Long choosing, and beginning late

So how can we do a better job of getting people onto life-saving antiretroviral therapy (ART) sooner, before they fall sick, and risk death as a result? I do have one or two ideas, Tom, if not solutions.

Clearly the first challenge is to identify people infected with HIV earlier. Certainly easier said than done, and as I've discussed before our current 'voluntary counselling and testing (VCT)' program is totally failing in this regard. Effectively passive, it's really provider initiated in most cases, detecting people only after they have to be admitted to hospital with AIDS-related conditions. But from the many questions I get (but rarely answer), it does seem many people are more ready to go to the ubiquitous private labs (Prodia is the best known) for testing, often very soon after their risky activity. Sadly they are usually poorly counselled and rarely referred from such labs.

As far as I know, these labs are not included in the national AIDS action plan. Would it not make sense to recognise their role, and provide guidelines and even accreditation to assist them to do a better job?

Once identified, how do we get them into treatment - and retain them? Clearly we need a better referral system. But if we get them into care soon after they are infected, we know that it may be five years or more before they need ART - based upon the current criteria. It's clearly extremely difficult to expect them to return for regular follow-up - more so since (as I have noted) they'd prefer to forget that they are living with HIV.

The solution is simple - and now increasingly urged: start ART immediately. Hardly a day goes by now, but some study does not report the benefits of much earlier start, and the risks of delaying. Prof. Joel Gallant from Johns-Hopkins, one of my HIV care heroes, was asked recently, if he became infected, when would he start ART. His answer? "Immediately" (Suppose that you were positive). And this is even more important for people with co-infections such as viral hepatitis.

Studies by WHO experts have shown that starting ART immediately would save money in the long term. The challenge of course is in the short term. Even the WHO shows no signs of 'putting its money where its mouth is.'

Other approaches? I am convinced that one barrier to starting ART is that people are doubtful that they will be able to adhere to the every 12-hour schedule of current first line regimens. But in fact the current standard first line regimen in the rich world is much easier: one pill once a day before going to bed. Most people go to bed every day, so they don't need complex reminders, or concern about being late. Clinton Foundation can buy such a pill for little more than US$300 per patient per year - less than the government pays Kimia Farma for the current standard first line regimen. And of course this one-pill-once-a-day ART solves the problem of taking ART during the fasting month.

I've never been a strong supporter of the concept of 'case managers' here. But since we have them, why don't we require them to play a more active role in retaining people in care, especially those do not yet need ART? Get help from peer support groups if they lose contact. Of course they should be doing this already for those on ART, but...

We can - and should - do all we can to make sure that no more Fredy's die from starting treatment late...

Babé

Delays breed dangers

Sadly, another heavy loss this week. Fredy Malik, Indonesian Drug User Activist since 2002, died of AIDS. I did not know him well, but it is clear that he had played a crucial role in the development of harm reduction in Indonesia, in Asia, and probably more widely. It is due to people like Fredy that Indonesia is among the leaders in this field.

James Blogg from the AusAID-funded HIV Cooperation Program for Indonesia (HCPI), who I ran into earlier this week, noted how sad it is that many Indonesian drug users with HIV leave it until very late to start antiretroviral therapy (ART). This was apparently the case with Fredy. Seems that this has been a challenge in Bali since the start. In around 2003, the Bali provincial AIDS Commission agreed to provide funds for ten activists to start treatment. But almost a year after the launch, only two or three people had taken up the offer, even though many clearly needed it. In meetings with HIV-positive people, it became clear that they were extremely worried about the reported side effects, to the extent that they were scared to start therapy.

Part of the problem is the not infrequent cases of what is called Immune Reconstitution Inflammatory Syndrome or IRIS. Many symptoms of infections, for example fever, are a result of the response by the body's immune system to the infection. But when the immune system is severely damaged, it is unable to mount a response, and thus people with advanced HIV infection frequently appear quite well, with no serious symptoms. However once they start ART, the immune system starts to recover, and quickly responds to these 'masked' infections. The paradoxical (and very distressing) result is that within weeks or months of starting ART, many people who start late experience a worsening of their health, sometimes some really nasty symptoms (such as loss of sight), and not a few die.

