HIV Treatment Bulletin - Vol. 6, No. 1, December 2004 / January 2005
Simon Collins, HIV i-Base

Although several posters focused on practical and corrective treatments for lipoatrophy, only a few studies provided new information.

The benefit and efficacy of New-fill (Poly-L-Lactic Acid, PLA, Sculptra) has already covered extensively in HTB in reports from previous years meetings. None of the studies at this year’s Workshop provided longer-term efficacy data or additional safety concerns to those already reported from those earlier studies.

Given that New-fill has been available for some years in Europe, and received FDA marketing approval in August this year, the most pressing issue largely remains access and reimbursement. Psychological well-being and improved quality of life have consistently improved in all studies.

In the UK, New-fill is increasingly available in some clinics, though there is a back-log for screening and treatment in the London-wide access funded by the pan-London consortium.

New aspects addressed at the meeting, included data on alternative treatments to New-Fill, and treatment of non-facial lipoatrophy - although thee were only extremely limited data on each of these.

Polyalkylimide (Bio-Alcamid, Polymekon)

The action of New-Fill is to generate natural collagen growth to fill the gap left by the lost fat, with the active ingredient being quickly absorbed, and the resulting replacement collagen lasting upwards of two years.

Bio-Alcamid is an injectable biopolymer (pH 6.8-7.2) that is used as a filler, that is expected to produce permanent results, and this may have benefits for some patients. The supporting information says that once injected it becomes coated by a ‘thin collagen capsule’ that transforms it into an endogenous prosthesis. It is used in Europe mainly in private clinics for HIV-related lipoatrophy (including in the UK) and is a CE0123-marked product (ie passed certain safety standards), but does not have FDA approval. [1]

Results from private clinics using Bio-Alcamid for HIV-related lipoatrophy have been reposrted at prvious lipodystrophy Workshops, but these studies have so far not been as closely monitored as the New-Fill studies. In addition to a longer effect, other interesting claims for Bio-Alcamid is that it can be used in higher volume applications (0.5-20cc), is suitable for non-facial lipoatrophy, and that is can be removed in case of ‘over-filling’.

At the Workshop, Dr. Luis Casavantes presented a poster on 100 patients treated with Bio-Alcamid at a private clinic in Tijuana. Mexico [2].

Photographs are often the clearest way to judge how effective and natural the results are after treatment. The examples used in the poster at this meeting, though not reproducible in HTB, showed ten before and after shots of eight men and two women who started with severe facial lipoatrophy and achieved impressive and very natural final results after 2-3 treatments.

Treatment was reported as well tolerated and the facial deficits were “fully and permanently restored” after two to four sessions in 100% of patients. A sonogram after 4 months in one patients showed positioning of a gluteal implant and a biopsy sample after 8 months in another was used to showed minor acute inflammation but no signs of chronic inflammation or granulomas. Recuperation time was reported as taking 0-3 days in all patients.

Finally, a set of photographs was included of buttock treatment, implanted in four sites in each buttock (total 425cc Bio-Alcamid), that showed substantial improvements a 53 year old male patient.

The removable procedure for Bio-Alcamid, shown in the poster, is by puncturing the skin with needle and squeezing out unwanted filler. This has not been varified in clinical studies, and annecdotally, non-surgical removal may not always be so straight-forward.

Other approaches

Other approaches reported at the meeting included:

• Polymethylmethacrylate (PMMA, Artecoll), a compound that is neither EMEA nor FDA approved but which has been used in a clinic in Rio de Jenero. [3] The poster presented results from 10 men and 12 women with lipoatrophy of the buttocks, legs, arms and pubis. Objective measurements (ultrasound, calipers etc) were not presented and photographic examples looked less successful than Bio-Alcamid, with most ‘before’ photographs showing far milder lipoatrophy.
  Investigator claims and patient self-reports, included good efficacy with light to moderate pain lasting for two to three days, but until safety data are available for this compound and studies conducted in a more rigorous way, the inclusion in this HTB report is intended mainly to indicate the degree to which many compounds are already being used off-label and unregulated.


• Autologous Fat Transfer surgery (AFT) – where subcutaneous fat is collected usually from the abdominal are and transferred to the hollows in the face. This is a standard corrective surgical procedure that is generally more traumatic with greater recovery time. The limitations, apart from higher costs, include low availability of fat to harvest from many people who have facial lipoatropy. It would be interesting to know whether the transported fat allows permanent generation of new and appropriate fat cells. One important caution, also reported at last years meeting, is to not use fat associated with fat accumulation (ie brown fat taken from dorso-cervical pads. In four patients the transplanted fat has grown back at the same time as the shoulder fat returned, creating swollen cheeks that have not been re-correctable with liposuction. [4, 5]


• Polyacrylamide (PCA, brand names include Aquamid, Argiform, DermaLive) – which appears to have several disadvantages compared to polyalkylamide discussed above (ie has lower elasticity and cohesiveness, requires buffer to counter acidy, is less heat stable and less flexibility for removal)
  
  The Italian researchers that have reported autologous fat transfer studies at this and previous Workshops, also provided data from a prospective, partially randomised study comparing New-Fill, AFT and polyacrylamide (patients who had insufficient fat to harvest were not included in the AFT randomization) in 59 patients at 24 weeks. [6]
  
  Ultrasound (increase of 3-3.5mm in buccal thickness at 24 weeks) and photography provided objective measurement that were comparable in the three groups. Patient satisfaction showed no significant differences. 24-week is too early to access the durability of each treatment and this will clearly an important issue that could show benefits of specific treatments.
  
  variables among the three study arms. However, they were careful to note that longer follow-up is necessary to determine the most suitable treatment in terms of durability.

Comment

There is a clear interest to evaluate Bio-Alcamid and other treatment in clinical trials, where results from all patients together with longer term follow-up can be considered, perhaps in comparison with other lipoatrophy treatments.

Although New-fill has generated successful results with severe lipoatrophy, this can take upwards of 7-8 sessions for some patients. A procedure that required fewer treatments and had greater permanence could be more tolerable and satisfactory in this patient group, who are also less likely to benefit from natural reversal of lipoatrophy, when the etiology is eventually understood. Cost clearly becomes an important consideration, as does the pricing for each compound, when this number of treatments are required in severe cases.

Safety data from larger volume application, particularly non-facial use should also be collected prospectively.

The comparative benefits of different approaches is something that concerns patinet, researchers and clinicians, with durartion to 2 years being probably the minimum useful time point durability.

A meeting on the regulatory aspect of new treatments for lipodystrophy was organised by the Forum for Collaborative Research immediately prior to the meeting, and a report from this meeting was given at both at the Lipodystrophy Workshop and ICAAC conference, and included the aspect of durability as one of its recommendations.

The report from the Forum meeting is available from the website:
http:www.hivforum.org

References

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IB050601-17

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