French Study Clears HAART of Cancer Link in Kids

There is no evidence that anti-HIV drugs cause cancer in adults. However, these medicines are taken by pregnant HIV positive women, and therefore could, in theory, have a negative effect on the fetus and, later, infant. This possibility arises for a number of reasons, including that of rapid growth and development in the fetus and child. During the time in the womb and later in early childhood, human genetic material (DNA) is extremely active as many genes are activated. Exposure to potentially cancer-causing substances such as nukes during this time could interfere with the fetus' or child's genetic material, sowing the seeds for cancer later in life.

Recognizing this, French scientists have been collecting health information on children born to HIV positive mothers. Their most recent analysis of their data suggests that there is no overall cancer risk to children born to mothers who used anti-HIV drugs during pregnancy. However, the effect of certain combinations of anti-HIV drugs has raised concern, so further investigation of these combinations is required.

Study Details

Researchers sought information on 8,853 children born to HIV positive mothers in France between 1990 and May 2007. All the children were exposed to nukes and other anti-HIV agents during their time in the womb and/or after birth. About 65% of the women began taking treatment during their second trimester of pregnancy.

Results

By May 1, 2007, a total of 10 cases of cancer (four girls, six boys) had been diagnosed in children as follows:

• leukemia -- three children
• cancer of the pineal gland (in the brain) or pineoblastoma -- two children
• eye cancer (retinoblastoma) -- two children
• cancers arising in the supportive tissue of the brain (gliomas) -- three children

These 10 cancers were detected, on average, when the children were four years old.

Making Sense of the Data

In general, researchers would have expected about 9 cases of cancer among this number of children if they had been born to HIV negative mothers in France. So the difference in expected and observed numbers of children with cancer born to HIV positive and HIV negative mothers was not statistically meaningful.

Of the 10 children born to HIV positive mothers, five children had tumours in the brain or spinal cord (these constitute the central nervous system, or CNS). Among children born to HIV negative mothers in the same period in France, only two cases of tumours in the CNS would be expected. However, this difference in tumours between the children was not statistically significant.

The researchers did note that four cases of cancer affecting the nerves outside the CNS, the kidneys or other organs/systems occurred in children born to HIV negative mothers during the same period. None of these cancers occurred in children born to HIV positive mothers and researchers do not know why this was the case.

Risk Factors

The risk of children developing cancer in the French study was not linked to any of the following features of the mother:

• geographic origin
• drug addiction
• viral load
• CD4+ count

However, being born severely premature (having spent less than 33 weeks in the womb) increased the risk of a child developing cancer 10-fold.

Compared to children who were exposed to AZT (zidovudine, Retrovir) in the womb, children who were exposed to the following two drugs had an unexpected 12-fold increased risk of cancer:

• ddI (didanosine, Videx)
• 3TC (lamivudine)

The findings about prematurity, and the combination of 3TC and ddI were unexpected.

Key Points

1. Overall, the rates of cancer seen in children born to HIV positive mothers in this study are similar to those seen in children born to HIV positive mothers in Germany and the United States.
2. The overall rate of cancers in these children is very, very low -- less than 0.01%. This is the same rate as seen in children born to HIV negative mothers.
3. The results of the French study underscore the importance of continued monitoring of children born to HIV positive mothers.
4. The benefits of HAART used during pregnancy clearly continue to outweigh any potential risks to the fetus and subsequent child, at least for the first five years of life. Longer-term monitoring is necessary to find out the cancer risk of these children as they grown into adolescents and young adults.

References

1. Anderson BL, Cu-Uvin S. Pregnancy and optimal care of HIV-infected patients. Clinical Infectious Diseases. 2009; in press.
2. Benhammou V, Warszawski J, Bellec S, et al. Incidence of cancer in children perinatally exposed to nucleoside reverse transcriptase inhibitors. AIDS. 2008 Oct 18;22(16):2165-77.

Want to read more articles in the February 2009 issue of Treatment Update? Click here.