Short-Course NRTIs to Prevent Mother-to-Child HIV Transmission

Widespread use of AZT prophylaxis during pregnancy and labor has dramatically reduced the rate of mother-to-child HIV transmission, from about 25% to less than 2% in the United States, though gains have been smaller in developing countries.

Other nucleoside reverse transcriptase inhibitors (NRTIs) have also been studied for this purpose. In the June 2006 Journal of Acquired Immune Deficiency Syndromes, researchers reported on a comparative study of four different short-course NRTI regimens in a resource-limited setting.

This prospective, open-label study, conducted between May 1999 and May 2000, enrolled 373 pregnant South African women at 34 or more weeks of gestation. Participants were randomly assigned to one of four arms:

• AZT (zidovudine, Retrovir)
• d4T (stavudine, Zerit)
• ddI (didanosine, Videx)
• d4T + ddI

Medication was started during pregnancy and continued through delivery; newborn infants received the same drug or combination for six weeks. Infants were tested for HIV at birth and at 6, 12, and 24 weeks of age.

Results

• Maternal viral load levels decreased rapidly in all treatment arms.
• At week 4, the mean HIV RNA decreases were as follows:
• 1.91 log₁₀ copies/mL in the d4T + ddI group
• 1.33 log₁₀ copies/mL in the ddI group
• 1.12 log10 copies/mL in the d4T group
• 0.76 log10 copies/mL in the AZT group
• Among the 362 evaluable mother-infant pairs, the following numbers of infants contracted HIV by 24 weeks of age:
• 11 in the d4T group
• 10 in the ddI group
• 5 in the AZT group
• 4 in the d4T + ddI group
• 11 infections occurred in utero.

Conclusion

The researchers concluded that, “The abbreviated use of [NRTIs] for the prevention of mother-to-child transmission appears safe and effective.”

Although AZT reduced maternal viral load somewhat less than the other regimens in this study, it remains the standard approved therapy for the prevention of mother-to-child HIV transmission.

Although d4T + ddI was not associated with lactic acidosis or hepatic steatosis in this study, these serious adverse events have been observed in pregnant women taking this regimen, and the combination is listed as contraindicated during pregnancy in the current U.S. HIV treatment guidelines.

While NRTI monotherapy can help reduce the rate of mother-to-child transmission, pregnant women ideally should receive combination antiretroviral therapy to manage their own HIV disease and to prevent development of drug resistance.

6/23/06

Reference
G Gray, A Violari, J McIntyre, and others. Antiviral Activity of Nucleoside Analogues During Short-Course Monotherapy or Dual Therapy: Its Role in Preventing HIV Infection in Infants. Journal of Acquired Immune Deficiency Syndromes 42(2): 169-176. June 2006.