NAPWA

It’s been three years in the making, but an Australian trial of polylactic acid for the treatment of facial wasting is about to get underway at last. But while the news is good, there are some important limitations to this project. KIRSTY MACHON reports.

For some time now, it’s been clear that one of the treatment and research priorities for many positive people is polylactic acid for the filling out of facial fat wasting (lipoatrophy) associated with HIV drugs.

Polylactic acid is marketed in Australia and the United States under the name Sculptra, but most people with HIV know it as New-Fill (its previous name). For some years now, it’s been regarded as the leading and most viable candidate treatment for loss of fat from the face — the ‘sunken cheeked’ look of lipoatrophy.

Sculptra has been available in Australia for some time — but at a price. It’s a licensed cosmetic treatment, also used for cosmetic nips and tucks outside of the context of HIV, and the substance is also used to make sutures for babies and children.

However it was French researchers who, six years ago, first reported that polylactic acid, or New-Fill as they called it, could be used to treat facial wasting.

Some time later, a Melbourne surgeon became the first in Australia to train in and begin using polylactic acid for this purpose. At the time, research was beginning to identify the nucleoside analogue HIV drugs, in particular d4T and AZT, as the major risk factor for developing fat loss. However, initial studies were finding that the extent to which you could reverse or ameliorate damage already done by changing treatments or stopping the culprit drugs was limited.

Meanwhile, social research, much of it initially conducted overseas, was beginning to establish what would surely seem obvious to many people living with lipoatrophy: that it had profound effects on self-esteem, body image, and confidence; and, in many communities, the characteristic hollow-cheeked look was seen at least as a marker of at ‘illness’, and in much of the gay community, a signature of HIV.

As one gay man acerbically told Canadian researchers in 1999, “I have been open about my HIV status, but I prefer to announce it myself.”

The Melbourne-based plastic surgeon Dr Brett Archer was one of the earliest proponents of New-Fill in Australia, importing the product and treating HIV-positive people, initially through his clinic and later through an access program set up at Melbourne’s Alfred Hospital, using funds from a state government New Technologies grant. This program has now treated numerous people since its inception.

In other states, a handful of plastic surgeons and even some GPs have also been performing the technique. But with no Medicare reimbursement available, the cost of treatment has varied, with patients footing the cost of the product itself plus surgeons’ fees at varying levels.

This situation has placed the treatment well out of reach of many HIV-positive people, with a standard course of three treatments usually costing between $1500 and $2000. In addition, it seems that different surgeons have been utilising different injection techniques. Some surgeons, such as Dr Archer, have expressed concern, cautioning that some techniques are superior to others.

Against this backdrop, the National Association of People Living with HIV/AIDS (NAPWA) approached the National Centre in HIV EpidemiologyThe branch of medical science that deals with the study of incidence and distribution and control of a disease in a population. and ClinicalPertaining to or founded on observation and treatment of participants, as distinguished from theoretical or basic science. Research (NCHECRNational Centre in HIV Epidemiology and Clinical Research. Based at the University of NSW in Sydney, NCHECR is one of Australia's leading medical research centres and is recognised internationally as a leader in the field of research into HIV/AIDS and viral hepatitis. ) with the suggestion that they develop a study on the use of polylactic acid for facial lipoatrophy. It was felt that a study could not only be an important point of access to treatment, but could provide some of the ‘hard’ scientific evidence necessary to make a case for Medicare funding for this procedure.

Generally, Medicare doesn’t cover elective cosmetic or plastic surgery, sensibly unwilling to open the floodgates to taxpayer-funded facelifts and breast enlargements. But it does fund limited and specific surgical procedures related to the direct effects of illness or treatment — for example, breast implants for women who have had cancer-related mastectomies. But Medicare requires a high level of evidence demonstrating clinical outcomes and cost-effectiveness(Of a drug or treatment). The maximum ability of a drug or treatment to produce a result regardless of dosage. A drug passes efficacy trials if it is effective at the dose tested and against the illness for which it is prescribed. In the standard procedure, Phase II clinical trials gauge efficacy, and Phase III trials confirm it. of procedures before it will fund them, with a strong preference for randomisedA method based on chance by which study participants are assigned to a treatment group. Randomization minimizes the differences among groups by equally distributing people with particular characteristics among all the trial arms. The researchers do not know which treatment is better. From what is known at the time, any one of the treatments chosen could be of benefit to the participant controlled studies to demonstrate the benefits of any treatment.

One of the challenges has been to come up with a trial design that is sufficiently scientifically robust. It might seem, on one level, to be a straightforward enough proposition: someone has lipoatrophy, they are treated with polylactic acid, and then you compare ‘before and after’ photographs to see if they look ‘better’, ‘less drawn’, ‘fuller in the face’, or just ‘not so sick’. A person, after all, knows if they look better, and this can be independently verified by doctors or photos.

Frustratingly, it’s not so easy to come up with a trial design which can unequivocally prove whether polylactic acid treatment improves facial wasting. There are a range of questions to be answered.

• Apart from how a person looks (something usually considered to be subjective, although it may not seem so to the person), how can we really know what is going on? What is the mechanism by which polylactic acid appears to work once it is injected? What does it actually do when injected under the skin?
• How do you more objectively measure that treatment has improved or affected the contours of the face? How long can treatment last or does lipoatrophy eventually return?
• Does treatment work better if your initial fat loss is mild, moderate or severe?
• Is it safe and tolerable?
• And, importantly, do improvements in peoples’ appearance flow on to improvements to their quality of life? For people living daily with lipo, this question might seen superfluous if not insulting, but the reality is, if we hope that this treatment might eventually secure Medicare funding, or if HIV positive people are going to be paying for treatment, then we owe it to the HIV positive community to be sure that it actually works and lasts and that it makes a difference.

