ritonavir and Atrophy

Discontinuation of thymidine nucleoside reverse transcriptase inhibitors (tNRTIs) is the only proven strategy for improving lipoatrophy. It is unclear whether switching to NRTI-sparing or to non-thymidine NRTI-containing therapy has differential effects on body fat recovery.. This was a 96 week, open-label, randomized study in suppressed patients with moderate/severe lipoatrophy and no prior virological failure while receiving a protease inhibitor and who had their triple NRTI regimen (zidovudine/lamivudine/abacavir) switched to lopinavir/ritonavir plus abacavir/lamivudine for a 1 month run-in period and then randomized to lopinavir/ritonavir plus abacavir/lamivudine versus lopinavir/ritonavir monotherapy. The KRETA trial is registered with ClinicalTrials.gov (number NCT00865007).. Of 95 patients included, 88 were randomized to lopinavir/ritonavir plus abacavir/lamivudine (n = 44) or lopinavir/ritonavir monotherapy (n = 44). Median (IQR) baseline limb fat was 2.5 (1.6-3.7) kg in the lopinavir/ritonavir plus abacavir/lamivudine group and 2.5 (2.0-5.4) kg in the lopinavir/ritonavir monotherapy group. Six patients in the triple therapy group and 13 in the monotherapy group had discontinued study drugs by week 96. Although there were limb fat gains in each group at weeks 48/96 (+324/+358 g in lopinavir/ritonavir plus abacavir/lamivudine, P = 0.09/0.07, versus +215/+416 g in the lopinavir/ritonavir monotherapy group, P = 0.28/0.16), differences between groups were not significant [difference +109 g (95% CI -442, +660)/-57 g (95% CI -740, +625)].. In lipoatrophic patients treated with zidovudine/lamivudine/abacavir, switching to lopinavir/ritonavir monotherapy had no additional benefit in limb fat recovery relative to switching to lopinavir/ritonavir with abacavir/lamivudine. These data suggest that non-thymidine nucleosides such as abacavir/lamivudine are not an obstacle to limb fat recovery.

Topics: Absorptiometry, Photon; Adipose Tissue; Adult; Antiretroviral Therapy, Highly Active; Atrophy; Body Composition; Chemistry, Pharmaceutical; Dideoxynucleosides; Female; HIV Infections; HIV Protease Inhibitors; Humans; Intention to Treat Analysis; Lamivudine; Lipids; Lipodystrophy; Lopinavir; Male; Middle Aged; Reverse Transcriptase Inhibitors; Ritonavir; Treatment Failure

No randomized study has prospectively followed subcutaneous adipose tissue mitochondrial DNA (mtDNA) changes when starting thymidine nucleoside reverse transcriptase inhibitors (tNRTIs).. The Metabolic Effects of DIfferent CLasses of AntiretroviralS study randomized HIV-positive, treatment-naive male participants to start lopinavir/ritonavir (LPVr) with either zidovudine/lamivudine (ZDV/3TC) or nevirapine (NVP).. Regional body fat was assessed by dual energy x-ray absorptiometry and abdominal computed tomography at months 0, 3, 12, 24 and 36. In a molecular substudy, subcutaneous adipose tissue (SAT) biopsies were taken, with mtDNA quantified by quantitative PCR. Data were analyzed using repeated measures linear regression analyses.. Of 50 participants recruited (23 to LPVr/ZDV/3TC), 48 started therapy, and 37 participants (19 on LPVr/ZDV/3TC) enrolled in the substudy. At 36 months, the LPVr/ZDV/3TC group had significantly lower limb fat [6.4 kg (0.26) versus 7.3 kg (0.31), P = 0.017] and a trend toward lower abdominal SAT compared to the LPVr/NVP group [131 cm (6.86) versus 146 cm (6.33), P = 0.097]. Over 36 months, mtDNA declined in the LPVr/ZDV/3TC group [mtDNA region 1: -190 (95) copies/cell, P = 0.053, region 2: -269 (106) copies/cell, P = 0.016] but not within the LPVr/NVP group [region 1: +28 (99) copies/cell, P = 0.78, region 2: +51 (111) copies/cell, P = 0.65, between-group difference P < 0.01 for both measurements]. mtDNA was significantly lower in the LPVr/ZDV/3TC group at 36 months.. This is the first randomized study to prospectively demonstrate reductions in SAT mtDNA in patients initiating ZDV/3TC-containing antiretroviral therapy (ART) but not in those initiating nucleoside reverse transcriptase inhibitor-sparing ART containing NVP and protease inhibitor. That reductions in SAT mtDNA were also accompanied by lower limb fat suggests that use of ART not containing ZDV/3TC may help prevent development of peripheral lipoatrophy.

Topics: Absorptiometry, Photon; Acquired Immunodeficiency Syndrome; Adolescent; Adult; Aged; Anti-HIV Agents; Atrophy; CD4 Lymphocyte Count; DNA, Mitochondrial; Drug Combinations; Drug Therapy, Combination; HIV Seropositivity; HIV-1; HIV-Associated Lipodystrophy Syndrome; Humans; Lamivudine; Lopinavir; Male; Middle Aged; Nevirapine; Prospective Studies; Reverse Transcriptase Inhibitors; Ritonavir; RNA, Viral; Subcutaneous Fat; Treatment Outcome; Young Adult; Zidovudine

Topics: Atrophy; Fluorescein Angiography; HIV Protease Inhibitors; Humans; Retina; Retinal Diseases; Retinal Pigment Epithelium; Ritonavir; Tomography, Optical Coherence