[19] PROTEASE INHIBITORS AND NUCLEOSIDE ANALOGUE REVERSE TRANSCRIPTASE INHIBITORS INTERACT TO CAUSE SUBCUTANEOUS FAT WASTING IN PATIENTS WITH HIV INFECTION

1st International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV

26–28 June 1999 - San Diego, CA, USA

PROTEASE INHIBITORS AND NUCLEOSIDE ANALOGUE REVERSE TRANSCRIPTASE INHIBITORS INTERACT TO CAUSE SUBCUTANEOUS FAT WASTING IN PATIENTS WITH HIV INFECTION

Antiviral Therapy 1999; 4(Suppl. 2):42 (abstract no. 19)

S Mallal¹, M John¹, C Moore^1,2, I James² and E Mckinnon²
¹Department of Clinical Immunology, Royal Perth Hospital, Perth; and ²Mathematics Programme, Murdoch University, Murdoch, Australia

BACKGROUND: Progressive subcutaneous fat wasting, dyslipidaemia and insulin resistance have been described in HIV-infected patients on highly active antiretroviral therapy (HAART), and have been solely attributed to the long-term toxicity of HIV PIs, which are one component of HAART. The more recent observations of fat wasting developing in patients who have never had PIs implicate an independent effect of nucleoside analogue reverse transcriptase inhibitor (NRTI) therapy.

OBJECTIVES: To examine the relative contribution of individual NRTIs and PIs to subcutaneous fat wasting in patients treated with HAART

DESIGN: We examined 271 participants of the Western Australian HIV cohort study for fat wasting using standardized clinical criteria. The time to onset of clinically apparent fat wasting in patients receiving different antiretroviral regimens was compared. The percentage body fat composition as measured by dual energy x-ray absorptiometry (DEXA) in 156 patients was also compared.

RESULTS: Fat wasting was observed in 103 of 203 (51%) PI-treated patients and in only 9 of 66 (14%) PI-naïve patients (P<0.001). In all patients, the age adjusted risk of developing clinically apparent fat wasting was increased by the use of PI at any time (P=0.003, OR=3.8, multivariate logistic regression), longer cumulative time on stavudine (P=0.006, OR=1.051 per month) and longer cumulative time on zidovudine (P=0.0008, OR=1.025 per month). In the 233 patients treated with HAART, age (P=0.0001, RR=1.057 per year), race (P=0.025, RR=3.8 for whites), longer duration of dual NRTI therapy prior to commencement of HAART (P=0.013, RR=1.019 per month) and increased cumulative time on stavudine containing HAART compared with time on zidovudine (P=0.0001, RR=1.088 per month) were associated with a shorter time to onset of fat wasting. The results of DEXA scanning supported the clinical outcome data. Longer cumulative times on NRTI monotherapy, NRTI dual therapy and HAART containing stavudine were associated with lower percentage subcutaneous fat in the legs (P=0.018, 0.001 and 0.001 respectively, multivariate linear regression). Sequential DEXA scanning showed an average 15% (95% CI 9-21%) reduction in leg fat for each year on HAART.

CONCLUSIONS: The wasting of fat from the subcutaneous compartments of the face, limbs and central abdomen occurring in HIV-infected patients cannot be explained by PIs alone. NRTIs appear to cause slowly progressive fat loss, which is accelerated by the addition of protease inhibitor therapy. HAART regimens containing stavudine cause faster fat loss and an earlier onset of clinically apparent wasting compared to those containing zidovudine.

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Copyright © 1999 - International Medical Press Ltd. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Medical Editor, International Medical Press, 36 St Mary-at-Hill, London EC3R 8DU, United Kingdom.