Even in subjects with HIV replication well controlled by therapy, 70% have detectable plasma viremia which does not appear to decay over time (at least two years). To improve the sensitivity of the assay for HIV, 4 billion lymphocytes are mixed with antibody attached to magnetic beads. This selects for the CD4+ T cells, about 0.2–1 billion cells. The limit of detection is 1 copy of HIV RNA/million cells, MEK inhibitor limit of quantitation is 10 copies/million cells. To reduce the reservoir of HIV, it was suggested that activation of integrated HIV in resting CD4+ T cells would give renewed HIV RNA synthesis and possibly result in cell death either
due to viral cytopathic effects or resulting from HIV-specific immune responses. A small clinical trial was set up to test this hypothesis. Vorinostat (VOR), a clinically approved drug for treating certain cancers, has been shown to bind to the active site of histone deacetylases. After a single dose, there was an increase in HIV RNA (1.5 to 5-fold, mean 2.6-fold). Of these subjects, 5 elected to continue with multiple doses. From the
11th to 22nd VOR dose, acetylation of histones and activation of HIV RNA synthesis became refractory to therapy. Also, it is not known what proportion of cells, with latent HIV, can be activated. Whereas a single VOR dose did increase the expression of HIV RNA, this is not an effective therapy for removing the HIV reservoir. Myron Cohen, University of North Carolina, NC, USA Myron noted that there are 2.5 million Ion Channel Ligand Library chemical structure new HIV infections each year. In this context, anal sex may ADAM7 be an important factor because just one
or a few virions of HIV can be infective; within 3 weeks, there is rapid virus replication throughout the body and latent HIV reservoirs of “founder virus” are already formed. Although anal sex has been associated with homosexual couples, Myron pointed out that it is not uncommon amongst heterosexual couples. Although behavioral education should be encouraged, it can never be the whole answer. Various approaches to the prevention of HIV transmission are being evaluated. Monoclonal antibodies, broad neutralising antibody (bNAB) and vaccines may have potential for prevention of transmission, but most progress is being made with dapivirine rings containing TDF. These are designed to stay in the vagina for a month. Phase III trials are ongoing. A long-acting HIV integrase inhibitor, GSK 1265744 (generally known as GSK 744), is administered i.m. once every 3 months; a two-year safety trial will be required. Phase I trial has been completed and Phase II trial is being planned. By analogy with tuberculosis therapy, in which the infectious state is disabled prior to a complete cure, one wonders if HIV transmission rates may decrease with effective ART use.