Intermittent Prophylaxis with Oral Truvada Protects Macaques from Rectal SHIV Infection

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.
Science translational medicine (Impact Factor: 15.84). 01/2010; 2(14):14ra4. DOI: 10.1126/scitranslmed.3000391
Source: PubMed


HIV continues to spread globally, mainly through sexual contact. Despite advances in treatment and care, preventing transmission with vaccines or microbicides has proven difficult. A promising strategy to avoid transmission is prophylactic treatment with antiretroviral drugs before exposure to HIV. Clinical trials evaluating the efficacy of daily treatment with the reverse transcriptase inhibitors tenofovir disoproxil fumarate (TDF) or Truvada (TDF plus emtricitabine) are under way. We hypothesized that intermittent prophylactic treatment with long-acting antiviral drugs would be as effective as daily dosing in blocking the earliest stages of viral replication and preventing mucosal transmission. We tested this hypothesis by intermittently giving prophylactic Truvada to macaque monkeys and then exposing them rectally to simian-human immunodeficiency virus (SHIV) once a week for 14 weeks. A simple regimen with an oral dose of Truvada given 1, 3, or 7 days before exposure followed by a second dose 2 hours after exposure was as protective as daily drug administration, possibly because of the long intracellular persistence of the drugs. In addition, a two-dose regimen initiated 2 hours before or after virus exposure was effective, and full protection was obtained by doubling the Truvada concentration in both doses. We saw no protection if the first dose was delayed until 24 hours after exposure, underscoring the importance of blocking initial replication in the mucosa. Our results show that intermittent prophylactic treatment with an antiviral drug can be highly effective in preventing SHIV infection, with a wide window of protection. They strengthen the possibility of developing feasible, cost-effective strategies to prevent HIV transmission in humans.

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Available from: Ae S Youngpairoj
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    • "As more acceptable PrEP regimens are being developed to improve adherence, there has been great interest in intermittent PrEP. Indeed, in animal models, oral intermittent PrEP, given at the time of virus inoculation, whether by vaginal or rectal challenge, provided an efficacy similar to that provided by use of daily PrEP [29]. This strategy of coitus-dependent PrEP is currently being assessed in two PrEP trials in MSM, under the assumption that the convenience of the regimen could increase PrEP adherence and therefore PrEP efficacy [30,31]. "
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    • "SHIV162P3 is a chimeric virus that contains the tat, rev, and env coding regions of HIV-1SF162 in a SIVmac239 background (National Institutes of Health AIDS Research and Reference Reagent Program [26]). All animals became infected during repeated weekly non-traumatic exposures to a low dose (10 TCID50) of SHIV162P3 as previously described [7,8]. Macaques AG80 and AG46 received daily PrEP with human-equivalent doses of FTC (20 mg/kg) and became infected after 5 and 10 rectal exposures, respectively. "
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    • "Tsai [8] later demonstrated the improved efficacy of PMPA (tenofovir) over zidovudine in protecting adult macaques against intravenous SIV challenge. More recent studies have demonstrated the efficacy of tenofovir or Truvada® in preventing infections when animals are challenged rectally with SIV [9]. "
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