February 26, 2002
In the evening session entitled "Controversies in HIV therapy," Dr. Judy Currier reviewed the controversial and challenging aspects of managing antiretroviral therapy during pregnancy. While both the U.S. Public Health Service and the British HIV Association have published guidelines, Dr. Currier did a wonderful job of exploring the difficult and controversial areas that have not been well addressed in consensus guidelines.
The focus of her talk was on balancing competing imperatives. One of these is the need to balance the competing goals of preventing transmission from mother to child and the need to treat the mother for her lifetime and not compromise her options.
Another issue is the safety and efficacy of medications for the mother. Yet another is the safety of the medications for the infant, who will be exposed to potentially toxic drugs in utero. The goals therefore, are to have a healthy, uninfected baby with a healthy mother who will not have compromised her future treatment options.
Dr. Currier reviewed a variety of data that clearly demonstrated that the number of drugs used by the mother is associated with decreasing risk of transmission. Although low viral load is a predictor of low risk, she reviewed data that showed that, even at very low maternal viral loads, there is an additional benefit to combination therapy.
Caesarian section, when done electively, also has an additional benefit for women with no therapy or on AZT monotherapy. However, in data reviewed by Dr. Currier from the PACTG 367, a caesarian section provided no demonstrated additional benefit for women on combination therapy.
Breast-feeding remains a troublesome and controversial issue. If breast-feeding continues for up to one year, an additional 8-14% of children not infected at birth will be infected. In recent studies, such as the HIVNET 012 study, it is clear that the additional transmission due to breast-feeding does not eliminate the benefits of short-course intrapartum therapy with nevirapine. Withholding breast-feeding, however, in many cases, is not simple or practical, and may lead to increased child mortality from infection.
The limitation of current short-course therapy such as the use of nevirapine or short-course AZT/3TC is the emergence of resistance. This resistance may limit the mother's future options. When possible, Dr. Currier stated, fully suppressive regimens such as triple therapy should be used both to maximize the benefits for mother and child and to prevent the emergence of resistance.
Safety of any treatment for either mother or child was reserved. Although there are some conflicting data, to date there are no conclusive reports of any significant toxicity from any of the above drugs for the mother. However, prolonged use of d4T and ddI has been associated with lactic acidosis and hepatic steatosis, although this has not been shown during shorter-course therapy. AZT-based therapy might also be associated with increased serum lactate. To date, there is no evidence of protease-inhibitor-induced diabetes during pregnancy, but this continues to be an area of concern.
Recent data looking at the potential teratogenic effects of antiretrovirals were reviewed, and there is no evidence to date of an excess risk. However, it is important to realize that the available data are limited, and Dr. Currier urged continued reporting and study of this issue. She reminded us that efavirenz and hydroxyurea do cause birth defects in animals and should be avoided during pregnancy.
Dosing of antiretroviral drugs during pregnancy is problematic. As reviewed during the session, there are many changes in drug metabolism during pregnancy. The few studies available suggest that standard dosing may not be adequate during pregnancy, but further research, and, possibly, therapeutic drug monitoring are needed.
As we become more conservative about when to begin HAART, a critical question becomes what to do for a woman who is diagnosed with HIV during pregnancy but has a CD4 count that would not ordinarily lead to treatment. Dr. Currier's personal opinion (which I share) is that the best option may be to use a fully suppressive three-drug regimen during pregnancy, perhaps waiting until after the 12th week of pregnancy, but to consider stopping all drugs after delivery.
There is no shortage of difficult areas that remain, but Dr. Currier concluded with a plea for more research so answers can be based on data, and not opinion. Still, it is worth remembering how far we have come in our ability to care for women with HIV, both during their pregnancies and when preventing transmission to their infants.