The solution is to start (as recommended) before the immune system becomes so badly damaged. For many, this is not an option, since they are only diagnosed HIV-infected in this condition. But many, such as Fredy, have been long aware of their infection, but have delayed starting. To many this seems amazing; why would they be so loathe to start life-saving therapy, especially when it is free? It's a no-brainer, no?

Actually, we often underestimate the psychological barriers to starting ART, especially for those who have lived several years without any health problems caused by HIV. Starting ART can seem like capitulating to the disease, accepting that HIV has won and the journey to AIDS is near its end. Not only that, but we must accept that HIV is now going to control our lives. ART: don't leave home without it. Be reminded that we have HIV twice a day when we open our pillbox. Face unpleasant side effects, both short and medium term (and worry about long term ones which have yet to appear). Agonize over whether we can really develop the discipline to take the meds exactly as prescribed every twelve hours without ever forgetting. Worry about sustainability of supply of ARVs, by a system which has demonstrated a clear inability to guarantee availability. And face the ever present threat of treatment failure, causing the development of resistance and the need to change to a more complex and expensive regimen. No, we should not underestimate the challenges of starting therapy.

In fact, in this regard those diagnosed late may be better off. They aren't given time to think about it. 'You need to start ART in a couple of weeks if you want to survive.' Still a decision, but more easily reached.

What can we do to help the Fredy's to start earlier? This post has gone on long enough. I'll return to this point later.

Babé

PS: Yvonne A. Sibuea, General Coordinator, PERFORMA, has posted 'In Remembrance of Fredy Malik.' on a mail list. I cannot link to this, but if anyone would like me to send them a copy, please let me know.

A bridge too far

Are the antiretrovirals (ARV) produced in Indonesia equal to the imported ones? This question is often asked in the various forums and during meetings with people with HIV here. I have usually answered that the generic drugs industry in Indonesia is said to have a good reputation, that the Indonesian Food and Drug Administration (BPOM) is said to do a good job of monitoring the industry, and anyway, 'the proof of the pudding is in the eating': my friend Yuni has been on locally-produced ARVs for almost seven years now, with a CD4 rise from 17 to more than 800, and a consistently undetectable viral load. In addition, it seems that all of the ingredients are imported from standard sources (in China?), and are only assembled and packaged here.

But now I'm not so sure. The headline in today's Jakarta Post says it all: "Consumers warned of ‘substandard’ generic drugs." The article even specifically refers to Kimia Farma (KF, the producer of the generic ARVs here) - although it is not clear that there is any specific concern with that company.

Actually. a presentation "Generics: access, efficacy and quality" by Andrew Hill from Liverpool University at the recent HIVNAT Symposium in Bangkok has already raised worries in my mind. Andrew raised the concept of "PK bridging", which is used to "prove" that generics are in every way equivalent to the original drug. There is a 'gold standard PK bridge' (picture of the Golden Gate), that is employed by reputable companies. There are 'other forms of PK bridging" (picture of rickety footbridge) that are 'much less stable." Several elements of this bridge should raise red flags. For example, unpublished trials - I have yet to see any data about trials by KF. And why are they not WHO approved - do KF practices meet the standards? Where can we get answers to these questions?

Sometimes I'm scared to dig too deep...

Babé

Natural selection

In the training just completed, as usual we discussed how to select recipients of antiretroviral therapy (ART). Of course, in an ideal world, everyone who needed ART (or at least those who meet the criteria) would get it free of charge. And currently that is the situation in Indonesia, although of course not in every third world country. But according to the Indonesian communicable diseases directorate (CDC), today less than 11,000 people are being treated.

A couple of years back, Dr Sigit, the head of the AIDS Sub-Directorate at the CDC, estimated that by 2010, 100,000 people would need treatment. Given an estimated 273,000 people living with the disease in Indonesia, that number is not unlikely. Of course it is most unlikely that the current testing policy will identify even half of this number, but even that would suggest a possible fivefold increase in those on ART by the end of next year. Such a scale up is by no means impossible; several countries in Africa have increased their numbers on ART more quickly. But what about funding?

