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W L Heyward

Publications and source records attributed to W L Heyward.

At least 19 recordsLinked to original sources
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↗
PubMed2000

AIDSVAX (MN) in Bangkok injecting drug users: a report on safety and immunogenicity, including macrophage-tropic virus neutralization.

A randomized, double-blind, placebo-controlled phase I/II study of AIDSVAX (MN) was conducted among injecting drug users in Bangkok, Thailand. Four doses of vaccine (300 microg of MN-rgp120 in alum) or placebo (alum) were given at study entry and at 1, 6, and 12 months. The objectives of the study were to evaluate (1) the feasibility of conducting vaccine trials in this population; (2) the safety of this candidate AIDS vaccine; and (3) the immunogenicity of this vaccine. Thirty-three volunteers (22 vaccine and 11 placebo recipients) were recruited. None were lost to follow-up during the 18-month study. Mild reactogenicity was noted, which was similar in both vaccine and placebo recipients. The vaccine induced anti-HIV-1 antibody in all vaccine recipients. Maximal titers of binding antibodies of MN-rgp120 and the V3 domain of MN-rgp120 were induced after the third (6 month) dose while maximal neutralizing antibodies followed the fourth (12 month) dose. The vaccine-induced antibodies from several volunteers were capable of neutralizing macrophage-tropic, subtype B viruses (301660 and JRCSF) detected in a PBMC-based assay. Binding and neutralizing antibodies declined about 10-fold in the 6 months after the last boost. Two vaccinees became infected during the trial, both with subtype E viruses. A phase III efficacy trial, using a bivalent gp120 vaccine containing antigens from a subtype B virus (MN) and a subtype E virus (A244), was initiated in March 1999 in injecting drug users in Bangkok.

AIDS Vaccines↗
PubMed1999

Willingness of injection drug users to participate in an HIV vaccine efficacy trial in Bangkok, Thailand.

We assessed willingness to participate in an HIV recombinant gp120 bivalent subtypes B/E candidate vaccine efficacy trial among 193 injection drug users (IDUs) attending drug treatment clinics in Bangkok, Thailand. IDUs previously enrolled in a prospective cohort study were invited to group sessions describing a potential trial, then completed questionnaires assessing comprehension and willingness to participate. A week later, they completed a follow-up questionnaire that again assessed comprehension and willingness to participate, as well as barriers to and positive motives for participation, with whom (if anyone) they talked about the information, and whether others thought participation was a good, bad, or neutral idea. At baseline, 51% were definitely willing to participate, and at follow-up 54%; only 3% were not willing to participate at either time. Comprehension was high at baseline and improved at follow-up. Participants who viewed altruism, regular HIV tests, and family support for participation as important were more willing to volunteer. Frequency of incarceration and concerns about the length of the trial, possible vaccine-induced accelerated disease progression, and lack of family support were negatively associated with willingness. Overall, IDUs comprehended the information needed to make a fully informed decision about participating in an rgp120 vaccine efficacy trial and expressed a high level of willingness to participate in such a trial.

AIDS Vaccines↗
PubMed1998

Infection with HIV-1 subtypes B and E in injecting drug users screened for enrollment into a prospective cohort in Bangkok, Thailand.

From May through August 1995, a cross-sectional survey was conducted among injecting drug users (IDUs) drawn from 15 drug treatment clinics in Bangkok and who were not known to be HIV-seropositive, to determine the prevalence of HIV-1 subtypes B and E and related risk behaviors, and to offer enrollment in a prospective cohort study. IDUs who voluntarily consented were interviewed, and blood specimens were tested for the presence of HIV antibodies. HIV-1-seropositive specimens were tested for subtypes B' (Thai B) and E by using V3 loop peptide enzyme immunoassays specific for these HIV-1 genetic subtypes. Of 1674 IDUs studied, the mean age was 31.2 years (interquartile range, 25-37 years), 94.8% were men, and 29.3% were HIV-1-seropositive. On multiple logistic regression analysis, HIV-1 seropositivity was associated with older age, not being married, less education, needle sharing, and incarceration. HIV-1 subtype B' accounted for 65% of prevalent infections and subtype E, 35%. Infection with subtype E was associated with younger age and did not seem to be associated with sexual risk behaviors, which were uncommon in general. Bangkok IDUs continue to be at high risk for HIV-1 infection related to needle sharing and incarceration. Although HIV-1 subtype B' accounts for most prevalent infections, subtype E seems to be more prevalent among younger IDUs, and most infections seem likely to result from parenteral transmission.

Adult↗
PubMed1998

HIV vaccine development and evaluation: realistic expectations.