How this study will work

The process of developing a protocolA study plan on which all clinical trials are based. The plan is carefully designed to safeguard the health of the participants as well as answer specific research questions. A protocol describes what types of people may participate in the trial; the schedule of tests, procedures, medications, and dosages; and the length of the study. While in a clinical trial, participants following a protocol are seen regularly by the research staff to monitor their health and to determine the safety and effectiveness of their treatment which satisfies the varying needs and expectations around this study has been difficult, with researchers, doctors and community activists all contributing to a sometimes impassioned debate. An important part of the process, and one of the reasons the study has been so long coming, has been securing funding.
The license for importing polylactic acid into Australia was originally held by a small Australian company called New-Fill. Then, about a year ago, the product was acquired by a subsidiary company of the international pharmaceutical company Aventis, who now market it as Sculptra.

As part of the study, Aventis will supply treatment, at reduced cost, to cover 100 study participants. The remaining funds for the study are being supplied by the manufacturers of most of the major HIV antiviralA medication or substance which is active against one or more viruses. May include anti-HIV drugs, but these are more accurately termed antiretrovirals. drugs, an allocation from ACON, and in-kind support for the running of the study through NCHECR.

Apart from the cost of the product, study expenses include the training of plastic surgeons who will administer the treatments. In addition, assessment of how treatment is working will include measuring changes to the contours of the face through a technique called spiral CT scanning. For this, study participants will be required to travel to hospital sites set up in each state for these assessments.

No doubt the most contentious issue in this study is the limited numbers. For financial and logistical reasons, it is not possible for the study to provide access to Sculptra for all patients who would be eligible, interested or likely to benefit. To do so would require a substantial addition to the current budgets, and securing such funds, if it were feasible at all, would have effectively meant delaying this already long-awaited trial even longer.

Through NAPWA and the national Treatments Policy Group, NCHECR has sought community advice about the study, in particular about how to allocate the 100 available places across the trial sites in the fairest and most transparent manner. Several proposals were considered, including the random allocation of eligible patients by a lottery: while technically the fairest proposal, this was eventually ruled out as it would have involved the screening of many more eligible patients than would be able to obtain places — requiring people to travel to sites and undergo tests without any guarantee of a place.

In the end, a steering committee including community representatives and researchers opted to distribute the places evenly across each of the general practitioner and hospital sites involved in the study. There will be 18 high HIV caseload sites in Brisbane, Sydney, Adelaide and Perth. Melbourne, which already provides treatment through the Alfred Hospital’s access program, retains its state-based program.

In the first instance, each site will receive an allocation of four patients, and will be given a period of six weeks to screen and enrol these patients, from the time the site receives approval from its ethics(In clinical trials) The process of determining that a proposed clinical trial conforms to a wide range of moral, scientific and ethical standards, to ensure that participants in the trial are not abused, mistreated or unfairly taken advantage of. Before a clinical trial can go ahead, it must be given approval via an independent ethics process. committee. At the end of this period, the remaining places on the study will be distributed among those study sites which have filled each of their first four places. Sites which don’t use all four places obviously won’t go into this ‘second round’.

Once enrolledThe act of signing up participants into a study. Generally this process involves evaluating a participant with respect to the eligibility criteria of the study and going through the informed consent process. in the study, participants will be randomised (allocated by chance) to one of two study arms — either to be treated with Sculptra straight away, or treated following a delay of six months. This is to help determine when to best use the treatment — to see if there is evidence for any benefits to treating people in earlier stages of lipoatrophy.

Broadly, to be eligible for the study, you need to meet a number of criteria.

• Your degree of lipoatrophy or fat loss needs to be classified by you and your doctor as moderate or severe.
• There are limitations around the use of certain substances, including some growth hormones and steroids, within six months of the study, as they might independently cause changes to your face, and make it hard to determine if it’s these or the polylactic acid injections which are responsible for any changes.
• You need to be over 18.

There are other criteria which should be discussed with your doctor. In addition, it’s important to realise the study requires commitment from participants, who must be willing and able to travel at regular intervals to the main sites (mostly in hospitals) where the injections, facial scanning and other procedures will be carried out. Your normal GP won’t actually do the injections, but will be responsible for your regular clinical care during the study.

The study and follow-up period is two years.

Frequently asked questions

When does the trial start?

At the time PL went to press, the start date for the trial was not available, however we anticipate that recruitment will commence in August, and continue until all places have been filled.

How many people will get into the study?

There are 100 places — in NSW, Queensland, South Australia and Western Australia.

How come there are no regional or rural sites?

For the study to financially and practically feasible, injections need to be done by a limited number of trained plastic surgeons. The sites were chosen to practically assist this, because the injections will take place in hospitals or clinics in Brisbane, Sydney, Adelaide, and Perth.

If I can’t get onto the study, how can I get treatment?

In Victoria, free access continues for people eligible for the Alfred Hospital program. In South Australia, Western Australia, Queensland and New South Wales, some surgeons and general practitioners are trained and able to conduct this procedure. The cost for this varies. The treatments officer at your local PLWHA organisation or AIDS council should be able to advise on the situation in your state.

Is there any plan to increase access outside the study?

NAPWA plans continuing discussions with Aventis once the trial is running to help negotiate arrangements for further access or supply. As well, NAPWA intends to talk to other service providers and state-based HIV groups who may be able to assist in providing other options for positive people not in a position to pay the full private costs.