Treatment interruption: a real choice

At the end of the last day of the Workshop an important discussion provided a controversial focus concerning clinical management of lipodystrophy.

A presentation from Emmanuel Trenado of results from a prospective cohort study of 725 HIV patients, almost 600 of whom had answered a questionnaire distributed by the French community organisation AIDES, and of the 80% on treatment almost 40% said that on their ‘stable’ combination they experienced mild to moderate side effects. [27] Sexual dysfunction, sleep disorders, lipodystrophy and fatigue were each reported in 17-20% of the questionnaires.

Perhaps unsurprisingly, people reporting side effects were three times more likely to be interested in taking a treatment interruption, but 10% of the cohort were already taking a break from treatment and half of these people were doing this without consulting their doctors.

Perception of body shape changes in a multivariate analysis from the APROCO cohort was also a significant predictor of adherence failure at month 20 in patients who had previously reported excellent adherence (the only other two factors being daily alcohol use and age).

A summary of management of lipodystrophy by Christine Katlama excluded stopping treatment as an option that clinicians should recommend (for the treatment of metabolic alterations), but this is clearly an approach taken by people in real life. Whatever the exact mechanisms for the body shape changes, HIV treatment is now recognised as a significant contributory factor – and a wealth of studies at every lipodystrophy workshop attests to direct effects on mouse, rat or human cells other than purely targeting of HIV.

Risk factors from a treatment interruption in numerous studies include previous CD4 nadir and history of opportunistic infections, and also perhaps severity of original seroconversion symptoms.

Martinez and colleagues from Barcelona reported effects of a treatment interruption in 10/15 patients with symptoms of lipodystrophy and 5/8 without lipodystrophy. After one year there was a trend to fat gain and fat-free mass loss with minimal change in bone mineral density. Patients who interrupted treatment both with and without symptoms of lipodystrophy had greater increases in weight, BMI, total fat and spine BMD and lower decreases in fat-free mass compared to patients who continued HAART. [28]

While this is not a straightforward option for many patients, that it is always an option that some may choose highlights the real difficulties and urgency of discovering alternative treatment and management options.

References:

Unless otherwise stated, all abstracts refer to the programme and abstracts from the 5th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV, 8-11 July 2003, Paris and are published in Antiviral Therapy Volume 8 issue 4.

  1. Capeau J, Caron M, Auclair M et al – Effects of NRTI on differentiation, response to insulin and apoptosis in cultured adipocytes. 2nd IAS Conference on HIV Pathogenesis and Treatment, 13–16 July, Paris. Abstract 206.

  2. Yamauchi T - The roles and mechanisms of adipocytokines in insulin resistance. Abstract P3.

  3. Khatami H, Mulligan K, Lo JC et al – Role of adipocytokines and body fat distribution in insulin resistance in HIV infection. Abstract 44

  4. Frayn K - Adipose tissue and insulin resistance. Abstract P2.

  5. Deveaud C, Beauvoit B, Rogoulet M – Effects of the treatment by nucleoside reverse transcriptase inhibitors on mitochondrial function of superficial and deep adipose tissues of rats. Abstract 50.

  6. Maisonneuve C, Begriche K - Effects of AZT and d4T on ketone bodies and lipids in mice: possible role of beta-aminoisobutyric acid, a catabolite of thymine. Abstract 20.

  7. Flint OP, Mulvey R, Elosua C et al – The effect of tenofovir, zidovudine and stavudine on adipocyte mitochondrial DNA, viability and lipid metabolism. Abstract 65.

  8. Caron M, Auclair M, Kornprobst M et al - Effects of NRTI on differentiation, response to insulin and apoptosis in cultured adipocytes. Abstract 10.

  9. Capeau J, Bastard JP, Cervera P et al - Increased IL-6 and TNF expression is related to increased apoptosis and decreased differentiation in adipose tissue from patients with HIV-related lipoatrophy. Abstract 9.

  10. Nolan D, Hammond E, McKinnon E et al - Subcutaneous fat tissue mitochondrial DNA depletion and adipose toxicity are strongly associated with nucleoside reverse transcriptase inhibitor (NRTI) therapy in HIV-infected patients. Abstract 18.

  11. Lopez S, Miro O, Martinez E et al – Does HIV infection itself have any effect on mitochondrial DNA content? Abstract 54.

  12. Tebas P, Mondy K, De Ronde A et al – Effects of different antiretroviral treatments on mitochondrial DNA levels in PBMCs of HIV-infected patients. Abstract 60.

  13. Shahmanesh M, Das S, Stolinski M et al - Effects of HIV infection, antiviral treatment and body fat changes on VLDL-apolipoprotein-B metabolism. Abstract 3.

  14. Mercie P, Thiebaut R et al - Carotid intima-media thickness is moderately increased over time in HIV-1-infected patients. Abstract 2.

  15. Hsue P, Lo J, Franklin A et al – Predictors of atherosclerosis and atherosclerotic progression in patients with HIV: the role of traditional and immunological risk factors. Abstract 35

  16. Grinspoon S, Dolan SE, Huang JS et al – Reduced bone mineral density in HIV-infected women. Abstract 24.

  17. Hadigan C, Yawetz S, Thomas A et al - A randomised, double-blind, placebo-controlled study of rosiglitazone for patients with HIV lipodystrophy. Abstract 12.

  18. Oette M, Gobels K, Kurowski M et al – Rosiglitazone treatment of HIV-associated lipodystrophy syndrome: impact on the bioavailability of antiviral compounds. Abstract115.

  19. Driscoll S, Meininger G, Lareau M et al - Effects of exercise training and metformin on body composition and cardiovascular indices in HIV-infected patients. Abstract 4.

  20. Carr A, Martin A, Ringland C et al - Long term changes in lipodystrophy after switching from thymidine nucleoside analogues to abacavir. Abstract 16.

  21. Raghavan S, Shlay JC et al - Rates of change in body composition among antiretroviral-naïve HIV-infected patients randomised to a didanosine/stavudine versus abacavir/lamivudine containing regimen in the Flexible Initial Retrovirus Suppressive Therapies (FIRST) study (CPCRA 058). Abstract 13.

  22. Frize G, Hughes A, Scullard G et al – Attitudes and perceptions of patients with facial lipoatrophy before and after intervention using polylactic acid. Abstract 110.

  23. Guaraldi G, De Fazio D, Orlando G et al - Fat accumulation of the cheeks after autologous fat transfer for treating facial wasting in HIV-related lipodystrophy. Abstract 81.

  24. Walker U, Koch E, Venhoff N et al - Uridine prevents and treats mtDNA depletion by NRTI pyrimidine analogues and fully restores mitochondrial function. Abstract 19.

  25. Garcia M, Martinez E, Domingo P et al – Breast enlargement in male HIV-infected patients. Abstract 82.

  26. Allin M, Reeves I, Everal I et al – Frequency of serious psychiatric adverse events with efavirenz. Abstract 129.

  27. Trenado E - Lipodystrophic body changes and quality of life. Clinical management workshop.

  28. Martinez E, Milenkovic A, Vidal S et al – Impact of structured treatment interruption on body composition of chronically infected patients: preliminary one year results. Abstract 88.

HIV Treatment Bulletin Vol 4 No7 August / September 2003