Antiretoviral therapy and the lipodystrophy syndrome, part 2: concepts in aetiopathogenesis.

Centre for Clinical Immunology and Biomedical Statistics, Royal Perth Hospital and Murdoch University, Western Australia.
Antiviral therapy (Impact Factor: 3.14). 10/2001; 6(3):145-60.
Source: PubMed

ABSTRACT Clinical research has indicated that the use of nucleoside reverse transcriptase inhibitor (NRTI) and HIV protease inhibitor (PI) therapy is associated with a risk of long-term toxicity syndromes, and that the aetiopathogenesis of these adverse effects is independent of the antiretroviral effects of these drugs. In relation to the lipodystrophy syndrome, it appears that the most powerful determinant of subcutaneous fat wasting is an interaction between these two drug classes. In this review, possible mechanisms underlying the contributions of both PI and NRTI drugs are reviewed, with an emphasis on their effects on adipose tissue. On this basis, an 'adipocentric', or minimal model of the syndrome is developed, in which divergent effects at the adipocyte of NRTIs (mitochondrial toxicity) and PIs (insulin resistance and impaired adipocyte maturation) interact to produce a phenotype that is consistent with clinical observations.


Available from: Simon Mallal, May 26, 2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: It is estimated that about 2.5 million people are living with HIV infection in India. Although antiretroviral drugs have been able to reduce the mortality, these drugs have serious side effects one of which is lipodystrophy syndrome. Most of the drugs used in HAART viz, protease inhibitors, stavudine and nevirapine are associated with lipodystrophy. Hence we conducted this study to assess the prevalence of lipodystrophy in HIV infected children on HAART and its associated risk factors. Materials and methods: A cross sectional study was conducted on 80 HIV infected children aged 2-18 years of age who were on stavudine based HAART for >= 2 years. These children were assessed for presence of lipodystrophy, its metabolic complications and associated risk factors. Results: Lipodystrophy was observed in 33.7% of children with lipoatrophy being the commonest subtype followed by lipohypertrophy. Older age, increased duration of treatment and dyslipidaemia were found to be associated in patients with lipodystrophy than those without. On further multivariate analysis of independent risk factors only increased duration of treatment was significantly associated with lipodystrophy. No association was found with insulin resistance. Conclusion: We observed that lipodystrophy is a common finding in HIV patients treated with HAART for long duration.
    African Health Sciences 06/2014; 14(2):408-13. DOI:10.4314/ahs.v14i2.17 · 0.66 Impact Factor
  • Drug-Induced Mitochondrial Dysfunction, 01/2008: pages 473 - 491; , ISBN: 9780470372531
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Highly active antiretroviral therapy regimens (usually three-drug combinations) have shown undisputable efficacy in the reduction of the morbidity and mortality of HIV-infected patients. However, these regimens are only virustatic, which means that, in order to suppress viral replication, treatments should be maintained for life, without any additional benefit over time once immune restauration has been obtained. Besides, there is a debate on when to start therapy because profound immunodepression may not be totally reversible, recognizing that earlier treatment means longer drug exposure. On the other hand, the long-term toxicity of these drugs has generated new problems such as the appearance of the lipodystrophy syndrome and the increase of cardiovascular morbidity observed in patients treated for several years, particularly with HIV protease inhibitor-containing regimens. Therefore, new drugs are needed, not only for patients experimenting virological failure but also for successfully treated patients, in order to reduce toxicity, and these new drugs must now be screened for metabolic disturbances and adipocyte toxicity as well as for antiretroviral activity. Alternatively, new strategies, such as specific or non-specific immune-based therapy, reinforcing drug efficacy or allowing treatment interruptions, must be developed.
    Current Medicinal Chemistry - Anti-Infective Agents 01/2005; 4:29-36. DOI:10.2174/1568012052931197