Antiretroviral Therapy Interruption during Pregnancy Increases the Risk of Mother-to-Child HIV Transmission

Evidence continues to accumulate indicating that interruption of antiretroviral therapy (ART) has deleterious effects. According to an Italian study published in the March 23, 2009 issue of Clinical Infectious Diseases, stopping treatment during pregnancy can increase the risk of mother-to-child HIV transmission.

With prophylactic therapy, such as the ACTG 076 regimen of zidovudine (AZT; Retrovir) given during pregnancy, labor, and to the baby for 6 weeks after birth, the risk of perinatal transmission has decreased dramatically. But combination therapy can reduce the risk even further by fully suppressing HIV viral load, and the latest DHHS treatment guidelines recommend that pregnant women should receive a complete ART regimen even if they would not otherwise need treatment based on CD4 cell count.

Many experts, however, have traditionally advised pregnant women on ART to interrupt therapy during the first trimester, when the developing fetus is most susceptible to adverse effects of drug exposure. Although most HIV transmission is thought to occur during late pregnancy or delivery, this recommendation is not well supported by data.

In the present study, Luisa Galli and colleagues used logistic regression models to estimate adjusted odds ratios for factors potentially contributing to mother-to-child transmission, including maternal ART interruption, in a prospective cohort of pediatric patients in the Italian Register for HIV Infection in Children.

Results

• Among 937 pregnant HIV positive women, 81 (8.6%) interrupted ART during the first trimester and 11 (1.2%) did so during the third trimester.
• During the first trimester, the median time of ART interruption was 6 weeks gestation, and the median time without treatment was 8 weeks.
• During the third trimester, the median time of ART suspension was 32 weeks gestation and the median time off treatment was 6 weeks.
• Plasma HIV viral load was similar in women who interrupted treatment during the first trimester and those who did not stop therapy.
• Overall, the rate of mother-to-child HIV transmission in the entire cohort was 1.3%.
• However, the transmission rate was higher when ART was interrupted, 4.9% if stopped during the first trimester and 18.2% if stopped during the third trimester.
• In the multiple logistic regression models, only the following factors were independently associated with an increased risk of mother-to-child HIV transmission:
• Interruption of ART during either the first or third trimester;
• Maternal use of antiretroviral monotherapy or dual therapy, as opposed to a complete regimen of at least 3 drugs;
• Delivery by a method other than elective cesarean section (i.e., vaginal birth or emergency cesarean);
• Delivery when HIV RNA was greater than 4.78 log10 copies/mL.

Based on these results, the study authors concluded, "Discontinuing ART during pregnancy increases the rate of mother-to-child transmission of HIV-1, either when ART is stopped in the first trimester and subsequently restarted or when it is interrupted in the third trimester."

"This finding supports recommendations to continue ART in pregnant women who are already receiving treatment for their health," they added.

The results are also compatible with the U.S. recommendation that untreated HIV positive women start combination ART during pregnancy even if they don't yet need treatment for their own health.

University of Florence and Centre for the Study and Prevention of Tumours, Research Institute of the Tuscany Region, Florence; University of Turin, Turin; Mangiagalli Hospital; University of Milan, Sacco Hospital and S. Paolo Hospital, Milan; University of Padua, Padua; Gemelli Hospital, Spallanzani Hospital and Bambino Gesù Children's Hospital, Rome; University of Brescia, Brescia; Federico II University, Naples; University of Pavia, Pavia; University of Modena, Modena; Hospital of Bergamo, Bergamo University of Bari, Bari, Italy.

3/27/09

Reference

L Galli, D Puliti, E Chiappini, and others.Is the Interruption of Antiretroviral Treatment During Pregnancy an Additional Major Risk Factor for Mother-to-Child Transmission of HIV Type 1? Clinical Infectious Diseases. March 23, 2009 (Epub ahead of print). (Abstract).

Antiretroviral Therapy during Pregnancy Significantly Reduces Mother-to-child HIV Transmission, but is Linked to Low Birth Weight

Since the mid-1990s, it has been known that prophylactic use of certain antiretroviral drugs during pregnancy -- namely zidovudine (AZT; Retrovir) and nevirapine (Viramune) -- dramatically reduces the risk of mother-to-child HIV transmission. However, outcomes in women who use triple combination antiretroviral therapy during pregnancy are less well characterized.

In a report published in the September 12, 2008 issue of AIDS, researchers with the French/African Ditrame Plus and MTCT-Plus Projects studied pregnancy outcomes in 326 HIV-1-infected pregnant women receiving antiretroviral therapy in Abidjan, Cote d'Ivoire.

Between March 2001 and July 2003, HAART was not yet available, and women who would have been eligible for combination therapy based on their own disease status instead received a short-course of zidovudine (with or without lamivudine) plus a single dose of nevirapine during labor to prevent mother-to-child transmission (PMTCT group; n = 175). Between August 2003 and August 2007, women eligible for HAART received combination therapy (HAART group; n = 151). All infants received zidovudine and nevirapine after birth, and women were advised to either feed formula or exclusively breast-feed (shown to be safer than mixed feeding of breast milk plus other foods). Median CD4 cell counts were similar in the 2 groups (177 vs 182 cells/mm3, respectively).

The researchers recorded the frequencies of low birth weight (<2500 g), very low birth weight (below 2000 g), stillbirth, and infant mortality within the first year. Risk factors associated with low birth weight were investigated using a logistic regression model.

Results

• At 12 months, 3 infants (2.3%) became infected with HIV in the HAART group compared with 25 infants (16.1%) in the PMTCT group (P < 0.001).

• The rate of very low birth weight was similar in the 2 groups.

• The rate of low birth weight was nearly twice as high in HAART group compared with the PMTCT group (22.3% vs 12.4%; P = 0.02).

• In a multivariable analysis, after adjusting for maternal CD4 count, WHO disease stage, age, and body mass index (BMI), the following factors were significantly associated with low birth weight:

• HAART initiated before pregnancy (adjusted odds ratio [AOR] 2.88);

• HAART started during pregnancy (AOR 2.12);

• Low maternal BMI at the time of delivery (AOR 2.43).

• The rate of stillbirth was similar in both groups, at about 3%.

• The overall infant mortality rate during the first year was about 7%.

• Low birth weight and HAART use were not associated with a greater risk of infant death, though being HIV infected led to greater mortality.

Based on these findings, the study authors concluded that "HAART in pregnant African women with advanced HIV disease substantially reduced mother-to-child transmission, but was associated with low birth weight."

HIV transmission is less likely to occur when viral load is fully suppressed, and mothers are more likely to achieve undetectable viral load with combination HAART than with only zidovudine/nevirapine.

Given the highly significant reduction in the rate of HIV infection in babies born to women on HAART, and given that low birth weight infants were not more likely to die, this study indicates that the benefits of HAART for pregnant women outweigh the risks.

9/23/08

Reference

DK Ekouevi, PA Coffie, R Becquet, and others. Antiretroviral therapy in pregnant women with advanced HIV disease and pregnancy outcomes in Abidjan, Côte d'Ivoire. AIDS 22(14): 1815-1820. September 12, 2008 (Abstract).