The profusion of HIV conferences dilutes the quality of the data and keeps us from our day jobs. Next year’s XVI International AIDS Conference will be held in Toronto (which is only a little farther from Baltimore by plane than the Brazilian conference center was from Rio by bus!). In between, we’ll have ICAAC, IDSA, EACS, and CROI, not to mention smaller meetings devoted to lipodystrophy, resistance, and pharmacology, just to name a few. Still, it’s encouraging to look back over a year’s worth of data, as spread out as it is, and realize that steady progress is being made in the management of HIV infection.
TMC114 and GW695634 are promising agents in the pipeline for salvage of PI-resistant or NNRTI-resistant virus, respectively. Dd4FC appears to have more modest activity against NRTI-resistant virus. Three CCR5 inhibitors are currently in clinical phases of development, and demonstrate promising activity. A new tablet formulation of LPV/r is expected to simplify the use of this drug, and will make once-daily dosing more feasible.
There continues to be controversy about the development of NVP resistance when this drug is used for prevention of mother-to- child transmission. Despite presentations on the subject at this and other meetings, the subject is far from settled, and randomized trials and observational studies are ongoing or planned that will further explore this critical issue.
There was substantial emphasis on prevention at the 3rd Annual IAS meeting in Rio de Janeiro, with multiple featured presentations, oral abstracts and posters; but there was far more smoke than fire. The statistics continue to be staggering. In 2004 were 39.4 million persons living with HIV infection, 4.9 million new infections, and 3.1 million deaths [Piot P, Abstract WeSl01]. These figures are 50% higher than the 1991 projections from the World Health Organization.
Janet M. Siliciano, Ph.D. and Robert F. Siliciano, M.D., Ph.D.
The demonstration that HAART could lower plasma virus levels to below the limit of the detection raised hopes that eradication could be achieved with prolonged therapy [Perelson AS, et al. Nature. 1997 May 8;387(6629):188-91]. However in recent years, there has been little discussion of a cure for HIV infection. Shortly after the advent of HAART, several groups showed that the virus could persist in a latent form in resting memory CD4 cells even in patients who had no detectable viremia for prolonged periods of time as a result of HAART [Finzi D, et al. Science. 1997 Nov 14;278(5341):1295-300; Chun TW, et al. Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):13193-7; Wong JK, et al. Science. 1997 Nov 14;278(5341):1291-5].
The most eventful aspect of the 3rd IAS Conference in Rio de Janeiro for me was a missed connection and lost luggage for three days. However, we did deepen our understanding of fat and metabolic issues. And, of course, the weather and the Brazilians were beautiful.
The International Workshop on the Clinical Pharmacology of HIV Therapy was founded six years ago as a forum for the exchange of primary data to better understand the disposition and rational use of antiretroviral drugs. Since then, the meeting has grown from a small rehash of CROI to a major international meeting in its own right, attracting over 200 participants and more than 100 presented abstracts. This is now pharmacology’s equivalent of the annual Resistance Workshop, which interestingly is organized by the same company.
Treatment advances have led to an increased prevalence of HIV infection in the United States over the past decade. Parallel advances in the “science” of HIV prevention and their thoughtful application will be required to prevent the continued spread of HIV infection.
The handful of studies on antiretroviral therapy that were presented at ICAAC this year helped us to learn more about the growing number of options for initial therapy and shed light on several promising investigational agents. We can expect to learn much more at the upcoming Conference on Retroviruses and Opportunistic Infections, to be held in February, 2005 in Boston, which will be extensively covered in The Hopkins HIV Report.
Todd Brown, M.D. and Joseph Cofrancesco, Jr., M.D., M.P.H.
The complexity of HIV-associated complications is apparent. This workshop shed further light on the role of specific antiretroviral agents or classes of agents in the emergence of these complications. Although insulin resistance is often thought of as a complication associated with protease inhibitors, there are clear differences among the PIs, and nucleoside analogs may also play a role. Ritonavir-boosted fosamprenavir or atazanavir appear to have only minimal effects on insulin resistance and lipid elevations. The data continue to implicate thymidine analogs, particularly stavudine, in causing mitochondrial damage and resulting clinical syndromes. Switching from another NRTI to tenofovir or abacavir may help with these complications.
On October 29, 2004, the DHHS released the most recent version of the federal guidelines for use of antiretroviral agents in HIV-infected adults and adolescents. Guidelines for use of anti-retroviral agents in HIV-1-infected adults and adolescents [Panel on Clinical Practices for Treatment of HIV Infection, Department of Health and Human Services (DHHS)]: This is a draft version posted on the AIDSInfo web site, http://AIDSinfo.nih.gov, with a request for comments, which should be sent to aidsinfowebmaster@aidsinfo.nih.gov. This document has been entirely rewritten.
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This information is designed to support, not replace, the relationship that exists between you and your doctor.