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 predictive value of virological response to lopinavir (LPV)/ritonavir (r) was assessed in 126 HIV-infected patients who failed antiretroviral therapy and had begun a rescue intervention based on LPV/r. At 3 months, subjects with < or =6 protease (PRO) resistance mutations showed a higher rate of virological respon...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/088922204322996509
更新日期:2004-03-01 00:00:00
abstract::This study seeks to analyze nearly full-length viral genomes for distinct genetic characteristics that are unique to local or regional strains and to identify regions that have high variability or are highly conserved. Nearly full length sequences of seven HIV-1 samples were obtained to ascertain the circulating subty...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2010.0106
更新日期:2011-01-01 00:00:00
abstract::Preexposure prophylaxis (PrEP) with antiretroviral drugs constitutes a promising strategy for HIV prevention. Potent PrEP regimens with reverse transcriptase inhibitors can prevent detectable SHIV infection in a repeated low-dose macaque model that resembles human transmission, supporting plans to quickly move this ap...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2007.0222
更新日期:2008-04-01 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::Replacing the Pseudomonas exotoxin A (PE) cell binding domain with the human immunodeficiency virus (HIV) gp120 binding domain from CD4 yields a hybrid toxin (CD4-PE) with potential therapeutic use in treating acquired immunodeficiency syndrome (AIDS). To find the most therapeutically potent combination of CD4 and PE ...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1991.7.393
更新日期:1991-04-01 00:00:00
abstract::HIV-1 disease is associated with many infectious and neoplastic complications. This is particularly true of the genitourinary tract, where high rates of renal disease, neoplasms, voiding and erectile dysfunction, hematuria, opportunistic genitourinary infections, and epididymo-orchitis are found in HIV-1-infected indi...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:
更新日期:1998-04-01 00:00:00
abstract::Elderly people living with HIV are increasing. At present in the United States, nearly half of newly diagnosed HIV-infected people are aged >50 years. Diagnosis and treatment of HIV-infected elderly patients tends to be delayed by several health care factors as several life-threatening diseases are common in elderly p...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/AID.2019.0098
更新日期:2020-06-01 00:00:00
abstract::We have previously used immunotoxins to select for HIV-1 variant cells that transcribe HIV at extremely low levels and fail to produce HIV proteins. Further observation of one of these variants (E9) demonstrated spontaneous in vitro activation of HIV production. The mechanism of activation is different from that of U1...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章,评审
doi:10.1089/088922299310052
更新日期:1999-10-10 00:00:00
abstract::The Tax protein encoded by HTLV-1 plays a key role in the development of ATL in infected individuals. Our previous studies showed that tax transgenic mice develop disease that is almost identical to human ATL, with widespread organ invasion by lymphomatous cells and the development of leukemia. The same pathology deve...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2009.0212
更新日期:2010-05-01 00:00:00
abstract::Reports indicate that myeloid and plasmacytoid dendritic cells (mDCs and pDCs), which are key effector cells in host innate immune responses, can be infected with HIV-1 and are reduced in number and function during the chronic phase of HIV disease. Furthermore, it was recently demonstrated that a sustained loss of mDC...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2009.0053
更新日期:2009-12-01 00:00:00
abstract::A sequence of four amino acid residues amino-terminal to the only intramolecular disulphide bond of the human immunodeficiency virus type 1 (HIV-1) transmembrane protein gp41 is recognized by an anti-idiotypic antibody (9G5A) raised against another monoclonal antibody (M38), which recognizes the C5 region of gp120. 9G...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1993.9.33
更新日期:1993-01-01 00:00:00
abstract::As antiretroviral therapy continues to scale-up in developing countries, there is concern that high levels of HIV drug resistance to antiretroviral drugs will occur. Here we describe rates of emergence of HIV-1 drug resistance and factors associated with their occurrence among adults who received antiretroviral therap...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2008.0273
更新日期:2009-05-01 00:00:00
abstract::We have characterized human foamy virus (HFV) proviral DNA and determined HFV expression in a persistent infection model, the Dami megakaryocytic cell line. Molecular studies were performed on parental persistently infected cells (Dami-P), as well as on derived clones (Dami-Cl). We report that in these nonlytic and no...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1995.11.829
更新日期:1995-07-01 00:00:00
abstract::GLQ223 is a formulated version of tricosanthin, a single-chain ribosome-inactivating protein that was shown in earlier studies to inhibit human immunodeficiency virus (HIV) replication in T-lymphoblastoid cells and to decrease HIV p24 levels in HIV-infected monocyte-derived macrophages as measured by flow cytometry. T...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1990.6.1039
更新日期:1990-08-01 00:00:00
abstract::A potential strategy to combat the worldwide AIDS epidemic is to develop a vaginal microbicide that prevents the sexual transmission of HIV-1. One approach for preventing vaginal HIV transmission is to block the viral coreceptor CCR5 with naturally occurring chemokine ligands. In this study, we used a cynomolgus macaq...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2006.0076
更新日期:2007-01-01 00:00:00
abstract::The chemokine polymorphisms CXCR6-3E/K, In1.1T/C, H7 haplotype, CX(3)CR1-V249I, and CX(3)CR1-T280M have been shown to affect the course of HIV infection. We studied their influence on immunologic and virologic response to HAART in a group of 143 HIV-1 patients. We performed Kaplan-Meier analysis using the following en...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2006.0248
