Abstract:
:Preexposure prophylaxis (PrEP) of HIV infection with tenofovir-containing regimens is effective, but plagued by poor adherence in some studies. Options for safe, effective, and acceptable PrEP products, especially for men and women at risk of HIV via receptive anal intercourse (RAI), are needed. We performed a randomized, partially blinded, first-in-human evaluation of four candidate rectal microbicide vehicles-aqueous gel, aqueous fluid, lipid gel, and lipid fluid-to select a prototype for further clinical development. Eight seronegative participants received three doses of each product with each dose separated by at least 2 weeks: one dose was given alone without simulated RAI in clinic, another dose was followed by simulated RAI in clinic, and another dose was self-administered at home in the context of RAI with a partner. Assessments included safety, acceptability, colon histology, ex vivo HIV infectivity of colon tissue explants, and colonic luminal distribution of vehicle and HIV surrogates. Adverse events were all mild and mainly sigmoidoscopy associated. There were minor differences in colon distribution of products and little effect of RAI. Vehicle distribution covered 95% (±7% standard deviation) of the distribution of an HIV surrogate in the colonic lumen. The lipid fluid vehicle increased HIV colon tissue infectability 5-fold [log10 p24 0.68 (95% confidence interval 0.08, 1.28)] and aqueous gel provided 6-fold protection [log10 p24 0.80 (95% confidence interval 0.20, 1.41)] compared to no product baseline. Colon permeability of lipid vehicles was more than 10-fold greater than aqueous vehicles. All products received similar acceptability ratings, though trends favored the gel products. Intensive simultaneous assessment of safety and toxicity, luminal and tissue distribution, ex vivo HIV infectivity, and product acceptability in relevant sexual contexts provided clear differentiation among candidate gels very early in product development. We selected the aqueous gel for further development as a rectal microbicide vehicle.
journal_name
AIDS Res Hum Retrovirusesjournal_title
AIDS research and human retrovirusesauthors
Leyva F,Fuchs EJ,Bakshi R,Carballo-Dieguez A,Ventuneac A,Yue C,Caffo B,Du Y,Torbenson M,Li L,Mullin G,Lee L,Rohan L,Anton PA,Hendrix CWdoi
10.1089/AID.2015.0086subject
Has Abstractpub_date
2015-11-01 00:00:00pages
1089-97issue
11eissn
0889-2229issn
1931-8405journal_volume
31pub_type
杂志文章,随机对照试验abstract::The prevalence of different HIV-1 subtypes in Spain varies by geographic region. In the present study isolates were collected from 72 newly diagnosed individuals in western Andalucia from 2004 to 2006. Viral sequences were amplified and the subtype diversity and prevalence of resistance mutations in the reverse transc...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2008.0051
更新日期:2008-06-01 00:00:00
abstract::Some genomic elements of the multicopy HERV-W endogenous retroviral family have been previously identified in databases. One of them, located on chromosome 7, contains a single complete open reading frame (ORF) putatively encoding an envelope protein. We have experimentally investigated the genomic complexity and codi...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/088922200308738
更新日期:2000-05-20 00:00:00
abstract::The emergence of T cell-tropic, syncytium-inducing (T-tropic/SI) HIV-1 variants from the background of macrophage-tropic, non-syncytium-inducing (M-tropic/NSI) strains is associated with disease progression in infected individuals. HIV89.6 is a primary isolate with a transitional phenotype: like M-tropic strains it re...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1997.13.759
更新日期:1997-06-10 00:00:00
abstract::HIV-infected patients are at increased risk of decreased bone mineral density. Some studies have implicated antiretroviral therapy as a contributor to the decreased bone mineral density seen in treated HIV-1 patients. In this study we explore the interactions between protease inhibitors (PI) and primary human osteobla...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2006.0084
更新日期:2007-02-01 00:00:00
abstract::We used enzyme-linked immunosorbant assay (ELISA) and Western blotting, with "purified" human T-cell leukemia virus I (HTLV-I), to test for HTLV-I antibodies in 2583 plasma samples from 1053 leukemia/lymphoma patients treated at Roswell Park Memorial Institute, mostly between 1972 and 1984, and in 110 sera samples fro...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1990.6.617
更新日期:1990-05-01 00:00:00
abstract::Liver enzyme elevations are frequently seen in patients treated with nevirapine (NVP). Both elevated NVP plasma levels and hepatitis C virus (HCV) infection seem to favor the development of NVP-related liver toxicity. We have examined variation on NVP C(trough) over time, as well as the impact of NVP C(trough) concent...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2005.21.555
更新日期:2005-06-01 00:00:00
abstract::Identifying and monitoring HIV clusters could be useful in tracking the leading edge of HIV transmission in epidemics. Currently, greater specificity in the definition of HIV clusters is needed to reduce confusion in the interpretation of HIV clustering results. We address sampling density as one of the key aspects of...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2014.0173
更新日期:2014-12-01 00:00:00
abstract::Infection with the human immunodeficiency virus (HIV) leads to a progressive immunodeficiency characterized by decreasing levels of CD4+ T lymphocytes. VaxSyn, a vaccine based on the recombinant envelope glycoprotein subunit (rgp160) of HIV-1IIIB, was used to immunize HIV-infected patients to determine whether its adm...
