This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The hypothesis of the proposed study is that thymidine analogues more so than non-thymidine analogues cause lipoatrophy and that removal of these drugs from an antiretroviral regimen in subjects with defined lipoatrophy will reverse this process. A5110 is a pilot trial of two interventions that may reverse treatment-related lipoatrophy. The first intervention involves removing the thymidine analogue component of the treatment regimen. In this situation, abacavir (ABC) is used to replace the thymidine analogue. In the second intervention, all nucleoside analogues are removed and therapy is changed to a protease inhibitor/non-nucleoside reverse transcriptase inhibitor (PI/NNRTI) regimen. Comparisons are made to the baseline values of subcutaneous fat cross-sectional area measured by mid-thigh and abdominal computed tomography (CT). Each intervention strategy will have a prerandomized but deferred treatment arm that initiates therapy after 28 weeks to evaluate the natural history of change in lipoatrophy over time. If both interventions are effective, a larger study will be needed in order to compare interventions directly unless a difference of 43% is observed between the intervention arms. The choice of therapy for the second intervention, lopinavir/ritonavir (LPV/r) plus nevirapine (NVP), was chosen because of the expected superior potency of the regimen over other potential combinations of these two classes, and assumes that PIs and NNRTIs have little or no impact on lipoatrophy. Multiple 'switch' studies have shown that the strategy of switching one of the components of a potent antiretroviral regimen within the same class of antivirals or to a different class, is safe and not associated with a significant increase in virologic relapse. This project is AIDS related.
Showing the most recent 10 out of 470 publications
