Uman immune system, such as T helper cells (specifically CD4+ T cells), macrophages, and dendritic cells. HIV entry into the host cell is initiated by the binding of the envelope protein gp120 to a set of molecules present over the host cell surface, comprising the primary receptor CD4 and a coreceptor, usually either CCR5 or CXCR4.213 HIV preferentially uses CCR5 during the acute phase of infection, but switches to CXCR4 later as the disease progresses in approximately 50 of patients.24 After the initial binding of gp120 with the CD4 receptor present on the target cells, it is further stabilized by the heparan sulfate proteoglycans present on the host cell surface. This binding induces a conformational change in the gp120, exposing sites that interact with the chemokine receptor (CCR5 or CXCR4). The virus-fusion protein (gp41) then gets uncovered and undergoes a conformational change. Glycoprotein gp41 inserts itself into the membrane of the host cell to initiate the fusion of the two bilayers. Viral RNA released into the cytoplasm undergoes reverse transcription with the help of the RT enzyme and is convertedinto DNA. This viral DNA enters the host cell nucleus, where it integrates in the host genetic material by the integrase enzyme. The integrated genome of HIV may lay dormant, until cellular transcription factors enhance transcription of the viral genome and trigger the production of viral proteins. HIV gene transcription from the integrated viral DNA (known as provirus) requires several host and viral proteins.Sugemalimab The assembly and release (known as budding) of HIV from the host occurs in a series of organized steps that are driven by the viral gag protein.25 Once the immature and noninfectious virus particles are released from the cell, further processing of gag polyproteins by HIV protease leads to the generation of mature infectious virus particles.Zanidatamab Microbicides have been developed aiming to interfere at various stages of HIV-1 virus life cycle, as shown in Figure 1.PMID:23460641 The establishment of infection at the portal of entry and timing of dissemination might also be affected by the number and types of cells that are initially infected. During male-tofemale sexual transmission of HIV following ejaculation, HIV , is believed to remain infectious in semen for several hours, although the precise duration is not known.26 During this time, diffusion is likely to be a principle mechanism of HIV transport from semen to vaginal epithelial surfaces. HIV-infected cells present in the semen can also cross the epithelial barrier, leading to transmission of HIV infection (transmigration). The available data suggest that susceptibility to HIV can be enhanced in the presence of an ulcerative STI, either through mucosal disruption or through increased number or activation of cells susceptible to HIV 27 Nonulcerative infections have . also been linked to increased susceptibility to HIV infection by triggering the proinflammatory responses that enhance viral replication or by proliferation of HIV-susceptible cells.28 Based on their active properties, microbicides can be broadly classified into four categories: (1) inactivation of the virus; (2) inhibition of virus binding, fusion, or entry to the susceptible host cell; (3) inhibition of HIV replication in the host cells; and (4) maintenance or enhancement of the vaginal defense (Figure 1). Table 1 summarizes some of the microbicides that have undergone clinical trials in humans and the outcome of their e.