Vaccine Preparedness Research Articles

Trends in HIV-1 incidence in a cohort of prostitutes in Kenya: implications for HIV-1 vaccine efficacy trials.

Accurate predictions of HIV-1 incidence in potential study populations are essential for designing HIV-1 vaccine efficacy trials. Little information is available on the estimated incidence of HIV-1 in such populations, especially information on incidence over time and incidence while participating in risk-reduction programs. To examine time trends in HIV-1 incidence in a vaccine preparedness cohort. Prospective cohort study of female prostitutes in Mombasa, Kenya. HIV-1 incidence was determined using open and closed cohort designs. Generalized estimating equations were used to model HIV-1 and sexually transmitted disease (STD) incidence and sexual risk behaviors over time. When analyzed as a closed cohort, HIV-1 incidence declined 10-fold during 3 years of follow-up (from 17.4 to 1.7 cases/100 person-years; p <.001). More than 50% of the cases of HIV-1 occurred during the first 6 months after enrollment, and 73% during the first 12 months. When analyzed as an open cohort, HIV-1 incidence density fell during the first 4 calendar years, influenced by accumulation of lower risk participants and variations in study recruitment. Significant declines occurred in both STD incidence and high-risk sexual behaviors during follow-up. This study documents a dramatic decline in the risk of HIV-1 infection while participating in a prospective cohort, with most seroconversions occurring within 1 year of enrollment. Variations in HIV-1 incidence within high-risk populations should be anticipated during the design of vaccine trials.

Use of reality "female condoms" for anal sex by US men who have sex with men. HIVNET Vaccine Preparedness Study Protocol Team.

This study assessed use of Reality "female condoms" for anal sex by HIV-seronegative men who have sex with men and are at high risk for HIV infection. Self-administered questionnaires were completed by 2277 participants in a 6-city prospective cohort study. Of the 1084 (48%) men who had heard of using the female condom for anal sex, 145 (13%) reported using it in the prior 6 months. Users were at greater risk than nonusers: 47 receptive and 35 insertive users reported problems, including bleeding by the receptive partner (4). Redesign of the female condom could increase acceptability and use by men who have sex with men and could address possible safety concerns.

A mouse model for the evaluation of pathogenesis and immunity to influenza A (H5N1) viruses isolated from humans.

During 1997 in Hong Kong, 18 human cases of respiratory illness, including 6 fatalities, were caused by highly pathogenic avian influenza A (H5N1) viruses. Since H5 viruses had previously been isolated only from avian species, the outbreak raised questions about the ability of these viruses to cause severe disease and death in humans. To better understand the pathogenesis and immunity to these viruses, we have used the BALB/c mouse model. Four H5N1 viruses replicated equally well in the lungs of mice without prior adaptation but differed in lethality for mice. H5N1 viruses that were highly lethal for mice were detected in multiple organs, including the brain. This is the first demonstration of an influenza A virus that replicates systemically in a mammalian species and is neurotropic without prior adaptation. The mouse model was also used to evaluate a strategy of vaccination against the highly pathogenic avian H5N1 viruses, using an inactivated vaccine prepared from nonpathogenic A/Duck/Singapore-Q/F119-3/97 (H5N3) virus that was antigenically related to the human H5N1 viruses. Mice administered vaccine intramuscularly, with or without alum, were completely protected from lethal challenge with H5N1 virus. Protection from infection was also observed in 70% of animals administered vaccine alone and 100% of mice administered vaccine with alum. The protective effect of vaccination correlated with the level of virus-specific serum antibody. These results suggests a strategy of vaccine preparedness for rapid intervention in future influenza pandemics that uses antigenically related nonpathogenic viruses as vaccine candidates.

Correlates of condom failure in a sexually active cohort of men who have sex with men.

