Important note: Information in this article was accurate in October 1999. The state of the art may have changed since the publication date. | The online version of HEPP News displays the main article only, to view the entire newsletter download the following PDF:
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The 39th annual Interscience Conference on Anti-microbial Agents in Chemotherapy (ICAAC) was held in San Francisco September 25-29, 1999. From the correctional perspective, some of the most relevant HIV related topics that were discussed include: longer term follow-up of some previously reported highly active antiretroviral (HAART) trials, genotypic and phenotypic resis-tance testing, discontinuation of opportunistic infection (OI) prophylaxis, further elucidation of host factors involved in the immune response to HIV, and troubling information regarding side effects of HAART. One common theme was that the most important predictor of achieving an undetectable HIV viral load (VL) is patient adherence to therapy. In spite of glowing reports from some clinical trials, the fact remains that approximately 40% of previous-ly treatment naïve patients receiving HAART will experience virologic failure within one year. Nationwide, about one third of patients on > 3 agents have HIV VL >20,000. The proportion of patients who will maintain an HIV VL of < 400 drops precipitously when adherence falls below 95% (i.e. missing 1-2 doses per month). Understanding that a major predictor of a patient's adherence to therapy is trust in his or her clinician, it is crucial to implement approaches in correctional settings that allow effective patient education and foster trusting relationships with clinicians. Correctional providers should take the time to carefully review treatment options with their patients, since the initiation of HAART is rarely an emergency, and the second regimen rarely works as well as the first.
This month's report from ICAAC will review HAART trial reports and HIV resistence testing.
Next month's report will discuss updates concerning opportunistic infection side effects and host factors.
Longer-term data on multiple clinical trials was presented and demonstrated a clear role for non-protease inhibitor (PI) containing regimens in the initial treatment of ART naïve patients. Brief synopses follow:
When considered together, the above studies provide strong evidence for the efficacy of PI sparing regimens utilizing either 3 NRTIs or 2 NRTIs plus 1NNRTI in ART naïve patients. This data suggests, however, that triple nucleoside regimens perform less well in those with baseline HIV VL's of >100,000 (see also our Expert Opinion on intensification, by HEPP editor Rick Altice - on page 4). Non PI containing-regimens involve fewer pills, fewer doses, and often less side effects - all factors which can help improve adherence. Data also revealed that EFV/dual nucleoside regimens are as effective as those containing PIs in reducing HIV replication in sanctuary sites such as lymph nodes.
Much less hopeful information was presented on salvage regimens for those failing multiple other treatment combinations. Follow-up data on "Mega HAART" (>5 drugs) guided by genotypic analysis revealed response rates (VL<400) in about 1/3 of patients over the short term. Mega motivated patient. Response rates to salvage therapy were related to patient adherence, pre-treatment VL and the use of a new drug class.
A major focus at ICAAC was the role of HIV resistance testing in clinical practice. In spite of significant limitations of the current methodologies, it is clear that resistence testing will soon be considered standard of care. Genotypic analysis attempts to identify the viral mutations known to be most important in predicting resistance to ART. Phenotypic analysis is analogous to antimicrobial resistance testing, where "resistant" is generally defined as ten times the IC 90 of the virus. Both methods are expensive and time consuming. It is likely that over the next year, costs and turn around times will fall, making testing more accessible. Two studies were discussed which attributed improved patient outcomes (as measured by HIV VL) to the use of resistance testing. A 12-week analysis of the GART study revealed a benefit to genotypic analysis coupled with expert opinion as opposed to standard care. The latest analysis of the VIRADEPT study demonstrated ongoing clinical benefit to the use of resistance testing at 12 months of follow-up.
VIRADEPT also analyzed serum PI levels and found that they correlated with virologic outcomes. This data raises the question of whether drug levels will eventually become an important part of our treatment strategies. There was considerable discussion concerning the substantial variability in reliability of resistance testing from one lab to another. Other data demon-strated that patients who experience virologic failure to HAART are often resistant to only one drug in their regimen. In this setting, resistance testing would help prevent the "discarding" of agents that retain efficacy.
Finally, a number of abstracts pointed out the significant baseline levels of genotypic and phenotypic resistance in untreated (naïve) patients. As with tuberculosis, it may become important to know the prevalence of resistant virus circulating in your patient population prior to selection of an initial regimen.
PI sparing stands for protease inhibitor sparing, or antiretroviral combinations that do not include a protease inhibitor.
Intent to Treat (ITT) Analysis versus As Treated (AT) Analysis When evaluating the results of a clinical trial, in the ITT analysis, if a patient starts on one combination and then quits (for any reason) they are counted as a treatment failure. In the AT analysis, the data is evaluated based upon the success of what the patient is actually taking.For example, consider two different treatments. One works in 100% of the people but is so dreadful that only 10% of patients can stay on it. A second treatment works in only 80% of the people, but is much more tolerable. If the two treatments were compared, the type of analysis used would lead to different interpretations. In the as treated analysis, the therapy that only 10% of the people could stay on would look better because those who stayed on it all did well. In the intent to treat analysis, the therapy that worked 80% of the time but was much more tolerable would be graded better.
1999-1010
HEPP1999-1001
©1997,1998,1999,2000. The recently formed HIV Education Prison Project (HEPP) is a medical education program that targets a growing population, inmates in correctional facilities, that has been underserved in HIV care. It is part of the Brown University AIDS Program. Permission to use and reproduce portions of this newsletter is hereby granted provided that author and publication are fully credited and both copyright and permission notice appear with reprinted material. Inquiries may be directed to heppnews@brown.edu. Website: HIV Education Prison Project.
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