As of January 1998, more than 85 vaccines for 24 clinical indications are currently licensed in the United States. From the time of discovery of the etiologic agent to the development of a licensed vaccine, many years have usually been required. Although many vaccines have been licensed on the basis of one efficacy trial, multiple vaccine concepts and multiple efficacy trials (both in the United States and internationally) have at times been necessary. Over a relatively short period of time, there has been remarkable progress in human immunodeficiency virus (HIV) vaccine development, with over 34 different HIV candidate vaccines having been tested in phase 1 trials, and three having been tested in phase 2 trials. In spite of our incomplete understanding of HIV pathogenesis and correlates of protection, the first phase 3 efficacy trial has been initiated in the U.S. and tentative plans have been announced for three other phase 3 efficacy trials with the most advanced HIV candidate vaccines to begin in the next 3 years. Like many previous vaccine development efforts, these initial HIV vaccine efficacy trials could be the first of many large-scale efficacy trials in the future, testing various vaccine design concepts among different high-risk populations in both developed and developing countries. The choice of when and how to proceed to phase 3 trials remains a complex decision, but it is likely that only through such trials will further knowledge be gained to advance this important effort and reach our goal of a safe and effective HIV vaccine.

AIDS Vaccines↗
PubMed1995

HIV preventive vaccines. Progress to date.

The major conceptual problem for HIV vaccine development has been the lack of information on immune responses known to correlate with protection against HIV infection in humans. In this regard, studies on the natural history of HIV infection and AIDS, especially of people with apparent resistance to HIV infection and of patients with HIV infection who have long term survival without disease progression, may provide important information for vaccine development. In addition, a major concern for the development of broadly effective vaccines has been the extensive genetic variability which is characteristic of HIV. In spite of these unknowns, the first generation of HIV candidate vaccines has been developed and evaluated. HIV candidate vaccines based on the subunit recombinant envelope concept (gp120 or gp160) have been shown to protect chimpanzees from HIV infection on challenge, and have now been evaluated in humans in phase I and phase II trials. These products are well tolerated, and capable of inducing neutralising antibodies, but not cytotoxic T lymphocytes. A second vaccine concept, currently in phase I trials, is based on live recombinant vectors, especially using poxvirus vectors followed by boosting with subunit recombinant envelope vaccines. This concept is theoretically very attractive because preliminary data suggest that these vaccines induce both humoral and cell-mediated immunity. However, no published information is available on the ability of live recombinant vector vaccines to protect chimpanzees from HIV infection. The next step in HIV vaccine development is to proceed carefully to expanded phase II and phase III trials to assess the protective efficacy of these candidate vaccines in humans. These trials will be extremely complex from the logistical, scientific and ethical points of view, and will require close collaboration between clinical, basic science and behavioural researchers, national and international organisations, and the pharmaceutical industry.

AIDS Vaccines↗
PubMed1994

Elevated concentrations of plasma omega-3 polyunsaturated fatty acids among Alaskan Eskimos.

Eskimos living in rural southwestern Alaska depend on fish and marine mammals as major sources of subsistence food. Fatty acid concentrations in 80 Yupik Eskimos living in either a coastal or river village of southwestern Alaska were compared with those of non-Native control subjects. Concentrations of total plasma omega-3 fatty acids, eicosapentaenoic acid (20:5 omega-3), and docosahexaenoic acid (22:6 omega-3) were 4.3, 13, and 6.8 times higher, respectively, in Native participants than in non-Native control subjects. Concentrations of these fatty acids were higher in coastal-village than in river-village participants; concentrations paralleled consumption of marine mammal oil and marine fish. The ratios of eicosapentaenoic to arachidonic acid for adult coastal- and river-village participants were 1.16 and 0.70, respectively, 14 and 9 times those of non-Native adults, respectively. There was no increase in the mean bleeding times of Native participants of either village.

Adolescent↗
PubMed1994

Mortality in HIV-1-seropositive women, their spouses and their newly born children during 36 months of follow-up in Kinshasa, Zaïre.

