Retrovirus & Opportunistic Infections (cont.)

Treatment Simplification

Maintenance therapy is one strategy for reducing pill burden and toxicity, while another is to switch the type of therapy to a regimen that might be easier to take with less adverse events. A previously reported study called "NEFA" simplified therapy from a PI-containing regimen to one of two NNRTI regimens with efavirenz or nevirapine or a triple NRTI regimen with ABC. At this meeting they reported 3 year follow-up of these subjects. Virologic and lipid data were consistent with previous reports with good viral suppression in those continued on NNRTIs versus PIs and some increased virologic failures in those on triple NRTIs, particularly in those that had evidence of NRTI resistance in the past. The additional observation of interest from this study related to some of the metabolic and physical changes which may be attributed to some of the drugs. In particular, they described an increase in fat loss syndrome, or lipoatrophy, over time which has been linked to several NRTIs, the class that was maintained on in this study. They also reported a reduction in patients complaining of the fat accumulation syndromes, such as the protuberant belly or the dorsocervical fat pad, suggesting that the PIs may have been contributing to this problem. It is important to realize that there are numerous limitations of this kind of a study; however, there is at least a suggestion that fat accumulation syndromes may be in part reversible.

Ritonavir (RTV)-Boosted Atazanavir (ATV) in Treatment Nave Subjects

ATV is a PI currently approved for treatment of antiretroviral nave subjects. Thus far there has been no available data in this patient population using RTV-boosted ATV. At this meeting the results from a trial of treatment nave subjects was reported that compared outcomes for those given once daily D4TXR with 3TC with either ATV or RTV-boosted ATV. This was a relatively small trial with 96 week planned follow-up, with the first 48 weeks presented at this meeting. The study included treatment-naive individuals and randomly assigned 95 people to ATV/RTV and 105 to ATV. The patient population was similar to that in other naive trials with a baseline HIV RNA of approximately 100,000 copies/mL and CD4 count of approximately 200 cells/uL. The primary endpoint was viral load suppression to less than 400 copies/mL. By intent-to-treat analysis 86 verses 85 were <400 copies/mL and 75 verses 70 percent at <50 copies/mL. While results showed that ATV/RTV was not inferior to ATV, there were wide confidence intervals because of the relatively small sample size. CD4 cell change was essentially the same, with an increase of 224 in the ATV group, verses 189 cells/uL in the ATV/RTV arm. There appeared to be higher rate of viral failure in those on ATV with somewhat high frequency of toxicity in those on ATV/RTV, mostly hyperbilirubinemia and some jaundice. They looked for resistance in both groups that experienced viral rebound. In the ATV/RTV group there were 3 virologic failures, one of whom had resistance and it was limited to 3TC. In the ATV-alone group there were 10 who experienced viral failure; 7 had 3TC resistance, 3 with PI resistance with the signature mutation at I50L. While this is a relatively small study, it is the first look at ATV/RTV in treatment-naive individuals, showing good efficacy, and thus far limited resistance in those taking ATV/RTV, as has been seen in select other studies with RTV-boosted PIs..

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