CMEonHIV.com is dedicated to providing online CME presentations (slides with voiceover) on HIV/AIDS for healthcare professionals given by local and international experts to keep you up-to-date on the ongoing developments in the field.
Conference
"Initial Therapy" Dr. Jose Gatell (biography) English - 2003-03-29 - 50 minutes
Summary : Like a marathon run, antiretroviral therapy is a business for life. In fact, is a life long therapy because HIV-1 eradication at present is not an achievable objective and supervised or structured therapy interruptions (STI`s) or immune based therapies still remain in the domain of clinical research. Not all athlestes are equally fitted to participate in marathons and only a few of them can expect to have some chances of winning. The same is true for antiretroviral regimens. Some unfair across studies comparisons have lead to the easy and superficial conclusion that the response rate, if ever, exceeds 50% at 24-48 weeks using an intent to treat analysis (in general missing = failure). Yet, while the greater response rate with a sustained durability up to 3-6 years even using the most stringent intent to treat analysis (non-completers = failure) and some of them with a fairly acceptable tolerance. Just to mention a few examples regimens already available like ZDV + 3TC + Efavirenz Kaletra or Tenofivir + 3TC + Efavirenz fulfill these requirements and atazanavir containing regimens may be a future option implying a smaller proportion of patients with metabolic abnormalities requiring lipid lowering agents.
Several years ago we have learnt that even small and transient perturbations in the replicative capacity of HIV-1 can dramatically influence the natural history of the disease. Moreover, a sustained suppression of the viral replication quickly translated into an immunological reconstitution a delay in the disease progression and ultimately in a much prolonged survival. Recommendations about when and how to initiate antiretroviral therapy have dramatically shifted to more conservative positions during the past 1-2 years switching from the principle of hitting “early and hard” to hitting “not too late and wisely”. The major driving forces for these changes have been 1) the realization of the high incidence of metabolic disturbances and clinical lipodystrophy and their potential consequences on mid and long term cardiovascular events and other mid and long term events, 2) the complexity, inconveniences and restrictions associated with some of the most useful and widely used antiretroviral regimens, and 3) the ability to achieve an apparent sufficient degree of self reconstitution of the immune system even when antiretroviral therapy is initiated when the CD4+ cell count drops below 200 cells per microliter or even lower and being the adherence to prescribed therapy and the levels of physician experience strongest markers of clinical pregression or death. Conversely, apart from common sense there a number of biological, virological and immunological reasons to initiate antiretroviral therapy in much earlier stages of HIV-1 disease providing a potent, durable, convenient and save antiretroviral regimen is available.
The paradigm about composition of initial antiretroviral regimens shifted about 2-3 years ago from PI containing regimens to PI sparing regimens (namely 2NRTI + 1NNRI) and most recently even to 3NRTI (less effective regimens). Particularly the 2NN study has shown non-inferiority of a nevirapine containing triple therapy as compared with efivirenz. Long term potential for toxicity (mainly metabolic disturbances and lipodystrophy) may be lower with some of these newer regimens. Moreover, it is already possible to contrust simple and potent regimens able to be administered once per day, eventually directly supervised. With such regimens we may try to better target hard to reach population like IVDU or those with lower socioeconomical status.
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