The Body Covers: The XIII International AIDS Conference
Switching Antiretroviral Regimens
July 12, 2000
In the session today, and during the conference in many posters I've seen, we saw a little bit of both. Today's oral sessions, however, did not bring big news.
A randomized, controlled, open-label study comparing the adherence and convenience of continuing indinavir Q8H vs. switching to norvir/indinavir 400 mg/400 mg BID (The NICE study) (WeOrB482)This session included two presentations about adding RTV to an indinavir-containing regimen. The first one of these presentations by Dr. DeJesus, (WeOrB482) randomized patients who were taking IDV to continue IDV q8h (n=79) or switch to RTV 400 BID plus IDV 400 BID (n=301). DeJesus presented preliminary data generated from analysis of an adherence questionnaire completed by study participants at week four of the study in 275 patients in which data was available. The switch both improved adherence and patients' perceptions concerning the difficulties of taking the medications. This leads to less missed doses and improvements in taking the medication on time. DeJesus did not present any virology data, which is reserved for the final analysis. One unexpected finding was the very high dropout rate in the indinavir control arm (15% in four weeks vs. 14% in the RTV/IDV arm). No clear explanation was provided for this, but perhaps it is related to the fact that some patients were unhappy with the arm in which the randomization process had placed them.
A randomized study comparing continued indinavir (IDV) (800mg TID) vs. switching to indinavir/ritonavir (RTV) (800/100mg BID) in HIV patients having achieved viral load suppression with indinavir plus two nucleoside analogues. The BID efficacy and safety trial (BEST) (WeOrB484)The second study was a European multicenter study presented by Dr. Gatell from Barcelona (WeOrB484). In this study 326 patients were randomized to continue IDV (n=165) or switch to RTV 100mg BID and IDV 800mg BID (n=161). The presentation focused on the 237 patients that have reached six months of follow-up after the switch. Approximately 90% of the subjects maintained viral suppression. However -- and this was the surprise of the presentation (at least for me) -- the tolerability was worse than I expected with low-dose RTV.
The table summarizes the adverse events observed:
Efficacy of protease inhibitor switching to nevirapine in patients on HAART with undetectable viral load (WeOrB485)Dr. Miguel Gorgolas from Madrid presented data about 110 patients who switched the PI of their fully suppressive regimen to nevirapine. The median CD4 at the time of the switch was 603 cell/mm3. 90% of the patients remained undetectable at week 48, although not all patients have reached that point yet. Twenty-three patients discontinued nevirapine before that point (the reasons were: lost to follow up, withdrawal of methadone, hepatitis, increased LFTs, rash, and viral rebound in only five patients). Triglycerides decreased markedly and the total cholesterol also decreased to a more moderate degree. No data on other metabolic complications was presented at this time.
Diane Havlir gave a great summary of "switches" at the end. She classified the switches in two ways -- the first as "reactive," (i.e., to treat virologic failure or severe toxicity), and the second as "preemptive" (i.e., to increase the potency of the regimen (intensification) in order to reduce toxicity or to improve adherence). She stated that there is a growing body of evidence showing that switching form a PI to an NNRTI is virologically safe, although more prolonged follow up is needed to understand all the metabolic implications of switching.
Overall, the practical implications of these and other presentations, is that switching is a reasonable strategy only if it does not sacrifice potency, since any improvement in tolerability leads to increased durability of the antiretroviral response (which is as critical as potency to assure the long-term success of any treatment).
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