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
"Initiating Antiretroviral Therapy (Why, When and How to Initiate Antiretroviral Therapy)" Dr. Jose Gatell (biography) English - 2002-04-14 - 39 minutes
Summary : Like a Marathon run, antiretroviral therapy is a business for life. In fact, is a long life 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 athletes 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 response rate rarely, if ever, exceeds 50% at 24-48 weeks using an intent to treat analysis (in general missing = failure). Yet, while the efficacy of some antiretroviral regimens have never been tested or proved beyond 48 weeks, other regimens have already shown a substantially greater response rate with a sustained durability up to 3-6 years even using the most stringent intent to treat analysis (non completers = failure). Several years ago we have learnt that even small and transient perturbations in the replicative capacity of the 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 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 clinical lipodystrophy and other mid and long term side effects, 2) the complexity, inconveniences and restrictions associated with some of the most useful and widely used antiretroviral regimens and, 3) the ability to achieve a sufficient degree of self reconstitution of the immune system even when antiretroviral therapy is initiated in late stages of HIV-1 disease.
No randomized studies have addressed the question of when to start in the era of HAART. However the analysis of several, but not all, cohorts highlights to the fact that the greatest and most evident clinical benefit is obtained 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 the strongest marker of lack of clinical progression or death. Conversely, apart from common sense there are 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. Long term potential for toxicity (mainly metabolic disturbances and lipodystrophy) may be lower with these newer regimens. Moreover, within next months it should be possible to construct simple and potent regimens able to be administered once per day, eventually directly supervised, and with a lower potential for long term toxicity.
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