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Background: Approximately 1.5 million HIV-positive women become pregnant annually. Without treatment, up to 45% will transmit HIV to their infants, primarily through breastfeeding. These numbers indicate the fact that HIV acquisition is a major health concern for women and children globally. They also highlight the urgent need for novel approaches to prevent HIV acquisition that are safe, effective and convenient to use by women and children in places where they are most needed.
Methods: The efficacy of oral EFdA PrEP to prevent vaginal and oral HIV infection in vivo was evaluated by exposing EFdA-treated and untreated BLT humanized mice vaginally (HIV-1JR-CSF, HIV-1CH040 and HIV-1RHPA) or orally (HIV-1JR-CSF, HIV-1CH4419 and HIV-1THRO) to three consecutive high dose HIV challenges. EFdA was administered via oral gavage (10 mg/kg) once daily for eight days and mice were challenged with HIV 3-4 h after the second, fourth and sixth EFdA doses. A power analysis was performed to determine experimental group sizes needed to achieve ~90% power.
Results: Using highly relevant transmitted-founder (T/F) viruses, we evaluated the ability of a novel and potent reverse transcriptase inhibitor, EFdA, to prevent vaginal and oral HIV transmission using a pre-clinical model of HIV infection. Our results show strong HIV inhibitory activity in serum, cervicovaginal secretions and saliva obtained from animals after a single oral dose of EFdA demonstrating efficient drug penetrance into highly relevant mucosal sites. Importantly, a single daily oral dose of EFdA resulted in efficient prevention of vaginal and oral HIV transmission after multiple high-dose exposures to T/F viruses, offering in vivo pre-clinical data supporting the use of EFdA as a pre-exposure prophylaxis (PrEP) agent to prevent HIV infection in both women and infants.
Conclusions: Significant gender inequalities limit the ability of women to access and exercise HIV prevention options resulting in earlier acquisition of infection, higher transmission rates and increased mother-to-child transmission of HIV. Our results demonstrating excellent efficacy in preventing both vaginal and oral HIV transmission together with EFdA''s relatively low toxicity and high potency against drug-resistant HIV strains support its use in both women and infants, the two of the most vulnerable populations at risk for acquiring HIV.