Twin pregnancies involve greater risk of mother-to-child HIV transmission unless potent anti-HIV drugs used

Twin pregnancies involve an increased risk of mother-to-child transmission of HIV, according to the results of a large French study published in the May 11^th edition of AIDS. However, the risk was only higher in the period before effective anti-HIV treatment became available, and since 1997, the risk of mother-to-child HIV transmission has been equally low for both twin and single pregnancies. Known complications of twin pregnancies, especially premature rupture of the membranes, were associated with HIV transmission to a twin, and the investigators found that the twin born first was significantly more likely to acquire HIV infection than the second twin, probably because of exposure to HIV in the birth canal.

There has been little previous examination of the risks of mother-to-child transmission in twin pregnancies. The only study to examine this issue was conducted in the 1980s, before antiretroviral therapy was used to prevent mother-to-child transmission, and involved only 22 pairs of twins. It found that twin pregnancies did not involve any increased HIV transmission risk.

Nevertheless, it is well known that multiple pregnancies have an increased risk of complications, such as premature labour or rupture of the membranes, and such complications are known to increase the risk of mother-to-child transmission of HIV.

It is important to establish if multiple pregnancies involve a greater risk of HIV transmission because the incidence of multiple pregnancies has increased steadily in industrialised countries over the last two decades. It is thought that this is linked to increased maternal age and the wider use of methods of assisted conception.

French investigators therefore performed an analysis of the rate of mother-to-child transmission of HIV in twins compared to single births (or singletons). They analysed data from 9,262 pregnancies between 1986 and 2004 at 90 hospitals across mainland France. Data were also gathered on the mothers’ demographics, their obstetric care, rupture of membranes, and use of antiretroviral drugs to prevent HIV transmission.

Investigators identified three time periods, according to the type of antiretroviral therapy used. Before 1994, no antiretroviral drugs were provided to mothers during pregnancy. Between 1994 and 1996, mothers were provided with AZT (zidovudine) monotherapy, and after 1997 potent combinations of anti-HIV drugs were provided during pregnancy.

A total of 192 (2%) deliveries involved twins. The proportion of twin deliveries increased significantly over time from 0.6% between 1984 and 1987 to 2.5% between 2000 and 2004 (p = 0.003). The investigators noted that over the 20 years of the study, there was a significant increase in age of mothers and in the proportion of African mothers, factors both associated with twins.

As expected, the investigators found that twins were significantly more likely to be born prematurely (before week 37) than singletons (p

The investigators then looked at the use of antiretroviral therapy during pregnancy, and found that the median duration of antiretroviral use by pregnant women was four weeks shorter for mothers expecting twins than singletons (13 weeks versus 17 weeks, p

In the entire period of observation, approximately 10% of twin pregnancies involved mother-to-child transmission to one or both children. In just over 7% of cases, only the first child was infected, in a little over 1% of instances the second twin was infected, and in just over 1% of pregnancies, both children were infected. The investigators comment: “The greater risk of transmission to first twin is indirect evidence for…birth canal exposure.”

This 10% transmission rate compared to an overall 6% rate of mother-to-child transmission in singletons, a difference of borderline statistical significance.

However, the investigators found that in the period before potent HIV therapy was used during pregnancy, twin pregnancies were significantly more likely to result in mother-to-child transmission than single pregnancies (28% versus 14%, p = 0.03).

An extremely low rate of mother-to-child transmission was recorded after 1997, and did not differ between twins (1%) and singletons (2%). The only case of transmission involving a twin in this period was in a mother who did not start receiving HIV care until the third trimester of pregnancy, beginning HIV therapy at week 36 of gestation, and giving birth via an emergency Caesarean at week 38 when she had a viral load of over 8,000 copies/ml.

Premature rupture of the membranes was identified as a particular risk factor for mother-to-child transmission in twins. They found that premature rupture of the membranes occurred in 50% of instances of mother-to-child transmission involving a twin compared to just 17% of cases involving singletons (p = 0.01). In the absence of premature rupture of the membranes, the rate of mother-to-child transmission was similar for both twins and singletons.

“In cases of multiple pregnancies in HIV-infected women, management must take into account the risk of preterm premature rupture of the membranes and preterm delivery”, conclude the investigators. The add, “we would recommend starting effective antiretroviral therapy no later than the beginning of the second trimester.”