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Interrupting Mother-to-Infant Transmission of HIV

Studies conducted in Thailand and Malawi suggest that low-cost pre- and perinatal antiviral prophylaxis can reduce mother-to-infant HIV transmission.

Landmark studies demonstrated that reducing maternal viral load with zidovudine (ZDV) significantly decreased mother-to-infant HIV transmission. In subsequent trials, more-intensive treatment of mothers further reduced transmission rates, to 2%. Unfortunately, such regimens are too expensive and complex for use in developing countries. Three new reports detail efforts to develop effective, less expensive regimens.

Lallemant and colleagues, partially supported by industry, conducted a randomized, double-blind, placebo-controlled study involving HIV-infected pregnant women in Thailand who were receiving ZDV starting in the third trimester. The researchers assessed whether adding single doses of nevirapine (NVP), given to mothers at the onset of labor or to both mothers and newborn infants, would further reduce HIV transmission. All infants received 1 week of ZDV and were formula-fed. Over 2 years, 1844 women were enrolled. After an early analysis showed a transmission rate of 6.3% for the group in which neither mother nor infant received NVP (vs. 1.1% for the group in which both mother and infant received NVP), that arm was discontinued, and all women received NVP. In the final per-protocol analysis, similar rates of transmission were seen for the group in which both mother and infant received NVP (1.9%) and the group in which only the mother received it (2.8%).

Taha and colleagues performed a randomized, open-label study in Malawi among 894 HIV-infected mothers receiving intrapartum NVP and their infants, who were given one dose of NVP at birth, to determine whether administering ZDV for 1 week to the infants would reduce the HIV transmission rate. Nearly all infants were breast-fed. Among those who were HIV-negative at birth, frequency of infection at 6 to 8 weeks was similar between groups. However, infants of mothers with HIV viral loads 100,000 copies/mL had approximately double the infection rate of infants with mothers having <100,000 copies/mL.

Resistance mutations to nonnucleoside reverse-transcriptase inhibitors (NNRTIs) have been found in 15% to 40% of mothers receiving NVP prophylaxis during labor; such prophylaxis could therefore decrease the effectiveness of subsequent antiretroviral treatment. Jourdain and colleagues examined the clinical effect of NVP resistance in 269 women from the Thai study who had CD4 counts <250 cells/mm³ (221 who received NVP during labor and 48 who did not). HIV genotyping of blood samples obtained 10 days postpartum revealed one or more NNRTI resistance mutations among 32% of women receiving NVP prophylaxis but no mutations among those not receiving NVP. The women were treated with NVP-containing highly active retroviral therapy (HAART). Six months after HAART initiation, HIV viral loads were <50 copies/mL in 49% of women with and 68% of women without NVP exposure during labor (P=0.03). Among intrapartum NVP recipients, viral suppression was achieved in 38% of those with resistance mutations and 52% of those without mutations (P=0.08). Virologic failure was independently associated with higher viral load at HAART initiation and with receipt of NVP during labor.

Comment: The mothers in Malawi, unlike those in Thailand, were not already receiving ZDV, and most had their HIV infection diagnosed during labor. Furthermore, in Malawi, nearly all infants were breast-fed -- a risk factor for HIV transmission.

The good news is that when HIV-infected pregnant women receive third-trimester ZDV therapy, a single intrapartum dose of NVP further reduces HIV transmission. An additional infant dose may slightly increase this benefit. However, two patients' well-being must be considered. Decisions regarding pre- and perinatal prophylaxis must balance minimizing the risk of mother-to-infant HIV transmission against the risk of compromising the mothers' future response to HAART.

— Robert S. Baltimore, MD

Published in Journal Watch Infectious Diseases August 23, 2004

Citation(s):

Lallemant M et al. Single-dose perinatal nevirapine plus standard zidovudine to prevent mother-to-child transmission of HIV-1 in Thailand. N Engl J Med 2004 Jul 15; 351:217-28.

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Taha TE et al. Nevirapine and zidovudine at birth to reduce perinatal transmission of HIV in an African setting: A randomized controlled trial. JAMA 2004 Jul 14; 292:202-9.

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Jourdain G et al. Intrapartum exposure to nevirapine and subsequent maternal responses to nevirapine-based antiretroviral therapy. N Engl J Med 2004 Jul 15; 351:229-40.

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• Medline abstract (Free)