journal_title:AIDS research and human retroviruses
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1089/aid.1998.14.483
更新日期:1998-04-10 00:00:00
abstract::We investigated memory cytotoxic T lymphocyte (CTLm) responses to HIV-1 as a determinant of HIV-1 disease progression, in relation to plasma HIV-1 load and T lymphocyte numbers in a longitudinal study of 14 homosexual men with incident HIV-1 infection. Study participants were selected who exhibited failure of T cell h...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1998.14.1423
更新日期:1998-11-01 00:00:00
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journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/08892220152596551
更新日期:2001-09-20 00:00:00
abstract::HIV-1 Vif, Vpr, and Vpu proteins have a profound effect on efficient viral replication and pathogenesis. This study describes the genotypic characterisation of vif , vpr and vpu from 20 South African HIV-1 subtype C primary isolates, and extensive analysis and comparison of known motifs. All HIV-1 subtype C Vif, Vpr a...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2006.0181
更新日期:2007-02-01 00:00:00
abstract::Changes in neutralizing antibody (NA) titers in stored sera collected over 5 years from 10 participants in the Multicenter AIDS Cohort Study (MACS) were evaluated. The participants were HIV-1 infected on enrollment in the MACS, and remained AIDS free during the 5-year study interval. Seven viruses derived from molecul...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章,多中心研究
doi:10.1089/aid.1998.14.939
更新日期:1998-07-20 00:00:00
abstract::HIV-1 group N (HIV-1/N) remains rare and mainly restricted to Cameroon. In this study, we report a new HIV-1/N infected case identified during routine HIV screening activities in Yaounde. The genetic characterization of the near full-length genome of this virus strain revealed that it is genetically distinct to all HI...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/AID.2018.0015
更新日期:2018-07-01 00:00:00
abstract::In the context of an emerging aging epidemic affecting people living with HIV (PLWH), we critically discuss existing data regarding two different conceptual models of aging-frailty and intrinsic capacity, respectively, both in a clinical and public health perspective. These constructs have not yet been integrated in t...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章,评审
doi:10.1089/AID.2019.0157
更新日期:2019-11-01 00:00:00
abstract::Data reporting sexually transmitted infection (STI) incidence rates among HIV-negative U.S. men who have sex with men (MSM) are lacking. In addition, it is difficult to analyze the effect of STI on HIV acquisition given that sexual risk behaviors confound the relationship between bacterial STIs and incident HIV. The I...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/AID.2015.0013
更新日期:2015-06-01 00:00:00
abstract::We examined the sera from 14 HIV-1 seroconverters for the presence of autoantibodies against CD4. Anti-CD4 antibodies were detected in the serum of 11 of 13 HIV-1-infected persons at the time of HIV-1 seroconversion. In 6 of 14 persons from whom a serum was obtained prior to HIV-1 seroconversion, anti-CD4 antibodies w...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章,多中心研究
doi:10.1089/aid.1992.8.1919
更新日期:1992-11-01 00:00:00
abstract::The HIV-1 subtype distribution in 83 HIV-1-seropositive individuals living in Greece was investigated by using the heteroduplex mobility assay (HMA), DNA sequencing, and phylogenetic analysis. The results revealed that partial HIV-1 gp120 sequences from 71 (86%) patients were subtype B, 5 (6%) were subtype A, 4 were s...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章,多中心研究
doi:10.1089/aid.1998.14.685
更新日期:1998-05-20 00:00:00
abstract::The cells responsible for the second phase decay of HIV-1 viremia following the initiation of antiretroviral therapy have yet to be identified. A dynamic model that considers where drugs act in the virus life cycle places constraints on candidate cell types. In this regard, the rapid drop in viremia in patients starti...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/AID.2010.0199
更新日期:2011-07-01 00:00:00
