Determining Seminal Plasma Human Immunodeficiency Virus Type 1 Load in the Context of Efficient Highly Active Antiretroviral Therapy

Pasquier, Christophe; Sauné, Karine; Raymond, Stéphanie; Moinard, Nathalie; Daudin, Myriam; Bujan, Louis; Izopet, Jacques

doi:10.1128/jcm.02131-08

Cited by 23 publications

(16 citation statements)

References 32 publications

(32 reference statements)

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“…Fisher's exact test was performed to determine statistical significance. greater than that present in human semen [33][34][35][36] and thus represents a stringent test of microbicide efficacy. That the protection offered by MZC gel compared to CG (with only 3/6 infections) was statistically significant is a testament to the strength of the microbicide protection.…”

Section: Discussionmentioning

confidence: 99%

A Combination Microbicide Gel Protects Macaques Against Vaginal Simian Human Immunodeficiency Virus-Reverse Transcriptase Infection, But Only Partially Reduces Herpes Simplex Virus-2 Infection After a Single High-Dose Cochallenge

Hsu

Aravantinou

Menon

et al. 2014

AIDS Research and Human Retroviruses

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Herpes simplex virus-2 (HSV-2) infection increases HIV susceptibility. We previously established a rhesus macaque model of vaginal HSV-2 preexposure followed by cochallenge with HSV-2 and simian/human immunodeficiency virus-reverse transcriptase (SHIV-RT). Using this model, we showed that a gel containing the nonnucleoside reverse transcriptase inhibitor (NNRTI) MIV-150 in carrageenan (CG) reduced SHIV-RT infection. To evaluate the efficacy of new generation microbicides against both viruses, we first established dual infection after single vaginal cochallenge with SHIV-RT and HSV-2 in HSV-2-naive macaques. All animals (6/6) became HSV-2 infected, with 4/6 coinfected with SHIV-RT. In a control group cochallenged with SHIV-RT and UV-inactivated HSV-2, 2/4 became SHIV-RT infected, and none had detectable HSV-2. Low-level HSV-2-specific antibody and T cell responses were detected in some HSV-2-infected animals. To test a CG gel containing MIV-150 and zinc acetate (MZC), which provided naive animals full protection from SHIV-RT for at least 8 h, MZC (vs. CG) was applied daily for 14 days followed by cochallenge 8 h later. MZC prevented SHIV-RT infection (0/9 infected, p=0.04 vs. 3/6 in CG controls), but only reduced HSV-2 infection by 20% (6/9 infected vs. 5/6 in CG, p=0.6). In HSV-2-infected animals, none of the gel-treated animals seroconverted, and only the CG controls had measurable HSV-2-specific T cell responses. This study shows the promise of MZC to prevent immunodeficiency virus infection (even in the presence of HSV-2) and reduce HSV-2 infection after exposure to a high-dose inoculum. Additionally, it demonstrates the potential of a macaque coinfection model to evaluate broad-spectrum microbicides.

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Section: Discussionmentioning

confidence: 99%

A Combination Microbicide Gel Protects Macaques Against Vaginal Simian Human Immunodeficiency Virus-Reverse Transcriptase Infection, But Only Partially Reduces Herpes Simplex Virus-2 Infection After a Single High-Dose Cochallenge

Hsu

Aravantinou

Menon

et al. 2014

AIDS Research and Human Retroviruses

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show abstract

“…These inocula contained Ͼ1.6 ϫ 10 6 to 1.6 ϫ 10 7 RNA copies, which is at least 100-to 1,000-fold greater than the median virus RNA levels in human semen (5,19,20,40). Although the relevance of the single high-dose challenge model to human HIV exposure has been questioned (25,34), infecting with a high inoculum highlights the stringency of the test model, pushing the limits of the microbicide to block infection.…”

Section: Discussionmentioning

confidence: 99%

The Nonnucleoside Reverse Transcriptase Inhibitor MIV-150 in Carrageenan Gel Prevents Rectal Transmission of Simian/Human Immunodeficiency Virus Infection in Macaques

Singer

Derby

Rodríguez

et al. 2011

J Virol

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“…42,43 In addition to lowering plasma viral load to nearly undetectable levels, ART can decrease viral load in genital secretions, 44,45 although patients having a detectable semen HIV load may have no detectable virus in their blood plasma, highlighting the residual risk of HIV-1 transmission during unprotected intercourse. 46 Observational studies and recent modeling work have triggered considerable interest and concerns regarding the use of ART in HIV-infected individuals to prevent secondary transmission. 32,[47][48][49][50][51][52][53][54] In the coming years, systemic PrEP or drug-based microbicides (which in this discussion is considered a topical form of PrEP) may be proven to safely confer protection against HIV infection.…”

Section: Introductionmentioning

confidence: 99%

AIDS Vaccines and Preexposure Prophylaxis: Is Synergy Possible?

Excler

Rida²,

Priddy

et al. 2011

AIDS Research and Human Retroviruses

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While the long-term goal is to develop highly effective AIDS vaccines, first generation vaccines may be only partially effective. Other HIV prevention modalities such as preexposure prophylaxis with antiretrovirals (PrEP) may have limited efficacy as well. The combined administration of vaccine and PrEP (VAXPREP), however, may have a synergistic effect leading to an overall benefit that is greater than the sum of the individual effects. We propose two test-of-concept trial designs for an AIDS vaccine plus oral or topical ARV. In one design, evidence that PrEP reduces the risk of HIV acquisition is assumed to justify offering it to all participants. A two-arm study comparing PrEP alone to VAXPREP is proposed in which 30 to 60 incident infections are observed to assess the additional benefit of vaccination on risk of infection and setpoint viral load. The demonstrated superiority of VAXPREP does not imply vaccine alone is efficacious. Similarly, the lack of superiority does not imply vaccine alone is ineffective, as antagonism could exist between vaccine and PrEP. In the other design, PrEP is assumed not to be in general use. A 2Â2 factorial design is proposed in which high-risk individuals are randomized to one of four arms: placebo vaccine given with placebo PrEP, placebo vaccine given with PrEP, vaccine given with placebo PrEP, or VAXPREP. Between 60 and 210 infections are required to detect a benefit of vaccination with or without PrEP on risk of HIV acquisition or setpoint viral load, with fewer infections needed when synergy is present.

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Determining Seminal Plasma Human Immunodeficiency Virus Type 1 Load in the Context of Efficient Highly Active Antiretroviral Therapy

Cited by 23 publications

References 32 publications

A Combination Microbicide Gel Protects Macaques Against Vaginal Simian Human Immunodeficiency Virus-Reverse Transcriptase Infection, But Only Partially Reduces Herpes Simplex Virus-2 Infection After a Single High-Dose Cochallenge

A Combination Microbicide Gel Protects Macaques Against Vaginal Simian Human Immunodeficiency Virus-Reverse Transcriptase Infection, But Only Partially Reduces Herpes Simplex Virus-2 Infection After a Single High-Dose Cochallenge

The Nonnucleoside Reverse Transcriptase Inhibitor MIV-150 in Carrageenan Gel Prevents Rectal Transmission of Simian/Human Immunodeficiency Virus Infection in Macaques

AIDS Vaccines and Preexposure Prophylaxis: Is Synergy Possible?

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