Aids Prevention and Treatment

The lifecycle of HIV is shown in Fig 3.2. Initial interaction between the viral coat glycoprotein gpl20 and the glycoprotein called CD4 on the T-lymphocyte or macrophage is followed by an additional binding to a co-receptor called 

Once inside the host cell, the virus loses its coat and the two single (+)-strands of viral RNA are released together with the enzymes viral reverse transcriptase (RT), integrase and protease. RT is an RNA-dependent DNA polymerase and is needed to catalyse the transcription of the genetic information present within the RNA into viral DNA, and thence production of double-stranded DNA. The new pro-viral DNA is now incorporated into host cell DNA using the enzyme viral integrase, and this incorporated DNA 

The immune system does mount a vigorous response in these early days. Macrophages ingest the viral particles and degrade them, and then display small portions of the virus (small peptides called epitopes) on their surface, and this attracts the attentions of helper T-cells, which in turn activate killer T-cells and B-lymphocytes. The killer T-cells attack cells displaying the viral epitopes, and the B-cells produce dedicated antibodies that also seek out and destroy such cells. Not surprisingly, in the early days after infection, around 30% of patients exhibit typical symptoms of their immune response to viral 

Over a period of time, these CD4-positive T-cells are destroyed, as much by the activated killer T-cells as by the virus itself, and the loss of these cells is evidenced by the lowering of the numbers of detectable CD4-positive cells. These should normally number around 800-1200 per cubic millimetre of blood, but this count drops initially to around 500 in HIV-positive patients and then to less than 200 in patients with full-blown AIDS. This process may take a few years, but typically takes around 10 years. 

There are also now a number of non-nucleotide reverse transcriptase inhibitors and the most useful of these are nevirapine (Viramune, 1996) and delaviridine (Rescriptor, 1997), which appear to act at an allosteric site close to the active site of RT. This means that they block the subtle (and apparently essential) changes in the three-dimensional structure that occur when nucleotide substrates bind to the active site of RT. 

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NS AIDS Prevention and treatment of post-operative pain Diclofenac, ibuprofen... 

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