Condom failure (slippage or breakage) has been shown to be associated with HIV seroconversion among men who have sex with men (MSM), but predictors of failure have been poorly elucidated. Of 2592 HIV-seronegative MSM participants in the HIV Network for Prevention Trials (HIVNET) multisite Vaccine Preparedness Study who reported condom use for anal sex in the 6 months before enrollment, condom failure was reported by 16.6%, with failure rates of 2.1/100 episodes of condom usage (2.5 failures/100 episodes for receptive anal sex and 1.9/100 episodes for insertive anal sex). In separate multivariate models evaluating predictors of condom failure reported by the insertive and receptive partners, more frequent condom use was associated with a decreased per-condom failure rate and amphetamine and heavy alcohol use with increased rates in both models. Being employed, having private medical insurance, and using lubricants for >80% of anal sex acts were significantly associated with decreased failure rates in the insertive model. Safer sex counseling should particularly target men of lower socioeconomic status, promote proper and consistent use of condoms with appropriate lubricants, and address the impact of drug use, especially amphetamines and alcohol, on condom failure.

HIV incidence among injecting drug users in New York City syringe-exchange programmes

There have been no studies showing that participation in programmes which provide legal access to drug-injection equipment leads to individual-level protection against incident HIV infection. We have compared HIV incidence among injecting drug users participating in syringe-exchange programmes in New York City with that among non-participants. We used meta-analytic techniques to combine HIV incidence data from injecting drug users in three studies: the Syringe Exchange Evaluation (n = 280), in which multiple interviews and saliva samples were collected from participants at exchange sites; the Vaccine Preparedness initiative cohort (n = 133 continuing exchanges and 188 non-exchangers, in which participants were interviewed and tested for HIV every 3 months; and very-high-seroprevalence cities in the National AIDS Demonstration Research (NADR) programme (n = 1029), in which street-recruited individuals were interviewed and tested for HIV every 6 months. In practice, participants in the NADR study had not used syringe exchanges. HIV incidence among continuing exchange-users in the Syringe Exchange Evaluation was 1.58 per 100 person-years at risk (95% CI 0.54, 4.65) and among continuing exchange-users in the Vaccine Preparedness Initiative it was 1.38 per 100 person-years at risk (0.23, 4.57). Incidence among non-users of the exchange in the Vaccine Preparedness Initiative was 5.26 per 100 person-years at risk (2.41, 11.49), and in the NADR cities, 6.23 per 100 person-years at risk (4.4, 8.6). In a pooled-data, multivariate proportional-hazards analysis, not using the exchanges was associated with a hazard ratio of 3.35 (95% CI 1.29, 8.65) for incident HIV infection compared with using the exchanges. We observed an individual-level protective effect against HIV infection associated with participation in a syringe-exchange programme. Sterile injection equipment should be legally provided to reduce the risk of HIV infection in persons who inject illicit drugs.

Will Preventive HIV Vaccine Efficacy Trials Be Possible With Female Injection Drug Users?

This article examines whether preventive HIV vaccines trials will be viable among female injection drug users (IDUs). Of the 137 women who completed baseline serologic and behavioral assessments, 121 (88%) were seronegative; all enrolled in Project Jumpstart in Philadelphia (PA, U.S.A.), a vaccine preparedness initiative cosponsored by NIAID and NIDA. Subjects were seen every 3 months for risk and vaccine opinion assessment, risk reduction counseling, and HIV antibody testing. The baseline prevalence rate of HIV infection was 12% (16 of 137) with an annual incidence rate of 3.5% (4 of 114) during the first year. Of the 121 baseline seronegative women, 28% shared needles and 52% engaged in unprotected intercourse. Sixty percent of the baseline seronegative women reported being willing to be one of the first people to try an HIV vaccine. According to logistic regression, needle sharers were 12.8 times more likely, women who engaged in sex for drugs or money 6.6 times more likely, out-of-treatment women 3.5 times more likely, and those who believed that vaccines can prevent disease acquisition 3 times more likely to report willingness to try an HIV vaccine than their respective counterparts. At 1-year postbaseline assessment, 98% of the women had behavioral data collected and 95% had serologic specimens collected. Given that seroconversions occur and that these women engage in risk behaviors, report willingness to try an HIV vaccine, and can be retained for longitudinal assessment, they appear to be suitable participants for preventive HIV vaccine efficacy trials. Nonetheless, work is required to insure that these women make informed and knowledgeable decisions regarding trial enrollment.

