Karen Beckerman
The program at San Francisco General Hospital for perinatal care focuses strongly on maternal health. This strategy has reduced their incidence of vertical transmission to practically zero, and they believe that 'nothing is more important to a child than the health of its mother.'
Something that other speakers have raised and which I would like to additionally stress - is that pharmacokinetics of antiretrovirals in children is extremely important. Many other aspects of HIV care are also important for babies and children, however nothing is more important to the health of a child than the health of its mother. It is from this perspective, with a very strong focus on maternal health, that our programme in San Francisco, at the Bay Area Peri-natal AIDS Centre has grown up since it was founded in 1989.
We have benefited in many ways from being in San Francisco. We have the support of the HIV community, access to the cutting edge of HIV therapy, and access to the tremendous HIV advocacy that has been a long-standing tradition there. Compared to the other presentations we are somewhat behind in terms of support for families.
For example, I just had to take care of three women in the last year, all of whom had HIV-uninfected babies but none of whom were able to take their babies home with them. And they will probably never live with their babies in their entire lives. This kind of tragedy cannot be averted by all of our pharmacological interventions, but it can be helped with very important programmes like the ones we have just heard about.
It is important to remember the first results from what I now call an 'historic relic' - ie the 076 study. At the time it was a miracle - the first sign of true hope in an otherwise very bleak picture. But now we have moved far past that in terms of HIV therapy and the idea now of giving monotherapy to anybody except to pregnant women or uninfected babies is really an anathema. And it should become an anathema to pregnant women also. The treatment protocols that I will be discussing are controversial, but I want to make it very clear that pregnant women deserve no less than the absolute latest standard of care and optimal therapies.
We knew from the 076 study that we could cut the rate of vertical transmission using AZT by itself prophylactically for both mum and baby. What we also knew by the mid 1990s was that viral load was highly predictive of progression to AIDS. What we then hoped (although none of us really knew it yet) was that if we could reduce viral load we could perhaps lower a person's risk of progression to AIDS or to death.
In the case of our unit, where we were taking care of pregnant women, we did not know if lowering a mother's viral load by use of these potent combinations could also perhaps benefit the baby? Many people were thinking of HAART therapy as a threat to neonatal immunal health, but we saw it as a chance to benefit the babies health. I would stress to you some of the reasoning behind this because we were really in an unknown area. However as obstreticians, we did know that the baby is exposed to enormous amounts of mothers blood during pregnancy. In the third trimester alone a foetus is exposed to 80,000 litres of maternal blood. In the case of an HIV infected mom that means 80,000 litres of virus. So we reasoned that it couldn't help but be of enormous protective benefit to the foetus to aggressively lower plasma viremia during gestation in the second half and later in pregnancy.
Of course we had concerns about the developing foetus and we were all very nervous about what might happen in terms of birth defects. Our first mothers using HAART therapy and PIs, were women who otherwise would have been dead without that therapy, they all had advanced HIV disease, AIDS and a history of PCP. So, there was not really much of an option in discontinuing their HIV treatment. We have since given the mothers the option to discontinue therapy before or during pregnancy, although none have chosen to do this yet.
We also developed an attitude towards the care we give our patients which I tried to sum up in a sort of Bill of Rights for HIV-positive mothers. This is for access to current state-of-the-art therapies for both HIV disease and pregnancy. In terms of pregnancy we can't always reach these goals, but access to pre-diagnosis discussion with the mum about what she wants for herself and her foetus. It should included Lamas classes (pre-natal) orientated towards HIV where they don't have to sit hour after hour learning about the beauty of breast-feeding! Also (and this is very important to the women that I take care of) knowing that when they are admitted San Francisco hospital, the body fluid protections that will be taken by their carers are identical to those that every patient receives. In other words every patient in our hospital is treated as if she could have a fluid borne pathogen that could affect contacts - HIV mums are treated no differently to any other mother. This is a great comfort to everyone.
Education and counselling is the centrepiece of our work. It is what we spend most of our time on in our very long and frequent discussions. Mothers then know that they are in charge and they will determine what therapies they will take during pregnancy (and what therapies they don't take). Empowerment is a very important part of our orientation. This may seem altruistic of us, but it is actually quite practical - there is no way that you can force anyone to take therapy that she doesn't want to. All your going to do is to force her to tell you that she is doing what you want her to do.
