[P-21] The relation between duration of zidovudine (ZDV) use and limb fat content is dependent on whether used in combination with a boosted protease inhibitor (PI) or with a non-nucleoside reverse transcriptase inhibitor (NNRTI)

10th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV

6-8 November 2008, London, UK

THE RELATION BETWEEN DURATION OF ZIDOVUDINE (ZDV) USE AND LIMB FAT CONTENT IS DEPENDENT ON WHETHER USED IN COMBINATION WITH A BOOSTED PROTEASE INHIBITOR (PI) OR WITH A NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR (NNRTI)

ANTIVIRAL THERAPY 2008; 13(Suppl. 4):A37 (abstract no. P-21)

SME Vrouenraets_1,2, E Fernandez Garcia², M Huber³, K Brinkman⁴, G Moyle⁵, P Domingo⁶, PE Tarr⁷, D Podzamczer⁸, M Ristola⁹, JM Gatell¹⁰, JM Livrozet¹¹, FWNM Wit^1,2, H Furrer¹² and P Reiss^1,2 for the PREPARE Study Group
¹Academic Medical Center, Amsterdam, the Netherlands; ²IATEC, Amsterdam, the Netherlands; ³Universitätsspital Zürich, Zürich, Switzerland; ⁴OLVG, Amsterdam, the Netherlands; ⁵Chelsea and Westminster Hospital, London, UK; ⁶Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; ⁷University Hospital, Lausanne, Switzerland; ⁸Hospital Bellvitge, Barcelona, Spain; ⁹Helsinki University Central Hospital, Helsinki, Finland; ¹⁰Hospital Clínico de Barcelona, Barcelona, Spain; ¹¹Hopital Edouard Herriot, Lyon, France; ¹²University Hospital and University of Bern, Bern, Switzerland

OBJECTIVES: Recent results from a randomized trial in treatment-naïve patients have suggested dual nucleoside reverse transcriptase inhibitor (NRTI) treatment plus lopinavir/r to be associated with less limb fat loss than when used with the non-NRTI (NNRTI) efavirenz. We assessed body fat distribution in relation to duration of zidovudine use and in conjunction with either a protease inhibitor (PI) or NNRTI, using baseline body composition data from a randomized multicentre multinational trial that compares continued suppressive first-line antiretroviral therapy (ART) with zidovudine/lamivudine with switching to tenofovir/emtricitabine, both plus either a NNRTI or a PI (PREPARE).

METHODS: Baseline data, including centrally read whole body dual energy X-ray absorptiometry- and single slice abdominal CT-scans (at level L4), were used for this analysis. Relations between prior ART use and body composition parameters were assessed using linear regression models corrected for gender, ethnicity and body mass index (BMI).

RESULTS: Of 135 patients, 117 were men, mean (sd) age 45.6 (10.0) years and body mass index was BMI 24.3 (3.2) kg/m². Mean duration of ART was 6.2 (2.6) years and baseline CD4 count was 557 (271) cells/mm³. Plasma HIV-1 RNA <50 copies/ml was recorded in 132 patients (97.8%). At present, 101 patients, 21 of whom had used PIs previously, used an NNRTI-containing regimen (59 efavirenz and 42 nevirapine). At present, 34 patients, 8 of whom had used NNRTIs previously, were on a PI-containing regimen, mostly lopinavir/r (n=18) or atazanavir(/r) (n=9). Limb fat amount was lower with longer zidovudine exposure, 200 g less per additional year of ART (P=0.017). Comparing the third drugs, PI-treated patients had 408 g less limb fat per additional year of ART (P=0.008), compared with 96 g less per year in those on NNRTI (P=0.266). In those on NNRTI, 194 g (P=0.154) and 28 g (P=0.844) less limb fat per year was seen for efavirenz and nevirapine, respectively. A sensitivity analysis (PI n=26 and NNRTI n=80) limited to patients who consistently had either used PI, efavirenz or nevirapine found similar results (540, 108, and 83 g less limb fat per additional year of ART, respectively) with a significant difference between PI and NNRTI as a class (P=0.021). Subcutaneous adipose tissue was also significantly related to ART exposure (P=0.007) and most pronounced in PI- treated patients (12.2 cm² less per year of ART compared with -2.2 cm² in NNRTI-treated). A trend towards more (+12.2 cm², P=0.060) visceral adipose tissue per year of ART was seen in PI-treated patients (sensitivity analysis +13.6 cm², P=0.030) but not in NNRTI-treated patients (+1.5cm², P=0.640).

CONCLUSIONS: Longer duration of zidovudine exposure increases the likelihood of subcutaneous fat loss and possibly visceral adipose tissue gain. This association is most pronounced when combined with a PI and less with either efavirenz or nevirapine.

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2008-11-06
P-21

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