Prevention Research and Vaccine Preparedness: Conference Summary

AIDS Research and Human RetrovirusesVol. 11, No. 10 Prevention Research and Vaccine Preparedness: Conference SummaryConference on Advances in AIDS Vaccine Development—1994LEWELLYS F. BARKER, HAROLD W. JAFFE, and ZEDA F. ROSENBERGLEWELLYS F. BARKERSearch for more papers by this author, HAROLD W. JAFFESearch for more papers by this author, and ZEDA F. ROSENBERGSearch for more papers by this authorPublished Online:16 Mar 2009https://doi.org/10.1089/aid.1995.11.1297AboutSectionsPDF/EPUB ToolsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail FiguresReferencesRelatedDetails Volume 11Issue 10Oct 1995 To cite this article:LEWELLYS F. BARKER, HAROLD W. JAFFE, and ZEDA F. ROSENBERG.Prevention Research and Vaccine Preparedness: Conference Summary.AIDS Research and Human Retroviruses.Oct 1995.1297-1299.http://doi.org/10.1089/aid.1995.11.1297Published in Volume: 11 Issue 10: March 16, 2009PDF download

HIV-1 virion-cell interactions: an electrostatic model of pathogenicity and syncytium formation.

AIDS Research and Human RetrovirusesVol. 10, No. 3 HIV-1 Virion-Cell Interactions: An Electrostatic Model of Pathogenicity and Syncytium FormationLARRY CALLAHANLARRY CALLAHANSearch for more papers by this authorPublished Online:16 Mar 2009https://doi.org/10.1089/aid.1994.10.231AboutSectionsPDF/EPUB ToolsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail FiguresReferencesRelatedDetailsCited ByIn vitro methods for testing antiviral drugsBiotechnology Advances, Vol. 36, No. 3The ins and outs of eukaryotic viruses: Knowledge base and ontology of a viral infection16 February 2017 | PLOS ONE, Vol. 12, No. 2Age and sex or gender (sex/gender) and HIV vaccine preparedness29 October 2015 | Psychology, Health & Medicine, Vol. 21, No. 4Motivators of enrolment in HIV vaccine trials: a review of HIV vaccine preparedness studies4 July 2011 | AIDS Care, Vol. 23, No. 11Rapid Dissociation of HIV-1 from Cultured Cells Severely Limits Infectivity Assays, Causes the Inactivation Ascribed to Entry Inhibitors, and Masks the Inherently High Level of Infectivity of VirionsJournal of Virology, Vol. 84, No. 6Could CD4 Capture by CD8+ T Cells Play a Role in HIV Spreading?Journal of Biomedicine and Biotechnology, Vol. 2010Primary HIV-1 R5 isolates from end-stage disease display enhanced viral fitness in parallel with increased gp120 net chargeVirology, Vol. 379, No. 1Enrollment and Retention of HIV Discordant Couples in Lusaka, ZambiaJAIDS Journal of Acquired Immune Deficiency Syndromes, Vol. 47, No. 1Amino Functionalized Novel Cholic Acid Derivatives Induce HIV-1 Replication and Syncytia Formation in T Cells25 March 2006 | Journal of Medicinal Chemistry, Vol. 49, No. 8The Role of Community Advisory Boards: Involving Communities in the Informed Consent ProcessAmerican Journal of Public Health, Vol. 91, No. 12LFA-1 Expression on Target Cells Promotes Human Immunodeficiency Virus Type 1 Infection and TransmissionJournal of Virology, Vol. 75, No. 2Efficacy of Fusion Peptide Homologs in Blocking Cell Lysis and HIV-Induced Fusion KATHERINE A. SILBURN, DALE A. McPHEE, ANNE L. MAERZ, PANTELIS POUMBOURIOS, ROBERT G. WHITTAKER, ALAN KIRKPATRICK, WAYNE G. REILLY, MICHAEL K. MANTHEY, and CYRIL C. CURTAIN15 March 2009 | AIDS Research and Human Retroviruses, Vol. 14, No. 5Inhibition of HIV-1, HIV-2 and SIV envelope glycoprotein-mediated cell fusion by calmodulinVirus Research, Vol. 50, No. 2Anti-HIV