更新日期:2007-08-01 00:00:00
abstract::The relative importance of routes of transmission of human T cell lymphotropic virus type 1 (HTLV-1) in Guinea-Bissau is largely unknown; vertical transmission is thought to be important, but there are very few existing data. We aimed to examine factors associated with transmission in mothers and children in Guinea-Bi...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/AID.2011.0219
更新日期:2012-06-01 00:00:00
abstract::Nucleoside analog reverse transcriptase inhibitors (NRTIs) constitute the most commonly used drugs in antiretroviral therapy. NRTIs differ with respect to their host cell toxicity. We compared the in vitro effect of zidovudine (AZT; 2 μg/ml), lamivudine (3TC; 5 μg/ml), stavudine (d4T; 1 μg/ml), and tenofovir (TFV; 1 μ...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2010.0067
更新日期:2011-01-01 00:00:00
abstract::Many aspects of HIV-1 pathogenesis are affected by Nef protein activity, and efforts have been made to study variation in the nef gene and how that variation relates to disease outcome. We studied the genetic diversity of the nef gene in distinct clones obtained from the same patient (intrahost) and in sequences obtai...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2009.0061
更新日期:2009-11-01 00:00:00
abstract::India has experienced multiple introductions of diverse HIV-1 subtypes A, B, C, and E, along with subtype B of HIV-2 between the 1980s and early 1990s. In this study, we have carried out a molecular investigation of 21 heterosexually and vertically acquired HIV-infected individuals from the New Bombay area, who tested...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/088922201300119743
更新日期:2001-05-01 00:00:00
abstract::Although the breadth of the human immunodeficiency virus type 1 (HIV-1)-specific cellular immune response and its impact on the control of viral replication have already been addressed, reported data have proven controversial. We hypothesize that the nature of targeted epitopes, rather than the simple breadth or magni...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/AID.2016.0168
更新日期:2017-08-01 00:00:00
abstract::Thymulin is a thymic peptide important for the maturation and differentiation of immature thymocytes, which have been found to be depressed in patients with low-level CD4(+) cell recovery despite viral control. Substance use is associated with faster progression of HIV disease, which has been ascribed to poor adherenc...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/AID.2010.0086
更新日期:2011-08-01 00:00:00
abstract::To investigate how human immunodeficiency virus type 1 (HIV-1) escapes from antibodies directed against the neutralization domain in the third variable region (V3) of gp120, we examined precisely which amino acid contributed to antibody binding. From six HIV-1-infected individuals, sequential sera were tested for anti...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1995.11.1153
更新日期:1995-10-01 00:00:00
abstract::In recent years, increasing numbers of patients infected with HIV-1 non-B subtypes have been treated with modern antiretroviral regimens. Therefore, a better knowledge of HIV drug resistance in non-B strains is crucial. Thus, we compared the mutational pathways involved in drug resistance among the most common non-B s...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/AID.2011.0142
更新日期:2012-10-01 00:00:00
abstract::The aim of this study was to evaluate the immunological responses induced by DNA plasmids containing HIV regulatory genes administered in combination in HIV-1-infected patients with pretreatment with highly active antiretroviral treatment (HAART). The study is a double-blind, randomized, and placebo-controlled study, ...
journal_title:AIDS research and human retroviruses
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1089/0889222041725190
更新日期:2004-08-01 00:00:00
abstract::The long-term efficacy of once-daily (qd) fosamprenavir (FPV) 1400 mg boosted by ritonavir 100 mg (FPV/r100) has not been evaluated previously. A 96-week open-label, randomized, multicenter study compared the efficacy/safety of FPV/r100 with FPV 1400 mg boosted by ritonavir 200 mg qd (FPV/r200), plus abacavir/lamivudi...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1089/aid.2008.0231
更新日期:2009-04-01 00:00:00
abstract::We have determined that polymeric IgA in saliva of HIV-1-uninfected individuals binds in varying degrees to components of culture supernatants containing HIV-1 recombinant proteins when ELISA is used for the determination. This finding did not extend to salivary IgG antibodies. Further, such problems were not encounte...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/088922200309016
更新日期:2000-04-10 00:00:00
abstract::Vaginal anti-HIV antibody responses may be beneficial, and possibly required, for vaccine-induced protection against HIV infection acquired through receptive vaginal intercourse. We have previously determined that intranasal immunization with a hybrid HIV peptide and cholera toxin induced vaginal anti-HIV IgA response...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1997.13.945
更新日期:1997-07-20 00:00:00
abstract::Human immunodeficiency virus (HIV) infection represents a major global health problem, with HIV now recognized as the fourth leading cause of death on a worldwide basis. One approach to developing effective anti- HIV interventions is to identify and understand the molecular mechanisms by which natural genetic variatio...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2006.22.925
更新日期:2006-10-01 00:00:00
abstract::HIV-1 and HTLV-1 infect CD4(+) T lymphocyte but little is known about the impact of coinfection on patient's immune response. In this study we have evaluated the spontaneous production of interleukin (IL)-2, IL-4, IL-6, and IL-10 and interferon (IFN)-γ by unstimulated peripheral blood mononuclear cell (PBMC) cultures ...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/AID.2011.0192
更新日期:2012-08-01 00:00:00