OBJECTIVE: To calculate 3-year mortality rates in HIV-1-seropositive and HIV-1-seronegative mothers, their newborn children and the fathers of these children. DESIGN: Longitudinal cohort study of HIV-1-seropositive, age and parity-matched HIV-1-seronegative pregnant women, their newborn babies and the fathers of these children. SETTING: Obstetric ward and follow-up clinic at a large municipal hospital in Kinshasa, Zaïre. PARTICIPANTS: A total of 335 newborn children and their 327 HIV-1-seropositive mothers and 341 newborn children and their 337 HIV-1-seronegative mothers and the fathers of these children. MAIN OUTCOME MEASURES: Rates of vertical HIV-1 transmission and maternal, paternal and early childhood mortality. RESULTS: The lower and upper bounds of vertical transmission were 27 and 50%, respectively. The 3-year mortality rate was 44% in children with vertically acquired HIV-1 infection, 25% in children with HIV-1-seropositive mothers and indeterminant HIV-1 infection status, and 6% in uninfected children with HIV-1-seronegative mothers. HIV-1-seropositive women who transmitted HIV-1 infection to their most recently born child had lost a greater number of previously born children (mean, 1.5 versus 0.5; P < 0.05), were more likely to have had AIDS at delivery (25 versus 12%; P < 0.01) and were more likely to die during follow-up (22 versus 9%; P < 0.01) than HIV-1-seropositive women who did not transmit HIV-1 infection to their newborn child. Twenty-five out of 239 (10.4%) fathers of children with HIV-1-seropositive mothers, not lost to follow-up, died compared with three out of 310 (1%) fathers of children with HIV-1-seronegative mothers (P < 0.01). CONCLUSIONS: Families in Kinshasa, Zaïre, in which the mother was HIV-1-seropositive experienced a five to 10-fold higher maternal, paternal and early childhood mortality rate than families in which the mother was HIV-1-seronegative.

Acquired Immunodeficiency Syndrome↗
PubMed1994

AIDS orphans in Kinshasa, Zaïre: incidence and socioeconomic consequences.

OBJECTIVE: To determine the incidence, morbidity, mortality, and socioeconomic consequences of becoming an AIDS orphan (a child with an HIV-1-seropositive mother who has died) in Kinshasa, Zaïre. DESIGN: A longitudinal cohort study was undertaken between 1986 and 1990. Within this cohort, a nested case-control study of AIDS orphans was performed. AIDS orphan cases were children with an HIV-1-seropositive mother who had died. Two groups of control children were identified. The first group of control children were age-matched children with HIV-1-seropositive mothers who were alive at the time of death of the AIDS orphan case mother. The second group of control children were children with HIV-1-seronegative mothers who were also alive at the time of death of the AIDS orphan case mother. SETTING: Obstetric ward and follow-up clinic at two large municipal hospitals in Kinshasa, Zaïre. PARTICIPANTS: A total of 466 HIV-1-seropositive women, their children, and the fathers of these children; 606 HIV-1-seronegative women, their children, and the fathers of these children. MAIN OUTCOME MEASURES: AIDS orphan incidence, HIV-1 vertical transmission rate, morbidity, mortality and socioeconomic indicators of the consequences of becoming an AIDS orphan. RESULTS: The AIDS orphan incidence rate was 8.2 per 100 HIV-1-seropositive women-years of follow-up. Vertical transmission of HIV-1 was higher in AIDS orphan cases (41%) than in control children with HIV-1-seropositive mothers (26%; P < 0.05). Among children without vertically acquired HIV-1 infection, morbidity rates and indices of social and economic well-being were similar in AIDS orphans and control children. Five out of 26 (19%) AIDS orphan cases died during follow-up, compared with three out of 52 (6%) control children (P < 0.05). CONCLUSION: During a 3-year follow-up period, children with HIV-1-seropositive mothers had a considerable risk of becoming an AIDS orphan. However, the presence of a concerned extended family appeared to minimize any adverse health and socioeconomic effects experienced by orphan children.

Acquired Immunodeficiency Syndrome↗
PubMed1994

High HIV-1 incidence in young women masked by stable overall seroprevalence among childbearing women in Kinshasa, Zaïre: estimating incidence from serial seroprevalence data.

OBJECTIVE: To describe the dynamics of the HIV-1 epidemic in childbearing women in Kinshasa, Zaïre, by estimating incidence from serial seroprevalence studies. METHODS: In 1986 and 1989, 5937 and 4623 pregnant women, respectively, were screened for HIV-1 in Kinshasa. We estimated age-specific incidence from two seroprevalence surveys by using a birth-year cohort analysis and adjusting for differences in mortality and fertility between HIV-1-infected and uninfected women. Mortality and fertility data were measured in a cohort of women recruited from the survey in 1986 and followed until 1989. RESULTS: While the overall HIV-1 seroprevalence changed little (5.8% in 1986 and 6.5% in 1989; P = 0.17), the prevalence increased in birth-year cohorts of women under 25 years of age in 1989 from 3.2 to 6.2% (P < 0.001), but decreased for women above 25 years of age from 6.9 to 6.7% (P = 0.7). In addition, new HIV infections between 1986 and 1989 were balanced by a higher mortality and lower fertility observed in HIV-infected women. After adjusting for these effects, we estimated an overall 3-year cumulative HIV-1 incidence of 2.8 per 100 uninfected women [95% confidence interval (CI), 1.4-4.2]. The highest incidence, 5.7 per 100 (95% CI, 3.5-8.0), was in women aged 20-24 years in 1989. CONCLUSION: Despite an overall relatively stable HIV-1 prevalence in childbearing women in Kinshasa between 1986 and 1989, approximately 40% of all HIV-1 infections detected in the 1989 survey occurred between 1986 and 1989, and 60% occurred in women under 25 years of age in 1989.