We are told that the MoH now pays Kimia Farma Rp 400,000 per person per month for the first line regimen. That amounts to more than US$ 400 per person per year. Thus currently the government is paying moer than US$ 4 million a year for first line drugs - and having difficulty finding the cash. Only a few months back, Kimia Farma stopped shipping the drugs, because they could no longer afford to provide credit to the government - who owed them for almost 9000 patient-months of one drug. A disaster was only avoided by the National AIDS Commission paying some of the bill.

So, if we have difficulty supplying the drugs for 10,000 people, how on earth will be find the cash for 50,000? Unless someone comes up with a solution, there will have to be some rationing, which means selection, which means that someone must decide who lives and who dies. In our training session, which is aimed at opening the minds of some of the activists, we discuss some of the options for selection: priority for pregnant mothers, for example, or for families with young children. We discuss whether the current system of providing ART free to all, regardless of ability to pay, can be sustained, and if not, how we identify those who should contribute. (As an aside, many of the participants spend more than Rp 4 million a year on cigarettes!)

As a theoretical exercise, this session is always interesting. Few participants have thought about this, and for the many who have already suffered through drug shortages, it's anything but theoretical. And does cause some anxiety.

But is this scenario likely? Difficult to tell. The Clinton Foundation claims that it can procure the same first line regimen oat under US150 per person per year. At this price, the current budget could provide ART for more than 25,000 people. And prices continue to dive. In addition, several local administrations are considering some form of funding for ART, and it should be possible to persuade some employers to come to the party. Then there's the insurance companies... If we coordinate all of these sources, we should be able to cope.

On the other hand, an increasing number of people will be needing (still pricey) second-line therapy as their current regimen fails. And every year the number needing ART will increase. The spectre remains...

Babé

...profit the professor naught

Returning to Michael's article in Inside Indonesia. I'm sure that anyone who is involved with HIV in Indonesia has identified 'Professor Setiawan'. I fully understand the frustration of 'Nuraini' and Michael, and there's no point in me trying to defend the doctor. Nuraini's report is unfortunately by no means unique. We have frequently suggested ways that doctors could spend more time with their patients, in particular those recently diagnosed - and their families. The situation in this case is exacerbated by the fact that the doctor concerned has a high reputation - in many ways justified. So many patients, or more often their families, insist on being treated by the 'Prof'. The result? The sixty patients at every surgery that Michael referred to.

What saddens me more (and makes it more difficult for me to be balanced) is that I have known this doctor for more than 18 years. I first met him on the night my partner was diagnosed with HIV, and I immediately felt we were in good hands. My partner appeared very comfortable with him. As the end came, the doctor on a couple of occasions visited my partner at home, and he took the time to attend the 40-day 'selamatan' following his death.

In the following year, I volunteered with the AIDS service organization the doctor had co-founded, and he mentored me as we developed the program to support people living with HIV in Jakarta. He greatly encouraged me in my efforts to offer information in the vernacular on care, support and treatment for people with HIV. Although I left the organization after a couple of years, we continued (and continue) to meet, and I think our mutual respect remains.

However, the relationship did start to suffer as we tried to encourage people with HIV to develop more empowered relationships with their doctors. Sometimes his patients would contact me with concerns, and I would try to provide them with informed advice. On their next visit to the doctor, some of them would begin with 'Babé says...', clearly not an ideal way to start a discussion. I know this doctor is very concerned about interfering between other specialists and their patients, even when the patient concerned is also is also one of his - I sometimes think this is taken to the extreme, particularly where the other specialist has limited experience treating people with HIV. But given this, I can understand that he doesn't appreciate me 'interfering' in his relationship with his patients. This is not, of course, my intent, and generally I am only attempting to provide the most up-to-date information, and always tell them to discuss this with their doctors before making any decision.

What can and should be done by us 'bulé' (foreigners) to address these problems? Sometimes I feel I'm on the horns of a dilemma. Has Michael's action helped? I'll return to this subject later...

Babé

...positive endeavors...

Some of you may have read Michael Buehler's article "No positive news: People living with HIV face corruption and incompetence in the health system" in the last issue of Inside Indonesia. I am very aware of the case he reports, and sadly it is only too typical. We have been fighting these problems since antiretrovirals (ARVs) first became available in Indonesia over five years ago.

