently seronegative (HEPS) women were readily infectable in vitro with HIV-1 subtypes B and E. Autologous CD8+ cell suppression of both HIV-1 subtypes was evident in HEPS infection cultures, but to an extent also observed in cultures from non-HIV-exposed individuals. Furthermore, production of beta-chemokines was not enhanced in HEPS cultures. However, HEPS cultures displayed significantly enhanced production of a soluble activity that suppressed postintegrated HIV-1 replication. This activity was the unique product of CD4+ T cell and monocyte cocultures. Therefore, although HEPS individuals are apparently susceptible to infection, the production of a postintegrated HIV-1 suppressive activity during monocyte-T cell interactions might protect against the establishment of infection by limiting viral dissemination.

CD4-Positive T-Lymphocytes↗

PubMed2001

Viral load differences in early infection with two HIV-1 subtypes.

OBJECTIVES: Information on early HIV-1 infection has come primarily from studies of persons infected with subtype B in North America and Europe; much less is known about other subtypes. The purpose of the present study was to compare the virologic and immunologic parameters following seroconversion among recently-infected persons infected with either of two different HIV-1 subtypes. METHOD: A prospective cohort study was carried out at methadone treatment clinics administered by the Bangkok Metropolitan Administration, Thailand. A total of 130 HIV-1-infected seroconverters (103 with HIV-1 subtype E and 27 with subtype B) were included in the study. The main outcome measures were serial HIV-1 RNA viral load, natural killer cell percentage, CD4 and CD8 lymphocyte counts since seroconversion. RESULTS: The demographic and behavioral characteristics of persons with either subtype were similar. Median RNA viral levels at the earliest time within 3 months of seroconversion were more than three times higher for persons infected with subtype E than subtype B (63 100 versus 18 050 copies/ml, P = 0.001). However, this difference decreased over time such that viral loads were similar at 12, 18, and 24 months following seroconversion. The CD4 and CD8 lymphocyte counts were similar in infections with either subtype during the entire period up to 24 months post-seroconversion. CONCLUSIONS: Higher viral loads associated with subtype E may result from inter-subtype biological differences; however, the epidemiological dynamics of transmission in Bangkok may have also contributed to this phenomenon.

Adult↗

PubMed2001

Evaluation of a sensitive/less-sensitive testing algorithm using the 3A11-LS assay for detecting recent HIV seroconversion among individuals with HIV-1 subtype B or E infection in Thailand.

The development of a serologic algorithm to determine recent HIV seroconversion, using sensitive/less-sensitive testing strategies, has generated widespread interest in applying this approach to estimate HIV-1 incidence in various populations around the world. To evaluate this approach in non-B subtypes, longitudinal specimens (n = 522) collected from 90 incident infections among injecting drug users in Bangkok (subtype B infection, n = 18; subtype E infection, n = 72) were tested by the 3A11-LS assay. Standardized optical density (SOD) was calculated, using median values, and the window period between seroconversion as determined by sensitive and less sensitive tests was estimated by a maximum-likelihood model described previously. Our results show that the mean window period of the 3A11-LS assay was 155 days (95% CI, 128-189 days) for subtype B but was 270 days (95% CI, 187-349 days) for subtype E specimens from Thailand. About 4% of individuals with incident subtype E infections remained below the threshold (SOD of 0.75), even 2 years after seroconversion. Among the patients with clinical AIDS and declining antibodies, none of the 7 individuals with subtype B, but 10 (8.7%) of 115 with subtype E infections, were misclassified as recent infections. Lowering the cutoff to an SOD of 0.45 for subtype E specimens resulted in a mean window period of 185 days (95% CI, 154-211 days), with all individuals seroconverting, and reduced the number of subtype E-infected patients with AIDS who were misclassified as having recent infection to 2.6%. Our results demonstrate that the 3A11-LS assay has different performance characteristics in detecting recent infections among individuals infected with subtypes B or E. Determining appropriate cutoffs and mean window periods for other HIV-1 subtypes will be necessary before this approach can be reliably implemented in settings where non-B subtypes are common.

