Single-Tablet Emtricitabine-Rilpivirine-Tenofovir as HIV Postexposure Prophylaxis in Men Who Have Sex With Men

Foster, Rosalind; McAllister, John; Read, Timothy Richard; Pierce, Anna; Richardson, Robyn; McNulty, Anna; Carr, Andrew

doi:10.1093/cid/civ511

Cited by 39 publications

(25 citation statements)

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“…One of the studies showed that in MSM, a single tablet of FTC‐RPV‐TDF effectively protected the participants from HIV. It was well tolerated with high adherence to the drug by the participants . RPV on macaques infected with SIV containing HIV‐1 reverse transcriptase (RT) helped to decrease plasma viremia, and the effect lasted for about 15 weeks.…”

Section: Non‐nucleoside Reverse Transcriptase Inhibitormentioning

confidence: 99%

Antiretroviral agents in pre-exposure prophylaxis: emerging and advanced trends in HIV prevention

Yap

Xin

Tan

et al. 2019

Journal of Pharmacy and Pharmacology

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Objectives Antiretroviral agents (ARVs) have been the most promising line of therapy in the management of human immunodeficiency virus (HIV) infections. Some of these ARVs are used in the pre-exposure prophylaxis (PrEP) to suppress the transmission of HIV. Prophylaxis is primarily used in uninfected people, before exposure, to effectively prevent HIV infection. Several studies have shown that ART PrEP prevents HIV acquisition from sexual, blood and mother-to-child transmissions. However, there are also several challenges and limitations to PrEP. This review focuses on the current antiretroviral therapies used in PrEP. Key findings Among ARVs, the most common drugs employed from the class of entry inhibitors are maraviroc (MVC), which is a CCR5 receptor antagonist. Other entry inhibitors like emtricitabine (FTC) and tenofovir (TFV) are also used. Rilpivirine (RPV) and dapivirine (DPV) are the most common drugs employed from the Non-nucleoside reverse transcriptase inhibitor (NNRTIs) class, whereas, tenofovir disoproxil fumarate (TDF) is primarily used in the Nucleoside Reverse Transcriptase Inhibitor (NRTIs) class. Cabotegravir (CAB) is an analog of dolutegravir, and it is an integrase inhibitor. Some of these drugs are also used in combination with other drugs from the same class. Summary Some of the most common pre-exposure prophylactic strategies employed currently are the use of inhibitors, namely entry inhibitors, non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors, integrase and protease inhibitors. In addition, we have also discussed on the adverse effects caused by ART in PrEP, pharmacoeconomics factors and the use of antiretroviral prophylaxis in serodiscordant couples.HIV and pre-exposure prophylaxis Pui Khee Yap et al.

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Section: Non‐nucleoside Reverse Transcriptase Inhibitormentioning

confidence: 99%

Antiretroviral agents in pre-exposure prophylaxis: emerging and advanced trends in HIV prevention

Yap

Xin

Tan

et al. 2019

Journal of Pharmacy and Pharmacology

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“…The nonnucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine (RPV) is FDA approved as a component of combination antiretroviral therapy (ART) that includes TFV disoproxil fumarate and FTC in a once-daily oral pill. RPV in combination with other antiretroviral drugs has been evaluated for efficacy as ART (7)(8)(9) and postexposure prophylaxis (10). RPV also has been developed in a nanoparticle long-acting formulation (RPV LA) to improve adherence (11,12).…”

mentioning

confidence: 99%

Long-Acting Rilpivirine (RPV) Preexposure Prophylaxis Does Not Inhibit Vaginal Transmission of RPV-Resistant HIV-1 or Select for High-Frequency Drug Resistance in Humanized Mice

