Proof of principle: antiretroviral drugs can prevent sexual transmission of HIV-1

2011 ◽  
Vol 6 (5) ◽  
pp. 549-551
Author(s):  
Mark A Wainberg ◽  
Hugh J Field
Keyword(s):  
Sexual Transmission ◽  
Antiretroviral Drugs ◽  
Sexual Transmission Of Hiv ◽  
Hiv 1 ◽  
Proof Of Principle

scholarly journals ADS-J1 Inhibits Semen-Derived Amyloid Fibril Formation and Blocks Fibril-Mediated Enhancement of HIV-1 Infection

2015 ◽  
Vol 59 (9) ◽  
pp. 5123-5134 ◽  
Author(s):  
Tianrong Xun ◽  
Wenjuan Li ◽  
Jinquan Chen ◽  
Fei Yu ◽  
Wei Xu ◽  
...  
Keyword(s):  
Viral Infection ◽  
Amyloid Fibrils ◽  
Synergistic Effects ◽  
Sexual Transmission ◽  
Prostatic Acid Phosphatase ◽  
Fibril Formation ◽  
Antiretroviral Drugs ◽  
Target Cells ◽  
Additional Function ◽  
Hiv 1

ABSTRACTSemen-derived enhancer of viral infection (SEVI) is composed of amyloid fibrils that can greatly enhance HIV-1 infectivity. By its cationic property, SEVI promotes viral sexual transmission by facilitating the attachment and internalization of HIV-1 to target cells. Therefore, semen-derived amyloid fibrils are potential targets for microbicide design. ADS-J1 is an anionic HIV-1 entry inhibitor. In this study, we explored an additional function of ADS-J1: inhibition of SEVI fibril formation and blockage of SEVI-mediated enhancement of viral infection. We found that ADS-J1 bound to an amyloidogenic peptide fragment (PAP248–286, comprising amino acids 248 to 286 of the enzyme prostatic acid phosphatase), thereby inhibiting peptide assembly into amyloid fibrils. In addition, ADS-J1 binds to mature amyloid fibrils and antagonizes fibril-mediated enhancement of viral infection. Unlike cellulose sulfate, a polyanion that failed in clinical trial to prevent HIV-1 sexual transmission, ADS-J1 shows no ability to facilitate fibril formation. More importantly, the combination of ADS-J1 with several antiretroviral drugs exhibited synergistic effects against HIV-1 infection in semen, with little cytotoxicity to vaginal epithelial cells. Our results suggest that ADS-J1 or a derivative may be incorporated into a combination microbicide for prevention of the sexual transmission of HIV-1.

Cost-effectiveness of voluntary HIV-1 counselling and testing in reducing sexual transmission of HIV-1 in Kenya and Tanzania

The Lancet ◽  
2000 ◽  
Vol 356 (9224) ◽  
pp. 113-121 ◽  
Author(s):  
Michael Sweat ◽  
Steven Gregorich ◽  
Gloria Sangiwa ◽  
Colin Furlonge ◽  
Donald Balmer ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Sexual Transmission ◽  
Sexual Transmission Of Hiv ◽  
Hiv 1

Factors Facilitating the Sexual Transmission of HIV-1

1997 ◽  
Vol 11 (3) ◽  
pp. 167-177 ◽  
Author(s):  
ANN K. SULLIVAN ◽  
MARK C. ATKINS ◽  
FIONA BOAG
Keyword(s):  
Sexual Transmission ◽  
Sexual Transmission Of Hiv ◽  
Hiv 1

scholarly journals Factors Important to the Prioritization and Development of Successful Topical Microbicides for HIV-1

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Karen W. Buckheit ◽  
Robert W. Buckheit
Keyword(s):  
Clinical Trials ◽  
Ex Vivo ◽  
Sexual Transmission ◽  
Virus Transmission ◽  
Preclinical Development ◽  
Sexual Transmission Of Hiv ◽  
The Right ◽  
Hiv 1

Significant advancements in topical microbicide development have occurred since the prevention strategy was first described as a means to inhibit the sexual transmission of HIV-1. The lack of clinical efficacy of the first generation microbicide products has focused development attention on specific antiretroviral agents, and these agents have proven partially successful in human clinical trials. With greater understanding of vaginal and rectal virus infection, replication, and dissemination, better microbicide products and delivery strategies should result in products with enhanced potency. However, a variety of development gaps exist which relate to product dosing, formulation and delivery, and pharmacokinetics and pharmacodynamics which must be better understood in order to prioritize microbicide products for clinical development. In vitro, ex vivo, and in vivo models must be optimized with regard to these development gaps in order to put the right product at the right place, at the right time, and at the right concentration for effective inhibition of virus transmission. As the microbicide field continues to evolve, we must harness the knowledge gained from unsuccessful and successful clinical trials and development programs to continuously enhance our preclinical development algorithms.

Herpes simplex virus and HIV: genital infection synergy and novel approaches to dual prevention

2012 ◽  
Vol 23 (9) ◽  
pp. 613-619 ◽  
Author(s):  
A R Thurman ◽  
G F Doncel
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Sexual Transmission ◽  
Topical Administration ◽  
Efficient Data ◽  
Sexual Transmission Of Hiv ◽  
Simplex Virus ◽  
Exposure Prophylaxis ◽  
Hiv 1

Sexual transmission of HIV-1, in the absence of co-factors, is poorly efficient. Data support that herpes simplex virus type-2 (HSV-2) may increase a woman's susceptibility to HIV-1. Potential mechanisms by which HSV-2 serves as an HIV-1 enhancing co-factor include (1) initiation of a clinical or subclinical mucosal inflammatory response, (2) alteration of innate mucosal immunity and (3) weakening or breaching the protective genital epithelia. No clinical trial has examined prevention of primary HSV-2 infection to eliminate the major morbidities of this recurrent disease and as a strategy to reduce HIV-1 transmission. Topical administration of potent antivirals can achieve local concentrations that are orders of magnitude higher than those obtained with oral administration. This paper reviews major advances in oral and topical pre-exposure prophylaxis of HIV-1 and HSV-2 and, based on these data, hypothesizes that simultaneous prevention of sexual acquisition of HSV-2 and HIV-1 via topical antiretroviral agents will have a synergistic impact on both epidemics.

scholarly journals A role for cell migration in the sexual transmission of HIV-1?

1997 ◽  
Vol 7 (7) ◽  
pp. 534-537 ◽  
Author(s):  
Vanaja R. Zacharopoulos ◽  
Maria-Elisa Perotti ◽  
David M. Phillips
Keyword(s):  
Cell Migration ◽  
Sexual Transmission ◽  
Sexual Transmission Of Hiv ◽  
Hiv 1
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