Adult↗

PubMed2001

Continued high HIV-1 incidence in a vaccine trial preparatory cohort of injection drug users in Bangkok, Thailand.

BACKGROUND: A large epidemic of HIV-1 subtype B began among injection drug users (IDUs) in Bangkok in 1988. Despite ongoing prevention efforts, HIV-1 prevalence among IDUs remained at 30-50% through the 1990s. OBJECTIVES: To measure the incidence of HIV-1 infection and related risk factors to guide prevention efforts and to evaluate the feasibility of conducting an HIV vaccine efficacy trial. DESIGN AND METHODS: A prospective cohort study in which IDUs attending methadone treatment programs in Bangkok were screened during 1995-1996 for enrollment into the study. IDUs found to be HIV-seronegative on two occasions were offered enrollment with follow-up visits every 4 months. On each visit participants were evaluated with a questionnaire and serologic testing. RESULTS: A total of 1209 HIV-negative IDUs were enrolled. Through the end of 1998, the overall HIV-1 incidence rate was 5.8 (95% confidence interval, 4.8-6.8) per 100 person-years of follow-up. HIV-1 subtypes E and B accounted for 79 and 21% of infections, respectively. On multivariate analysis, HIV-1 seroconversion was primarily associated with the frequency of heroin injection, the sharing of injection equipment, and incarceration, especially with drug injection. Sexual behavior was not associated with increased risk for HIV-1. Risk factors for infection with HIV-1 subtypes E and B were similar. CONCLUSION: HIV-1 transmission risk remains high among Bangkok IDUs despite methadone treatment and other current prevention strategies. There is an urgent need to address this ongoing epidemic, especially in jails and prisons. This study led to the initiation in 1999 of a phase III HIV-1 vaccine efficacy trial in this population.

AIDS Vaccines↗

PubMed2001

Rapid assessment of sexual behavior, drug use, human immunodeficiency virus, and sexually transmitted diseases in northern thai youth using audio-computer-assisted self-interviewing and noninvasive specimen collection.

BACKGROUND: Drug use, unwanted pregnancy, human immunodeficiency virus (HIV) infection, and sexually transmitted diseases are serious health problems among Thai youth. The gravity of these problems demands high-quality data to direct public health policy and prevention programs. Previous studies of stigmatized behaviors have been hampered by participation bias and underreporting. To evaluate sexual behavior, disease, and drug use, we used audio-computer-assisted self-interviewing (ACASI) and noninvasive specimen collection methods. We also evaluated effectiveness of these methods in minimizing participation bias and underreporting. METHODS: In late 1999, students aged 15 to 21 years attending 3 vocational schools were invited to participate in a cross-sectional survey. Consenting students completed a classroom-based ACASI interview using a confidential code number system. Oral fluid specimens were tested for HIV antibodies, and urine was tested for chlamydial and gonococcal nucleic acids, methamphetamines, and opiates. RESULTS: Of 1736 invited students, 1725 (99%) agreed to participate. Of these, 48% of the male students and 43% of the female students reported ever having had sexual intercourse. Overall, the mean number of lifetime sexual partners was 4.6 among male participants (median: 2) and 2.8 among female participants (median: 1). Consistent use of condoms with steady partners was reported by 16% of male participants and 11% of female participants who had such partners. Of all male participants, 7% had ever paid for sex, 3% had ever sold sex, and 7% had ever been coerced to have sex. Of all female participants, 3% had ever sold sex and 21% had ever been coerced to have sex. Among women with a history of sexual intercourse, 27% reported at least 1 pregnancy. Of these pregnancies, 83% were terminated. Among those with sexual intercourse experience, the prevalence of HIV infection was 0.5%; of infection with Neisseria gonorrhoeae, 0.4%; and of infection with Chlamydia trachomatis, 5%. Twenty-nine percent of students reported ever having used methamphetamines. Ten percent had a methamphetamine-positive urine test. In the ACASI interview, 16% of these denied ever having used methamphetamines. The prevalence of opiate positive urine tests was low (0.2%). CONCLUSION: This study shows that adolescents and young adults in Chiang Rai are at high risk for having unprotected intercourse, being coerced to have sex, unwanted pregnancy, sexually transmitted diseases, and drug use. The high enrollment rate demonstrates the feasibility and acceptability of using ACASI and noninvasive specimen collection methods in a developing country. ACASI use may lead to increased, but not to complete, self-reporting of sensitive behaviors.