At that time, we had to make a decision: wait for a trustworthy system to be put into place, or try to force things. We took the latter approach. although not without trepidation. One doctor with an international agency warned that we were taking a big risk, but the idea of telling people who were dying, "Just hang on, we'll get you treatment Real Soon Now" just didn't seem to be an acceptable solution. We formed an ARV fund to buy ARVs for activists, as I recounted in the story of Mama Dora. We purposely chose recipients from outside Jakarta - indeed one of the first, in late 2003, was from Merauke, Mama Dora's home in Papua.

He had come to Jakarta for a meeting of people with HIV, fallen sick with a very low CD4 count. So we started him on ART at one of the hospitals here in Jakarta. Luckily MSF had just set up what turned out to be a highly successful HIV treatment program in Merauke, so I rang the MSF doctor to tell her that he was returning to Merauke to continue his therapy. She was quite upset, saying they were not yet ready. But, as they say here, 'apa boleh buat' (what could she do?). They had to become ready fast.

But I must say, I did assume that a workable and working program could be set up in a few years. The fact is that the Indonesian ART program is unable to support only around 10,000 people, while several smaller countries in Africa have in the same time scaled up to provide ARVs to over scores of thousands each - why? I know, there are a different set of challenges, but...

Should we have waited? I think we would still be waiting - and most of those who are (reasonably) complaining now would not be alive...

I'll return to some of the other points in Michael's essay tomorrow.

Babé

Eating the air on promise of supply

The supply chain for antiretroviral drugs (ARVs) in Indonesia is a real mess. Almost every month, at least one hospital runs out of one or more of the drugs. And about every three months, the country runs out. The problems vary from orders not placed, no money, poor inventory control and reporting in the hospitals, lost reports at the centre, and on and on.

I've talked before of the reluctance to start therapy by those who really need it. Not surprisingly, one common reason is that they are scared about sustainability of supply. They've been told that if they miss doses, they'll become resistant, and they wonder what they'll do when the supply line suddenly becomes empty.

Naturally, there's a wider fear that the government will lose interest in fully subsidizing ARVs, particularly as the numbers grow. There is no long-term guarantee; not only is the government budget only valid for a year, the actual funds are usually only released six months or so into the financial year, and have to be spent before the end of the year. Impossible to manage.

Of course the alternative to starting, albeit riskily, is clear: fall sick and die. AIDS is not forgiving! When ARVs first became available, we tired to guarantee supply for 12 months; they could at least they would survive for another year. But that's really not acceptable.

The price of ARVs will drop. The last information I had was that the government is paying Kimia Farma around $500 per year for the basic triple-drug regimen. This is now available on the international market through the Clinton Foundation for only $100. That's less than most of our friends spend on cigarettes in a year. Is that a reasonable comparison?

Would we be better without subsidy, but controlling the supply ourselves?

Babé

Starting is the hardest part

When to start antiretroviral therapy (ART)? This controversy dates back to David Ho's "hit early, hit hard" campaign soon after ART was first introduced in 1996. This was replaced by a very conservative approach, which basically said "wait until people are sick."

Now the various AIDS societies and government bodies in the West seem to be vying with each other to see how fast they can ease the starting criteria. (It's difficult to find the right words; they are lowering the threshold by raising the CD4 count at which ART should be started).

But the fact is that, even if the WHO - and the Indonesian Ministry of Health - move in the same direction, most people starting ART here will not be affected. Why? Because most continue to be diagnosed with HIV only after they fall sick with a serious opportunistic infection. They would meet almost any criteria for starting ART.

But this is not the only barrier. Even those who are aware of their infection earlier are often reluctant to start. They may be worried about side effects, or about sustainability of supplies of drugs, or continued commitment by the government to provide the treatment free-of-charge. But I think we often underestimate the mental block: starting ART is an admission of failure.

An admission that the virus is getting the better of us (we've been persuading ourselves that healthy living - or perhaps jamu - is going to keep it at bay); an acceptance that our lives are going to be controlled by our drugs (never leave home without them); and an acknowledgement that twice a day when we take our drugs, we'll be reminded that we're living with the virus (we've probably been trying to forget this for the last few years).

We're all great procrastinators, and we all hate to fail. This is another time when it's easy to delay a decision.

Babé