Type 1 Activity of Sulfated Derivatives of Dextrin against Primary Viral Isolates of HIV Type 1 in Lymphocytes and Monocyte-Derived Macrophages CAROLINE M. JAVAN, NIGEL J. GOODERHAM, ROBERT J. EDWARDS, DONALD S. DAVIES, and SUNIL SHAUNAK15 March 2009 | AIDS Research and Human Retroviruses, Vol. 13, No. 10Role of the Amino-Terminal Extracellular Domain of CXCR-4 in Human Immunodeficiency Virus Type 1 EntryVirology, Vol. 231, No. 1Mechanism of Anti-HIV Activity of Negatively Charged Albumins: Biomolecular Interaction with the HIV-1 Envelope Protein gp120Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology, Vol. 11, No. 5Positioning of Positively Charged Residues in the V3 Loop Correlates with HIV Type 1 Syncytium-Inducing Phenotype DHANANJAY BHATTACHARYYA, BERNARD R. BROOKS, and LARRY CALLAHAN15 March 2009 | AIDS Research and Human Retroviruses, Vol. 12, No. 2Inhibition of U-937 membrane-associated cathepsin G by GP 120 (IIIB) and V3 loop-derived peptides from several strains of HIV-17 March 2000 | FEBS Letters, Vol. 367, No. 3Adaptation to persistent growth in the H9 cell line renders a primary isolate of human immunodeficiency virus type 1 sensitive to neutralization by vaccine seraJournal of Virology, Vol. 69, No. 1 Volume 10Issue 3Mar 1994 To cite this article:LARRY CALLAHAN.HIV-1 Virion-Cell Interactions: An Electrostatic Model of Pathogenicity and Syncytium Formation.AIDS Research and Human Retroviruses.Mar 1994.231-233.http://doi.org/10.1089/aid.1994.10.231Published in Volume: 10 Issue 3: March 16, 2009PDF download

Prevention of HIV/AIDS with vaccines

HIV vaccines are urgently needed to help control the relentlessly expanding epidemic. However, the development of a safe and effective vaccine for this rapidly mutating virus which produces life-long infection is elusive. Feasibility of HIV vaccination has been demonstrated by challenge studies in primates and by the presence of neutralizing antibodies which confer passive protection and can be detected in vitro. Given safety considerations, the first vaccines developed have been recombinant subunit vaccines consisting of viral envelope antigens formulated with adjuvants or incorporated into live vectors, such as vaccinia and avipox. Subunit envelope vaccines have proven to be safe and immunogenic in human phase I trials. Two gp120 subunit products are being considered for phase III trials based on ongoing evaluation of data from a phase II trial, primate-challenge studies, and laboratory studies evaluating the breadth, magnitude, and duration of immunogenic responses, including neutralization against recent isolates. Efficacy trials will be large and complex, involving people at high behavioral risk for infection. Baseline studies with recruitment goals of over 10000 people are being sponsored in the USA, with many additional vaccine preparedness studies being sponsored in developing nations by international and national authorities. Because high-risk populations will be recruited for trials of many year's duration, new approaches to trial design and community participation will be needed in order for these trials to succeed. Systems must be in place to ensure that trial participants receive preventive counseling and services to minimize discrimination from vaccine-related seroconversions. Here we document the urgent need for HIV vaccines, provide a brief preclinical and clinical update, and present the plans and considerations for testing HIV vaccine efficacy.