We find that when mothers know this, they are very honest in telling us about their adherence, about how many meds they really did miss that week. This can explain a viral laod that is inexplicably high and it really is an enormous boon to our relationship with individual and collective patients.
But our treatment guidelines have evolved since the 076. When in 1994 AZT was available to all mothers, our clients quickly took this up, but by 1996/97 we shifted to a focus of the use of antiretrovirals to control the mother's viral load.
We no longer give two drugs to anyone with the rare exception of d4T/ddI (not prescribed since the recent FDA caution), and an even rarer exception of AZT being given to mothers in early stage disease, when mothers feel that they are just completely unable to consider triple therapy.
The standard of care for HIV-positive people is now a minimum of triple therapy, and it is our philosophy that it should be the standard of care for pregnant women. With early disease, mothers can always stop their medicines after they deliver. But it is our charge to safeguard the mothers' health, to enhance their survival, and our duty to make sure the babies that we care for are delivered uninfected of a mother who is not in the process of developing completely unnecessary antiretroviral resistance. Recently we've had three mothers deliver on more than four drugs.
So can you really control maternal viral burden in pregnancy? You can, but you can't do it with no drugs or just one. Two drugs can be effective but we all know from other adult studies that the development of resistance is extremely likely - and this will then compromise the mother future options. Data has appeared in pregnancy showing that about 80% of women who receive AZT alone will develop broad-spectrum nucleoside resistance.
Not surprisingly, the benefits from triple therapy is completely predictable from what is well known in adult and child studies. We are benefiting mother's health tremendously by treating her disease accurately with a minimum of three drugs
We have been talking a lot about mum's health, but what about the effect upon baby of all these meds? For example there were early concerns about prematurity with PI use. Even with our own data the relatively low numbers that we see mean that the results do not achieve statistical significance. However, there is no documented increase in prematurity going from zero to three or more antiretrovirals. In fact our babies who were most likely to be premature were born to those mothers who received no drugs during pregnancy, and we see no decline in gestational age in comparison to antiretroviral use.
With transmission rates too, our small numbers of transmissions mean they are lacking in statistical significance. I therefore reviewed the available international literature, to see if what we had witnessed in San Francisco was statistically true. Combined reports from thirteen different studies saw data very similar to ours with falling transmission rates as number of antiretrovirals are increased. The difference between three or more, or two drugs, still has overlapping confidence intervals, but I expect that as we gather more numbers internationally that we will see that the best thing for baby is three or more drugs.
The issue of ruptured membranes, very beautifully studied by Landesman and colleagues in the WITS protocol, demonstrated that with increase in hours of ruptured membranes there is an increase in probability of transmission. This concern has of course led to the common practice in many areas of elected caesarean section to prevent HIV-transmission. Our data from San Francisco was gathered in a population where elected caesarean section was available only for the last ten deliveries. The uptake in these cases has been around 25%. We do not withhold caesarean section for those mothers who want it, but for those mothers with good virological control we advise them that there is no demonstrated benefit for them or their baby from an elected surgical intervention.
And finally I must address why the most popular therapy for pregnant women in America is still Combivir alone. I still attend professional obstetrical meetings where leaders in the field (though not experienced in HIV), talk about the beauties of Combivir and how ideal it is for pregnant women.
I answer that just because you hear it and from someone who appears to be in a position of authority it doesn't mean it is true - in fact it is very wrong. A woman who receives Combivir alone in pregnancy regardless of her stage of disease, has a four out of five chance of becoming resistant to all nucleosides for the rest of her life.
This is not a tolerable action. Many of us would call it not only outside of the standard of care but malpractice.
Dr Karen Beckerman is Associate Professor of Obstetrics, Gynaecology and Reproductive Sciences at the University of California, San Francisco and has been a Visiting Investigator at the Gladstone Institute of Virology and Immunology since 1997. Her special interest is maternal health in the HIV pandemic, and treating HIV disease during pregnancy.
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