Melody

Roy

Kline

et al. 2020

J Virol

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As a long-acting formulation of the nonnucleoside reverse transcriptase inhibitor rilpivirine (RPV LA) has been proposed for use as preexposure prophylaxis (PrEP) and the prevalence of transmitted RPV-resistant viruses can be relatively high, we evaluated the efficacy of RPV LA to inhibit vaginal transmission of RPV-resistant HIV-1 in humanized mice. Vaginal challenges of wild-type (WT), Y181C, and Y181V HIV-1 were performed in mice left untreated or after RPV PrEP. Plasma viremia was measured for 7 to 10 weeks, and single-genome sequencing was performed on plasma HIV-1 RNA in mice infected during PrEP. RPV LA significantly prevented vaginal transmission of WT HIV-1 and Y181C HIV-1, which is 3-fold resistant to RPV. However, it did not prevent transmission of Y181V HIV-1, which has 30-fold RPV resistance in the viruses used for this study. RPV LA did delay WT HIV-1 dissemination in infected animals until genital and plasma RPV concentrations waned. Animals that became infected despite RPV LA PrEP did not acquire new RPV-resistant mutations above frequencies in untreated mice or untreated people living with HIV-1, and the mutations detected conferred low-level resistance. These data suggest that high, sustained concentrations of RPV were required to inhibit vaginal transmission of HIV-1 with little or no resistance to RPV but could not inhibit virus with high resistance. HIV-1 did not develop high-level or high-frequency RPV resistance in the majority of mice infected after RPV LA treatment. However, the impact of low-frequency RPV resistance on virologic outcome during subsequent antiretroviral therapy still is unclear. IMPORTANCE The antiretroviral drug rilpivirine was developed into a long-acting formulation (RPV LA) to improve adherence for preexposure prophylaxis (PrEP) to prevent HIV-1 transmission. A concern is that RPV LA will not inhibit transmission of drug-resistant HIV-1 and may select for drug-resistant virus. In female humanized mice, we found that RPV LA inhibited vaginal transmission of WT or 3-fold RPV-resistant HIV-1 but not virus with 30-fold RPV resistance. In animals that became infected despite RPV LA PrEP, WT HIV-1 dissemination was delayed until genital and plasma RPV concentrations waned. RPV resistance was detected at similar low frequencies in untreated and PrEP-treated mice that became infected. These results indicate the importance of maintaining RPV at a sustained threshold after virus exposure to prevent dissemination of HIV-1 after vaginal infection and low-frequency resistance mutations conferred low-level resistance, suggesting that RPV resistance is difficult to develop after HIV-1 infection during RPV LA PrEP.

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“…If started within 72 hours of exposure and taken for 28 days with good adherence, PEP significantly reduces the likelihood of the person becoming HIV‐positive because it can stop HIV from establishing itself in a person's immune cells even after the virus has entered a person's body . Although PEP is not 100% effective, high rates of success have been reported (e.g. 81% among patients using older‐style treatments and up to 100% among patients using newer treatments ).…”

Section: Discussionmentioning

confidence: 99%

Expert consensus statement on the science of HIV in the context of criminal law

et al. 2018

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IntroductionGlobally, prosecutions for non‐disclosure, exposure or transmission of HIV frequently relate to sexual activity, biting, or spitting. This includes instances in which no harm was intended, HIV transmission did not occur, and HIV transmission was extremely unlikely or not possible. This suggests prosecutions are not always guided by the best available scientific and medical evidence.DiscussionTwenty scientists from regions across the world developed this Expert Consensus Statement to address the use of HIV science by the criminal justice system. A detailed analysis of the best available scientific and medical research data on HIV transmission, treatment effectiveness and forensic phylogenetic evidence was performed and described so it may be better understood in criminal law contexts. Description of the possibility of HIV transmission was limited to acts most often at issue in criminal cases. The possibility of HIV transmission during a single, specific act was positioned along a continuum of risk, noting that the possibility of HIV transmission varies according to a range of intersecting factors including viral load, condom use, and other risk reduction practices. Current evidence suggests the possibility of HIV transmission during a single episode of sex, biting or spitting ranges from no possibility to low possibility. Further research considered the positive health impact of modern antiretroviral therapies that have improved the life expectancy of most people living with HIV to a point similar to their HIV‐negative counterparts, transforming HIV infection into a chronic, manageable health condition. Lastly, consideration of the use of scientific evidence in court found that phylogenetic analysis alone cannot prove beyond reasonable doubt that one person infected another although it can be used to exonerate a defendant.ConclusionsThe application of up‐to‐date scientific evidence in criminal cases has the potential to limit unjust prosecutions and convictions. The authors recommend that caution be exercised when considering prosecution, and encourage governments and those working in legal and judicial systems to pay close attention to the significant advances in HIV science that have occurred over the last three decades to ensure current scientific knowledge informs application of the law in cases related to HIV.

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Single-Tablet Emtricitabine-Rilpivirine-Tenofovir as HIV Postexposure Prophylaxis in Men Who Have Sex With Men

Abstract: NCT01715636.

Cited by 39 publications

References 10 publications

Antiretroviral agents in pre-exposure prophylaxis: emerging and advanced trends in HIV prevention

Antiretroviral agents in pre-exposure prophylaxis: emerging and advanced trends in HIV prevention

Long-Acting Rilpivirine (RPV) Preexposure Prophylaxis Does Not Inhibit Vaginal Transmission of RPV-Resistant HIV-1 or Select for High-Frequency Drug Resistance in Humanized Mice

Expert consensus statement on the science of HIV in the context of criminal law

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