[PL-2] CURRENT CONTROVERSIES IN ANTIRETROVIRAL AND POTENTIAL SOLUTION: TRANSLATING SCIENCE INTO ACTION.

1st International AIDS Society Conference on HIV Pathogenesis and Treatment

Buenos Aires, Argentina - July 8-11, 2001

[TITLE:] CURRENT CONTROVERSIES IN ANTIRETROVIRAL AND POTENTIAL SOLUTION: TRANSLATING SCIENCE INTO ACTION.

[AUTHOR(S):] Julio S.
G. Montaner BC Centre for Excellence in HIV/AIDS, St. Paul's Hospital, University of British Columbia, Vancouver, Canada

IAS Conf HIV Pathog Treat 2001 Jul 8-11;1st: Abstract No. PL-2

[ABSTRACT:] The management of HIV infection has radically changed since 1996 when triple drug antiretroviral therapy regimens were first shown to be clinically effective. Widespread use of such regimens has led to dramatic decreases in mortality and morbidity in multiple cohort-based studies typically conducted in developed nations of the world. Recently, it has become apparent that eradication of HIV infection with current therapies may not be readily attainable. Also, long term side effects have emerged as a new challenge. Furthermore there has been increasing evidence that the ability of the immune system to reconstitute is greater than originally perceived. This may have important implications in optimizing the use of antiretroviral therapy, particularly in view of the current effort to expand access to antiretroviral therapies worldwide.

The optimal time to initiate antiretroviral therapy remains to be established. Ideally, this should be settled through the conduction of long term, prospective, controlled randomized strategy trials. Unfortunately given the rate at which antiretroviral therapy is evolving such an approach may not be feasible.

Recent work suggests that short-term (2-3 years) morbidity and mortality benefits of antiretroviral therapy can be fully preserved as long as treatment is initiated at CD4 counts >200/mm³, regardless of plasma HIV-1 RNA levels (among AIDS-free individuals). More recently, high level of clinical effectiveness was demonstrated in highly compliant individuals initiating treatment with CD4 s >50/mm³ regardless of plasma HIV RNA levels. If independently confirmed, these data may be useful in optimizing the implementation of antiretroviral therapy program, particularly in resource limited settings.

Emerging toxicities of antiretroviral therapy remain a significant concern. Nucleoside related mitochondrial toxicity has become a growing concern in this context. The recent development of a semiquantitative mitochondrial DNA assay may allow for the early identification of this toxicity.

Taken together these developments suggest that further optimization of antiretroviral therapy may be achieved by strategic targeting of such programs, as well as optimizing their safety. It should be stressed, however, that with the increasing complexity of HIV management the success of such programs will be highly dependant on the development of appropriate infrastructure, specifically including adherence support for HIV infected individuals and ongoing treatment and education for their treaters.

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