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Highlights of the 5th International Workshop on Clinical Pharmacology of HIV Therapy

Authors: David M. Burger, PharmD, PhDFaculty and Disclosures

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Introduction

More than 180 clinical pharmacologists, virologists, physicians, and industry researchers convened at the Università Cattolica del Sacro Cuore, Rome, Italy, for the first "lustrum" of this meeting. After the first 2 meetings in Noordwijk, The Netherlands, and subsequent meetings in Washington, DC, and Cannes, France, this workshop has now evolved into the most important meeting in the highly specialized field of HIV pharmacology. A record number of 82 abstracts were presented, including over 30 oral presentations by both young scientists and well-known experts in the field, together with 6 invited lectures on hot topics in HIV pharmacology, such as triple-nucleoside therapy failures, pharmacologic considerations in HIV-infected patients coinfected with hepatitis B/C, gender and ethnicity differences, entry inhibitors, and more. This report provides a summary of the most relevant presentations; all abstracts and most presentations can be accessed at the organizers' Web site: www.virology-education.com.

Pharmacologic Considerations in Developing Countries

Dr. Andrew Hill,[1] who has a part-time position as a visiting research fellow at Liverpool University, Liverpool, United Kingdom, kicked off with a presentation titled "MicroHAART." Hill described evolution of the "hit hard, hit early" paradigm to what can now be called MicroHAART (or "adjusted HAART" [highly active antiretroviral therapy] as some may prefer). As we may have faced an upper limit in antiviral activity (at least in treatment-naive patients), the limiting factors for long-term success of a regimen are adverse events and nonadherence. Dr. Hill mentioned data from the ICONA Cohort that indicate that these 2 factors combined are the cause of drug discontinuation in almost 80% of patients. This suggests that improving the safety profile of HAART may be an effective strategy to improve adherence and treatment outcome. Hill described data on 7 antiretroviral drugs (zidovudine, lamivudine, stavudine, indinavir, lopinavir, ritonavir, and efavirenz) for which it can be questioned whether the current maximum tolerated dose is actually the minimum effective dose (Figure 1).

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Adapted from: Hill A. MicroHAART. Program and abstracts of the 5th International Workshop on Clinical Pharmacology of HIV Therapy. April 1-3, 2004; Rome, Italy. Plenary talk.

MicroHAART could be applied as either lower doses of HAART regimens, less frequent dosing of some components of a HAART regimen, or constructing HAART regimens with less than 3 drugs. The main caveat of this approach is that development of resistance may outweigh the improved tolerability of MicroHAART regimens. It was concluded that these approaches are considered to be highly experimental, and they should only be evaluated in research settings. If MicroHAART is proven to show equivalent efficacy compared with current HAART regimens, it would likely increase access to HAART regimens in developing countries.

In a subsequent talk, Dr. Francesca Aweeka[2] from the University of California, San Francisco, discussed how different the epidemiology of HIV is in developing countries compared with the Western world. Women present more than 50% of the infected population in developing countries vs only 25% and 20% in the United States and Europe, respectively. Dr. Aweeka described what is currently known regarding gender effects on the pharmacokinetics of antiretroviral agents. For a number of drugs, such as nevirapine, indinavir, saquinavir, lopinavir, and enfuvirtide, higher plasma levels have been observed in female patients than in male patients, whereas conflicting data exist on efavirenz. Ethnicity influences are more difficult to investigate because genetic differences are usually observed in relatively small numbers of subjects and may be confounded by other factors, such as body weight, gender, and food effects. Recent data indicate higher efavirenz levels and more central nervous system toxicity in black patients. As access to HAART regimens in Africa increases, it is clear that further research is needed on this topic.

After these 2 invited lectures, 2 oral abstract presentations were given on HAART regimens in advanced-stage, indigent patients in the ESTHER program in Rwanda[3] and on lopinavir pharmacokinetics in Caribbean HIV-infected patients.[4]

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