Durable Effects of Polylactic Acid for Facial Lipoatrophy in People with HIV

By Ronald Baker, PhD

Facial lipoatrophy (loss of fat in the face) is a constant reminder to affected HIV positive individuals that they have a devastating disease. The chief characteristics of facial lipoatrophy are sinking of the cheeks, eyes, and temples, due to loss on subcutaneous fat.

In some cases, lipoatrophy resembles AIDS-related wasting and confers an unwell appearance to many otherwise healthy people with HIV. In many cases, HIV positive people with facial lipoatrophy may feel stigmatized and severely depressed.

Facial lipoatrophy has been linked to certain antiretroviral drugs such as stavudine (d4T, Zerit). This adverse effect may lead to poor adherence to antiretroviral therapy, or refusal to start or continue treatment altogether. Poor adherence can result in drug resistance and treatment failure, while the latter can lead to HIV disease progression and further immune suppresion.

Unfortunately, the exact cause(s) of lipoatrophy remain unclear, and there is no known treatment for the condition. Switching medications may help, but studies have shown that recovery of facial fat is typically very slow.

Currently there are 2 temporarily successful interventions for facial lipoatrophy: plastic surgery or the use of fillers. One of several filler components available, polylactic acid (PLA) is called "New Fill" in Europe and "Sculptra" in the U.S. (produced by Dermik Laboratories in Berwyn, PA, a division of Aventis in trasbourg, France).

Polylactic acid is a biocompatible, biodegradable, and immunologically inert material. PLA is injected into the median-deep layer of the dermis, where the material stimulates fibroblast multiplication and collagen production.

Following an expedited review, the U.S. Food and Drug Administration (FDA) approved Sculptra to correct HIV-related facial lipoatrophy in August 2004. However, it is very difficult to get insurers to pay for this expensive treatment, which is often classified as a cosmetic procedure.

In the current open-label study, published in the March 2009 issue of HIV Medicine, HIV positive adults with lipoatrophy were randomly assigned to 4 PLA treatments administered every 2 weeks from week 0 (immediate group, n=50) or from week 24 (deferred group, n=50).

Study endpoints included facial soft tissue volume (FSTV) assessed by computed tomography, facial lipoatrophy severity, quality of life (QoL), and safety. Analyses were by intention to treat.

Results

Between weeks 24 and 48, soft tissue thickness increased modestly in injection planes, at the maxillary (mean 0.9 mm; P=0.007) and base of nasal septum levels (mean 0.4 mm; P=0.021), but not in untreated areas (P=0.79 and P=0.24).

In the immediate treatment group, PLA durability assessed at week 48 showed a mean change in FSTV of 14 cm3 (P=0.060) and increased tissue depth at the maxillary (P<0.0001), base of nasal septum (P<0.0001) and mandibular (P=0.0035) levels.

At week 48, clinicians subjectively assessed facial lipoatrophy as being reduced in the immediate treatment group 83%).

Patients in this group also said their lipoatrophy severity was reduced (91%).

The Mental Health scale score of the Short Form-36 Health Survey improved significantly in immediate participants relative to deferred participants (P=0.027).

10% of treated patients developed subcutaneous injection site nodules at 48 weeks.

Based on these results, the study authors concluded, "PLA treatment benefits were durable, with objectively assessed modest increases in facial volume and tissue thickness sustained over 48 weeks in injection planes but not in other facial areas. Improvements in some QoL domains were maintained."

National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, NSW, Australia; East Sydney Doctors, Sydney, NSW, Australia; Gold Coast Sexual Health Clinic, Miami, Queensland, Australia; Griffith University, Gold Coast, Queensland, Australia; National Association of People Living with HIV/AIDS, Sydney, NSW, Australia; St Vincent's Hospital, Sydney, NSW, Australia.

4/10/09

Reference

D Carey, D Baker, K Petoumenos K, and others (FLASH investigators). Poly-l-lactic acid for HIV-1 facial lipoatrophy: 48-week follow-up. HIV Medicine 10(3): 163-172. March 2009. (Abstract).

Other Citations

1. E Martínez, M Larrousse, D Podzamczer, and JM Gatell.
Objective amount of limb fat in HIV-infected subjects with subjective diagnosis of lipoatrophy. HIV Medicine 20(4): 257-261. April 2009.

2. DL Carey, D Baker, GD Rogers, and others. A randomized, multicenter, open-label study of poly-L-lactic acid for HIV-1 facial lipoatrophy. Journal of Acquired Immune Deficiency Syndromes 46(5): 581-9. December 15, 2007.

3. CJ Moyle GJ, S Brown, L Lysakova, and SE Barton. Long-term safety and efficacy of poly-L-lactic acid in the treatment of HIV-related facial lipoatrophy. HIV Medicine 7(3): 181-185. April 2006.

4. M Lafaurie, M Dolivo, R Porcher, and others. Treatment of facial lipoatrophy with intradermal injections of polylactic acid in HIV-infected patients. Journal of Acquired Immune Deficiency Syndromes 38(4): 393-398. April 2005.

5. MA Valantin, C Aubron-Olivier, J Ghosn, and others. Polylactic acid implants (New-Fill) to correct facial lipoatrophy in HIV-infected patients: results of the open-label study VEGA. AIDS 17(17):2471-7. November 21, 2003.