Adolescent↗

PubMed2000

Early diagnosis of HIV-1-infected infants in Thailand using RNA and DNA PCR assays sensitive to non-B subtypes.

OBJECTIVES: To evaluate the sensitivity and specificity of RNA and DNA polymerase chain reaction (PCR) for early diagnosis of perinatal HIV-1 infection and to investigate early viral dynamics in infected infants. DESIGN: A cohort study of 395 non-breastfed infants born to HIV-infected mothers in a randomized clinical trial of short-course antenatal zidovudine. METHODS: Infant venous blood specimens collected at birth, 2 months, and 6 months of age were tested by qualitative DNA and quantitative RNA PCR (Roche Amplicor). To determine sensitivity and specificity of DNA and RNA PCR, results were compared with later DNA PCR results and to antibody results at 18 months. The HIV-1 subtype of the mother's infection was determined by peptide serotyping. RESULTS: In the study, 92% of mothers were infected with subtype E. DNA PCR sensitivity was 38% (20 of 53) at birth, and 100% at 2 months (53 of 53) and 6 months (47 of 47). RNA PCR sensitivity was 47% (25 of 53) at birth and 100% (53 of 53) at 2 months. All samples that tested DNA-positive tested RNA-positive. Specificity was 100% for both DNA and RNA testing at all timepoints. For infected infants, the median viral load of RNA-positive specimens was 407,000 copies/ml (5.6 log10) at birth, 3, 700,000 copies/ml (6.6 log10) at 2 months, and 1,700,000 copies/ml (6.2 log10) at 6 months. Infant RNA levels at 2 and 6 months did not differ by maternal zidovudine exposure, or RNA level at birth. CONCLUSION: This RNA PCR assay performed well for diagnosing perinatal HIV subtype E infection, detecting nearly half of infected infants at birth, and 100% at 2 and 6 months, with 100% specificity. Infected infant viral RNA levels were very high at 2 and 6 months, and were unaffected by maternal zidovudine treatment.

Age Factors↗

PubMed2000

Genetic characterization of incident HIV type 1 subtype E and B strains from a prospective cohort of injecting drug users in Bangkok, Thailand.

We obtained specimens from 128 HIV-1 seroconverters identified from 1995 through 1998 in a prospective cohort study of 1,209 HIV-negative injecting drug users (IDUs) in Bangkok, Thailand. Epidemiologic data indicated that parenteral transmission accounted for nearly all infections. HIV-1 DNA from the C2-V4 env region was sequenced, and phylogenetic analyses determined that 102 (79.7%) of the specimens were subtype E and 26 (20.3%) subtype B strains. All subtype B strains clustered with strains often referred to in previous studies as Thai B or B'. The interstrain nucleotide distance (C2-V4) within subtype E strains was low (mean, 6.8%), and pairwise comparisons with a prototype subtype E strain, CM244, showed limited divergence (mean, 5.6%). The subtype B stains showed greater interstrain divergence (mean, 9.2%) and were significantly divergent from the prototype B strain HIV-MN (mean, 13.0%; p < 0.0001). The subtype E strains had significantly lower mean V3 loop charge than did subtype B strains (p = 0.017) and, on the basis of analysis of amino acid sequences, were predicted to be predominantly (91%) non-syncytium-inducing (NSI), chemokine coreceptor CCR5-using (CCR5+) viruses. The subtype B strains had a higher mean V3 loop charge, and a smaller proportion (23%) were predicted to be NSI/CCR5+ viruses. This study demonstrates that most incident HIV1 infections among Bangkok IDUs are due to subtype E viruses, with a narrow spectrum of genetic diversity. The characterization of incident HIV-1 strains from 1995 to 1998 will provide important baseline information for comparison with any breakthrough infections that occur among IDUs in Bangkok who are participating in an HIV-1 vaccine efficacy trial initiated in 1999.

Amino Acid Sequence↗