History
It was under development by ViiV Healthcare / GlaxoSmithKline for use in the treatment of HIV infection. When the active form of fostemsavir binds to the gp120 protein of the virus, it prevents initial viral attachment to the host CD4+ T cell and entry into the host immune cell; its method of action is a first for HIV drugs. Because it targets a different step of the viral lifecycle, it offers promise for individuals with virus that has become highly resistant to other HIV drugs. Since the function of gp120 that this drug inhibits is highly conserved, the drug is unlikely to promote resistance to itself. Investigators found that enfuvirtide-resistant and ibalizumab-resistant HIV envelopes remained susceptible to fostemsavir. Conversely, fostemsavir-resistant HIV remained susceptible to all the entry inhibitors. Furthermore, HIV isolates that do not require the CD4 receptor for cell entry were also susceptible to fostemsavir, and the virus did not escape the attachment inhibitor by becoming CD4-independent. Prior in vitro studies showed that fostemsavir inhibits both CCR5-tropic and CXCR4-tropic HIV. Fostemsavir was approved for medical use in the United States in July 2020.The safety and efficacy of fostemsavir, taken twice daily by mouth, were evaluated in a clinical trial of 371 heavily treatment-experienced adult participants who continued to have high levels of virus (HIV-RNA) in their blood despite being on antiretroviral drugs. Two hundred seventy-two participants were treated in the main trial arm, and an additional 99 participants received fostemsavir in a different arm of the trial.
Vesicouterine fistula refers to an abnormal communication between the bladder and uterus. The first case of vesicouterine fistula was reported in 1908. It was however first described in 1957 by Abdel Fattah Youssef, an obstetrician and gynaecologist in Kasr el-Aini hospital, Cairo, Egypt. It is characterized by a vesicouterine fistula above the level of the internal os, absence of menstrual bleeding, cyclical presence of blood in urine and absence of urinary incontinence with a patent cervical canal following a lower segment caesarean section. Six of such cases had been reported by other clinicians before the term Menouria was coined by Youssef. Pathology
Vesicouterine fistula is the least common type of urogenital fistula accounting for 1-4% of urogenital fistulas. It occurs following lower segment caesarean section and the incidence is increasing due to the increasing incidence of caesarean deliveries. The occurrence of menoruria in the absence of vaginal bleeding or passage of urine from the vagina is attributed to a sphincteric mechanism of the uterine isthmus.Jozwik and Jozwik classified vesicouterine fistula into three types based on the route of menstrual flow;I - Menstrual flow from the bladder only without urinary incontinence
II - Menstrual flow from both the bladder and vagina with urinary incontinence
III - Normal menstrual flow from the vagina only (no menouria) with urinary incontinence
Youssef syndrome corresponds to a type I vesicouterine fistula. Causes
Vesicouterine fistulas occur most commonly after lower segment caesarean sections (about 83-93% of cases).