abstract::Antibodies (Abs) against HLA and other cell surface molecules, which HIV-1 acquires during the budding process at the host cell surface, neutralize HIV-1 in vitro. Macaques were protected against infection by SIV grown in human cells after xenoimmunization with human MHC molecules. Besides the immune responses arising...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/088922299311051
更新日期:1999-04-10 00:00:00
abstract::Adult T cell leukemia/lymphoma has only rarely been reported in Europe. We aimed to determine the clinical characteristics and outcome of adult T cell leukemia/lymphoma patients in a nonendemic country. Cases of adult T cell leukemia/lymphoma managed at Hospital Universitari Vall d'Hebron, Barcelona, Spain were review...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/AID.2012.0185
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journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1991.7.453
更新日期:1991-05-01 00:00:00
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journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1988.4.51
更新日期:1988-02-01 00:00:00
abstract::HIV subtype characterization is an important tool to monitor the genetic variation of the HIV epidemic. This study investigated the current HIV subtype distribution and recombination among the northern Thai population. An in-house genotypic assay of HIV protease and reverse transcriptase genes was performed on 420 pla...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/AID.2010.0257
更新日期:2011-11-01 00:00:00
abstract::Perinatal antiretroviral (ARV) exposure has been related to hyperlactatemia and lactic acidosis in infants born to HIV-infected mothers. Our objective was to determine the incidence of these conditions during the first year of life in uninfected infants born to HIV-infected mothers and compare the data with infants bo...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/AID.2011.0198
更新日期:2012-08-01 00:00:00
abstract::In this study, the relationship between biological phenotypes, coreceptor usages, and sequence patterns of V1V2 or V3 regions on HIV-1 envelope gp 120 was carefully analyzed based on the existing isolates in the Los Alamos National Laboratory sequence database. Obviously, SI/NSI phenotypes were closely linked to the c...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2005.21.234
更新日期:2005-03-01 00:00:00
abstract::HIV-1-infected patients develop a generalized vasculopathy that is clinically most evident as Kaposi's sarcoma (KS), a multifocally appearing endothelial cell-derived tumor. Fibroblast growth factor 2 (FGF-2) is a potent autocrine and paracrine mitogen of endothelial cells and has been implicated in the cell prolifera...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/088922201300343717
更新日期:2001-07-20 00:00:00
abstract::Transmission of HIV-1 and drug resistance continue to occur at a considerable level in Italy, influenced mainly by changes in modality of infection. However, the long period of infectivity makes difficult the interpretation of epidemiological networks, based on epidemiological data only. We studied 510 naive HIV-1-inf...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2011.0245
更新日期:2012-08-01 00:00:00
abstract::A new syncytia-inducing human immunodeficiency virus type 1 (HIV-1) strain designated PokA79 was first isolated from a peripheral blood mononuclear cells (PBMC) pool from 24 HIV-1-infected patients from Russia and adapted to growth in MT2, MT4, and U937 cell cultures. The full-length genome of this isolate was amplifi...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/AID.2011.0302
更新日期:2012-09-01 00:00:00
abstract::HIV patients beginning antiretroviral therapy (ART) with advanced immunodeficiency often retain low CD4+ T cell counts despite virological control. We examined proliferative responses and upregulation of costimulatory molecules, following anti-CD3 stimulation, in HIV patients with persistent CD4+ T cell deficiency on ...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/AID.2015.0327
更新日期:2017-02-01 00:00:00
abstract::We describe four full-length genomic sequences of HIV-1 subtype B isolates from Russia. These full-length HIV-1 genomes were amplified by nested polymerase chain reaction and sequenced. The sequences obtained were subjected to neighbor-joining phylogenetic analysis using a Kimura two-parameter model and to detailed se...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2006.22.1192
更新日期:2006-11-01 00:00:00