While it is now possible to prolong life in HIV infected individuals with antiretroviral treatment, two basic questions remain. When to start treatment and what treatment is preferred initial therapy. Enthusiasm for starting treatment as soon as HIV is diagnosed has been tempered by the realization that present treatment cannot eradicate infection, and is associated with long term toxicity. Furthermore treatment in late disease results in sufficient immune reconstitution to prevent opportunistic infection. In the absence of strategic studies to answer the question of when treatment should start, a pragmatic risk benefit analysis is now made which takes into
account the likelihood of development of clinical events, the ability to adhere long term to therapy and the likely toxicities. Such risk benefit analysis is aided by cohort studies suggesting that survival is worse in individuals first treated when their CD4 count is below 200 cells mm-3. In contrast the viral load at start of treatment is a poor discriminator of short term survival. Other cohort studies also suggest that the ability to reduce plasma viral load to undetectable levels is less good in individuals first treated when the CD4 count is below 200 cells mm-3. Prospective strategic studies are required to define the optimum starting point. When the various studies leading to licensure of drugs used in combination are compared,
relatively similar results in terms of the ability to reduce viral load below detectable limits at 48 weeks+ are obtained. It is not clear that perceived minor differences in such results should guide the choice of initial therapy. It is more likely that treatment should begin with drugs with which long term adherence is possible, which produce minimal side effects and which are “forgiving” in terms of occasional late dosing. It is recognized that most individuals will require more than one regimen during their lifetime and the ability of the first regimen to be successfully salvaged by a second would also be an important aspect of choosing therapy. Again strategic studies are now addressing this issue.
|
