Article

Oral pre-exposure prophylaxis for HIV prevention

Division of HIV/AIDS Prevention, National Center for HIV, Hepatitis, STD, and Prevention, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30329, USA.
Trends in Pharmacological Sciences (Impact Factor: 9.99). 12/2009; 31(2):74-81. DOI: 10.1016/j.tips.2009.10.009
Source: PubMed

ABSTRACT In the absence of an effective vaccine, HIV continues to spread worldwide, emphasizing the need for new biomedical interventions to limit its transmission. Appreciation of the challenges that HIV has to face to initiate an infection mucosally has spurred interest in evaluating the use of antiretroviral drugs to prevent infection. Recent animal studies using macaques or humanized mice models of mucosal transmission of SIV or HIV have shown that daily or intermittent pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) can exploit early virus vulnerabilities and effectively prevent establishment of infection. These preclinical findings have fueled interest in evaluating the safety and efficacy of PrEP in humans. We provide an overview of the rationale behind PrEP and discuss the next steps in PrEP research, including the need to better define the ability of current drugs to reach and accumulate in mucosal tissues and protect cells that are primary targets during early HIV infection.

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    • "Prevention of HIV-1 infection to reduce the number of newly infected individuals is an international priority. Various modalities such as male circumcision (Warner et al., 2009), prophylactic HIV vaccines (Munier et al., 2011), vaginal microbicides (Kelly and Shattock, 2011) and oral pre-exposure prophylaxis (García-Lerma et al., 2010) have been explored to prevent sexual contraction of HIV. Prevention of HIV infection by using antiretroviral agents as vaginal microbicides has received more attention in recent years. "
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    ABSTRACT: The objective of this investigation was to develop a thermosensitive vaginal gel containing raltegravir+efavirenz loaded PLGA nanoparticles (RAL-EFV-NPs) for pre-exposure prophylaxis of HIV. RAL-EFV-NPs were fabricated using a modified emulsion-solvent evaporation method and characterized for size and zeta potential. The average size and surface charge of RAL-EFV-NP were 81.8±6.4nm and -23.18±7.18mV respectively. The average encapsulation efficiency of raltegravir and efavirenz was 55.5% and 98.2% respectively. Thermosensitive vaginal gel containing RAL-EFV-NPs was successfully prepared using a combination of Pluronic F127 (20% w/v) and Pluronic F68 (1% w/v). Incorporation RAL-EFV-NPs in the gel did not result in nanoparticle aggregation and RAL-EFV-NPs containing gel showed thermogelation at 32.5°C. The RAL-EFV-NPs were evaluated for inhibition of HIV-1(NL4-3) using TZM-bl indicator cells. The EC(90) of RAL-EFV-NPs was lower than raltegravir+efavirenz (RAL-EFV) solution but did not reach significance. Compared to control HeLa cells without any treatment, RAL-EFV-NPs or blank gel were not cytotoxic for 14days in vitro. The intracellular levels of efavirenz in RAL-EFV-NPs treated HeLa cells were above the EC(90) for 14days whereas raltegravir intracellular concentrations were eliminated within 6days. Transwell experiments of NPs-in-gel demonstrated rapid transfer of fluorescent nanoparticles from the gel and uptake in HeLa cells within 30min. These data demonstrate the potential of antiretroviral NP-embedded vagina gels for long-term vaginal pre-exposure prophylaxis of heterosexual HIV-1 transmission.
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    • "The concept of targeted systemic PrEP involves the continuous treatment of HIV-1-negative individuals at high risk for acquiring HIV-1 with antiretroviral drugs in an effort to prevent HIV-1 transmission (Garcia-Lerma et al., 2010). However, there are major concerns regarding the potential side effects of the drugs used because systemic PrEP entails the administration of antiretroviral drugs to large numbers of otherwise healthy individuals (Derdelinckx et al., 2006). "
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