Polylactic acid (New-gill) repairs facial wasting and improves quality of life
1 December 2003. Related: Lipodystrophy and metabolic complications.
Simon Collins, HIV i-Base
Early reports from using New-fill to safely and successfully repair facial lipoatrophy provided hope for many patients, given that the procedure was inexpensive in the context of overall HIV therapy, that it indicated few safety concerns and most importantly, when given by an HIV-experienced practitioner, produced successful and natural-looking results for many patients.
Facial lipoatrophy is the loss of facial fat especially in the buccal region that results in a progressively emaciated appearance and which is the cause of significant patient distress and reduced quality of life [1].
Concern about lipoatrophy is a reason that many patients give for delaying use of treatment, and the most recent research from Nolan et al suggests that the underlying mechanism for altered adipocyte differentiation and increased apoptosis is linked to nucleoside-related mitochondrial toxicity [2].
Results from using New-Fill were first presented at the 2nd Lipodystrophy Workshop in 2000, and have since been presented at most large meetings since then, but access to New-Fill has been limited to a restricted number of patients through National Health Service programmes or through private practice [3, 4].
It is therefore important that one of the earliest and largest studies has now been published in the influential peer-reviewed journal AIDS [5]. This together with inclusion of New-Fill as an appropriate treatment for lipoatrophy in the UK Treatment guidelines should broaden access further [6].
In the VEGA study, 50 patients from Hôpital Pitié-Salpêtrière, Paris, with severe facial lipoatrophy who had been receiving antiretroviral treatment for >3 years (median 8.9 years) and had viral load suppression <5000 copies/mL, were treated in an open label single arm pilot study. At baseline, median facial fat thickness measured by ultrasonography and colour Doppler evaluation was zero (range 0.0-2.1mm).
This careful and objective measurement of changes in the dermal, epidermal and fat thickness by the same trained radiography for all patients is an important aspect of the study and was supported by photography. Patients were evaluated at weeks six, 24, 72 and 96 and quality of life (QoL) measured at screening, at month three, and subsequently every six months out to two years.
Patients received a set of injections (one vial of New-fill, 0.15g dry powder reconstituted with 3-4ml water) at baseline and every two weeks. A fifth injection could be given if total cutaneous thickness (TCT) was <8mm after the fourth injection. Each treatment involved up to 20 deep injections into and around the deep dermis of each cheek. Lidocaine was injected locally and thorough massaging of the treated area is essential to ensure better distribution of the solution.
Three, four and five sets of injections were provided to four, 26 and 20 patients respectively. Mean (and range) TCT increases in millimetres from baseline were +5.1 (2.2-8.6), +6.4 (3.1-9.1), +7.2 (4.2-9.6), +7.2 (3.5-9.6) and +6.8 (3.9-10.1) at weeks six, 24, 48. 72 and 96 respectively, and indicated a sustained effect over 18 months after the last injection, and also at least some level of response among all patients. Just over 40% of patients achieved primary endpoint of the study with TCT greater than an arbitrary 10mm at week 24, which was maintained out to week 96 (p<0.001 at both time points).
Median change in QoL, obtained from 44 patients, progressively improved from baseline to +8.0 (range, -2.9 – +10.0) at week 48 and was the secondary endpoint of the study (p=0.021), although this dropped to +0.4 at week 96 and lost statistical significance.
Minimal and localised oedema at injection site was seen in most patients and resolved within 24-48 hours. Fifteen patients developed minimal ecchymosis, which resolved spontaneously within 2-3 days. 22 patients reported palpable (but non-visible) subcutaneous micronodules that resolved in six patients by week 96. [Note: Further clinical experience suggests that this risk is minimised by intense post-injection massage, and that this is essential element of care].
The authors comment on the importance of these results in the absence of other effective strategies to manage facial lipoatrophy and say that the data should provide health providers and payers with sufficient efficacy and safety data to consider reimbursement.
It is also notable that the journal carried an editorial comment that highlighted the importance of New-fill being administered by a practitioner specially trained in treating HIV-associated lipoatrophy, and concluded that “at last we have something with clear results to offer to our patients”.
Comment
Although the process for providing New-fill within the NHS has been slow and protracted, several major centres are now providing this treatment at least for some patients, and commissioner funding has been forthcoming. In an overview at the Autumn BHIVA conference, Dr Simon Barton estimated that several hundred people have probably been treated on the NHS and a similar number in private practice.
Of note, Brighton provided treatment to more than 50 patients last year and the long-expected programme at the Chelsea and Westminster Hospital in London has started evaluation and treatment of patients most affected.
At least two commissioning documents have already been produced that may be useful for clinicians obtaining this treatment for their patients [7, 8].
References:
- Patient perspective. Presentation at HIV i-Base meeting on access to New-Fill, January 2002.
http://www.i-base.info/i-basemeetings/lipo/patient.html - 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. Programme and abstracts from the 5th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV, 8-11 July 2003, Paris Abstract 18.
- Lipoatrophy and Facial Wasting: Report from 2nd International Workshop on Adverse Drug Reactions and Lipodystrophy. Toronto, Canada, September 13-15, 2000. HIV Treatment Bulletin Vol1No7 October 2000.
https://i-base.info/htb/3945 - Approaches to treatment of lipodystrophy. HIV Treatment Bulletin Vol 4 No 3 April 2003.
https://i-base.info/htb/10986 - Valantin MA, Aubron-Olivier C, Ghosn J et al. Polylactic acid implants (New-Fill) to correct facial lipoatrophy in HIV-infected patients: results of the open-label study VEGA. AIDS 2003, 17:2471–2477.
- Pozniak A, Gazzard B et al for BHIVA Writing Group. British HIV Association (BHIVA) guidelines for the treatment of HIV-infected adults with antiretroviral therapy. July 2003. Published online.
http://www.bhiva.org - West Midlands Specialist Services Agency. New-Fill for the treatment of Facial Lipoatrophy in HIV positive patients, June 2003.
http://www.cswwm.org.uk/support.htm - North West London Sector. New-Fill Treatment Protocol For Facial Use. January 2003.