Lipoatrophy and facial wasting

17 October 2000. Related: Conference reports, Side effects, Lipodystrophy and metabolic complications, Lipodystrophy Workshop (IWADRLH) 2nd Toronto 2000.

Simon Collins, HIV i-Base

Loss of subcutaneous fat from the face – principally from the zygomato-nasal-labial triangle, cheeks (orbicular, masseter muscles) and sub-zygomatic zone – is one of the most difficult symptoms to manage in patients on otherwise virologically stable treatment. Not only is the mechanism not clearly understood, but there have been contradictory attribution to drug classes or individual drugs and other factors.

This makes altering regimens difficult, and most switching studies have reported least success in this area. Additionally, people most severely affected by facial atrophy are often those who are most treatment experienced and most reliant on their current combination.

The difficulty of these symptoms should also not be underestimated. People who have successfully stabilised progression of HIV find these changes often leave them with a cachectic appearance that can adversely affect confidence, quality of life, sexual drive and contribute to depression and diminished self-worth. As with other symptoms of lipodystrophy it can negatively impact on adherence and contribute to decisions to interrupt treatment.

Switching d4T to other nucleosides

d4T has been associated with facial atrophy in several retrospective analyses and a poster at the lipodystrophy meeting reported benefit from switching d4T to other nucleosides, without loss of virological control. Andrew Clark, from a private clinic in Cape Town reported 6 month follow-up results from switching d4T to abacavir or AZT in 11 patients (10 male, 1 female) who were naive to these drugs. [1] Minimal changes were made to other drugs, adding NNRTIs to improve virological control with one patient and also switching ddI in another with symptoms of neuropathy.

Mean known duration of HIV infection was 8.5 years (range 3-15 years) and mean duration of d4T therapy of 20.8 months (range 6-36 mo). 9/11 had viral load <50 copies. 4 patients also had symptoms of peripheral neuropathy. After six months virological suppression was maintained or improved in all patients. The patient with 36 months use of d4T (with ddI/RTV /IDV) also had a documented history of >10% weight loss with HAART (despite a CD4 increase from 115 pre-treatment to 531 cells/mm3 at study baseline). Following 6 months switched to AZT/3TC/RTV/IDV his weight stabilised and CD4 continued to rise.

Although facial wasting (and body weight) were reported as improving in 10/11 patients, this only became apparent after 6 months. Patients who also reported other body composition changes at baseline (abdominal distension, buffalo hump) did not report improvements in these symptoms.

Dr Clark noted the reluctance of many patients to change an otherwise effective therapy particularly when they felt this was associated with cosmetic concerns. Patients without alternative treatments in this clinic are provided L-acetyl carnitine. Whilst the study is small and more objective MRI scanning was not available, it may encourage clinicians to explore this option for patients with other nucleoside options.

Use of injected polylactic acid (New-Fill™) for facial lipoatrophy

Dr Patrick Armard, a plastic and maxillar surgeon, presented results from his private practice in Paris and from Hopital E. Herriot in Lyons, with Thierry Saint-Marc in the poster session from using multiple local injections of polylactic acid (PLA). This study was greatly helped by the development of sensitive subcutaneous ultrasongraphy to provide baseline and follow-up records. PLA is a ‘biocompatible, bioabsorbable and immunologically inactive’ implant that contains no animal product (unlike collagen and hyaluronic acid). There is no risk of allergic reaction and preliminary skin tests are not necessary.

There is a dual mechanism of action following PLA injections. Firstly a transient mechanical action proportional to the quantity of hydrogel volume injected. PLA then induces formation of new collagen that produces the development of a thickening of the dermal layer that is responsible for the filling action. The process of new collagen formation continues after resorption of the original PLA microparticles. PLA has previously been used to treat fine lines, cutaneous wrinkles and furrows and creases and is approved for this in Europe, but this is the first report of use in HIV-positive patients.

33 male patients (23 in Paris, 10 in Lyons) with long-term history of facial lipoatrophy (median 19 months, range 6-32mo) were given intradermal PLA injections (3cc to each cheek) every two weeks for 8 weeks. Response to treatment was assessed by ultrasonagraphy and photography on day 14 and at weeks 12, 24 and 36. The same radiologist and photographer were used for each patient.

Median previous exposure to ARV treatment was 64 ±3 months and exposure to current treatment was 9.7 ±0.7 months. 64% and 84% patients were currently on regimens containing d4T and PIs respectively. Only one third had undetectable viral load <50 copies/mm3. Most importantly, baseline facial fat loss was defined as severe in 24/33 patients (fat thickness <1mm) and moderate in the remainder (1.1-1.9mm). Mean dermal thickness at baseline was 3.2±0.8mm (1-5.8mm) and mean fat thickness was 0.6±0.8mm (0-3mm).

Preliminary results are summarised in Table 1 below.

Table 1

Although only low numbers have reached 24 and 36 week endpoints, the photographic records included in the poster looked both more accurate and more impressive than usually included in lipodystrophy studies. This included apparent reversal of the distinctive sunken triangle below the check bones at the front of the face which is increasingly prevalent especially amongst men who have been on treatment for several years – referred to in one article with customary US directness as the ‘Dachau Dimple’!

A larger study following the same protocol (50 patients) has already been started at the Pitié-Salpétrière Hospital in Paris under Professor Christine Katlama and results from this are expected by June 2001. A similar initiative in the UK is unlikely to have difficulty with recruitment.

Poly-L-lactic acid (L-PLA) is produced by Purac Biochem with brand-name New-Fill

The cost (for the product only) is approximately 5500 FF per person for a complete treatment.

References:

1. Clark, A – Improvement in Facial Atrophy after Substitution of Stavudine. Abstract P85. 2nd Intl Workshop on Adverse Drug Interactions and Lipodystrophy, Toronto, Sep 2000.
2. Amard, P et al – The Effects of Polylactic Acid (PLA) (New-Fill¨) as Therapy for Lipoatrophy of the Face. Abstract P94. 2nd Intl Workshop on Adverse Drug Interactions and Lipodystrophy, Toronto, Sep 2000.