February 26, 2002
Drug addicts are one of the most difficult populations to reach. It is not only difficult to disseminate messages about HIV prevention but sometimes there is also the perception -- frequently not real -- that people who are addicted to drugs will not be compliant with combination regimens.
In this study, Brian Conway's group in British Columbia compared the efficacy of once-a-day vs. twice-a-day antiretroviral regimens in drug abusers enrolled in their methadone clinic. This was not a randomized trial (i.e., the clinician and the patient decided which regimen to get and the schedule they preferred). This design, although simpler for the clinic and the patient, has many potential biases because it is likely that patients with perceived problems of adherence would be more likely to get the once-a-day regimens, and that difference might explain some of the results of the study.
Nevertheless, in this era of once-a-day regimens, it is important to know how they work in these difficult-to-reach populations because, if they work well with this population, in theory they should work with anyone. Also once-a-day, directly-observed therapy strategies could be used as models in the developing world.
The study included 54 patients with a relatively high viral load of 210,000 copies/ml and a baseline CD4 T cells of 200 cells/mm3. The patients were followed for 24 months.
In general, the responses were comparable between NNRTI-based regimens (mainly nevirapine-based) and protease inhibitor-based regimens. There were also no differences between once-a-day regimens and twice-a-day regimens. The power to make these comparisons is limited, mostly because of the lack of randomization, and the small sample size. In any case, it does not appear that there was a big difference in adherence between these two regimens, either.
One of the important messages of the trial is that therapy worked for a very significant proportion of patients (65%, less than 400 copies of HIV RNA per ml), and this is in spite of the fact that all patients were active drug abusers and were enrolled in a methadone clinic.
Drug abuse is a very significant problem with adherence. Though adherence is commonly the most important predictor of success when patients need antiretroviral therapy, we might be overestimating its power. Linking antiretroviral therapy to the administration of methadone increases the success of reaching this population and seems like one of the best strategies for this group of patients with very complex problems.
Treatment of HIV in drug abusers has also always been complicated by the presence of interactions between drugs like methadone and NNRTIs. Nevirapine, for instance, greatly reduces the levels of methadone in the body, which can lead to symptoms of withdrawal. Physicians dosing nevirapine with methadone should expect an increased requirement of methadone in this population and address this issue aggressively. If not, there is a high chance that the patient will have withdrawal symptoms and abandon the treatment for two of his/her most significant medical problems: drug abuse and AIDS. An average 45% increase in methadone dose was required to counter the associated withdrawal symptoms in patients receiving nevirapine concomitantly. Many pharmacokinetic studies have confirmed this interaction.
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