Adult↗
PubMed1994

Preparation for phase III HIV vaccine efficacy trials: methods for the determination of HIV incidence.

OBJECTIVE: Accurate estimates of HIV incidence that reflect the effect of non-vaccine interventions (education, counselling, condom promotion, and possibly sexually transmitted disease treatment) and that may be provided in a Phase III vaccine efficacy trial, are needed so that vaccine trial population sample sizes can be accurately determined. In order to avoid delays in the implementation of efficacy trials, well characterized cohorts must also be developed and available to participate in such trials. We reviewed the potential study populations, the epidemiologic methods for the determination of HIV incidence (using open cohort, closed cohort, and seroprevalence data methods), and the need for the development of population cohorts in preparation for Phase III HIV vaccine efficacy trials. SETTING: Phase III trials in developed and developing countries. METHODS: Comparison of open and closed cohorts and those using seroprevalence data to estimate HIV incidence. RESULTS: Open and closed cohorts each have disadvantages and advantages. However, the open cohort may be more suitable for determining estimates of HIV incidence that reflect non-vaccine interventions and for the development of a well characterized cohort available to participate in efficacy trials. CONCLUSION: Careful preparation of research infrastructures and population cohorts will help ensure the successful conduct of scientifically and ethically sound HIV vaccine efficacy trials in the future.

AIDS Vaccines↗
PubMed1994

Lack of association between anti-V3 loop antibody and perinatal HIV-1 transmission in Kinshasa, Zaire, despite use of assays based on local HIV-1 strains.

Maternal antibodies against the V3 loop principal neutralizing domain (PND) have been reported to protect against perinatal HIV-1 transmission. To study this association in an African city with a long-standing HIV epidemic and no established "consensus sequence" for the V3 loop region of gp120, we determined the DNA sequence for the V3 region of HIV-1 from 13 HIV-1-infected residents of Kinshasa, Zaire, and developed peptide enzyme immunoassays (EIAs) reflecting the V3 loop PND for those HIV-1 strains. Using the most broadly reactive locally derived V3 loop peptide in a limited-antigen EIA, there was no significant difference in the perinatal HIV-1 transmission risk between 64 women with anti-V3 loop antibody (transmission risk, 30%) and 104 women without anti-V3 loop antibody (transmission risk, 25%; p = 0.5); this finding was unchanged after we controlled for maternal AIDS and low birth weight. Although we used assays for V3 loop antibody based on local HIV-1 strains and evaluated a large number of mother-child pairs, we found no evidence that maternal anti-V3 loop PND antibody protects against perinatal HIV-1 transmission.

Amino Acid Sequence↗
PubMed1993

Genital types of papillomavirus in children of women with HIV-1 infection in Kinshasa, Zaire.

Increasing evidence indicates that infection with genital types of human papillomavirus (HPV) can occur prior to the onset of sexual activity, possibly by perinatal transmission. Evidence is also accumulating that women infected with the human immunodeficiency virus (HIV) more frequently express HPV. We conducted this study to measure HPV prevalence in HIV-seropositive and -seronegative women in Kinshasa, Zaire and in their children. We collected cervico-vaginal lavage specimens from 80 mothers (52 HIV-seropositive and 28 HIV-seronegative at the time of delivery) and oropharyngeal and perineal specimens from their 81 3-year old children (21 HIV-seropositive and 60-seronegative). We used the ViraPap and ViraType assay to test specimens for HPV DNA by the dot-blot technique. Detection of HPV in the mother was highly associated with HIV: 20 HIV-seropositive women and one seronegative woman had HPV DNA. Ten children had HPV DNA. However, detection of HPV in the children was not associated with the mothers' HPV or HIV status or with the child's own HIV status. These findings document a substantial prevalence in young children of HPV DNA types that are linked to genital-tract neoplasia in adults, but do not specifically support a hypothesis of mother-to-child transmission of genital HPV types.

DNA, Viral↗