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Oral Antiretrovirals Protect Infants from HIV Infection During Breast-Feeding

Infants born to HIV-positive mothers were less likely to become infected during their first year after birth if they received pre-exposure prophylaxis (PrEP) using liquid formulations of lamivudine or lopinavir/ritonavir while breast-feeding, according to a study from Africa published in the November 18, 2015 edition of The Lancet.

Though the term "PrEP" is typically used to refer to use of Truvada (tenofovir/emtricitabine) to prevent sexual transmission of HIV, the first proof-of-concept was using early antiretrovirals like zidovudine (AZT or Retrovir) to prevent vertical transmission from HIV-positive mothers to their infants during pregnancy or delivery.

Giving babies antiretrovirals after birth may also help prevent HIV transmission during breast-feeding -- an important consideration in areas were clean water and safe formula are not widely available. But so far strategies to prevent post-natal mother-to-child transmission have not been assessed for longer than 6 months of breast-feeding, which is recommended for up to a year.

Nicolas Nagot from Université Montpellier in France and colleagues compared the safety and efficacy of infant prophylaxis using 2 antiretroviral monotherapy regimens -- lamivudine (3TC or Epivir, which is similar to the tenofovir in Truvada) or ritonavir-boosted lopinavir (Kaletra) -- to prevent post-natal HIV transmission during up to 50 weeks of breast-feeding.

This double-blind, randomized controlled trial enrolled 1273 HIV-uninfected infants born to HIV-positive women at 4 sites in Burkina Faso, South Africa, Uganda, and Zambia between November 2009 and May 2012. The mothers had CD4 T-cell counts above 350 cells/mm³ and therefore were not eligible for antiretroviral therapy (ART) according to treatment guidelines in effect at the time (now the World Health Organization recommends that all people living with HIV should receive ART).

At 7 days after birth the infants were randomly assigned to start liquid formulations of either lamivudine or lopinavir/ritonavir twice-daily, continuing through 1 week after the complete cessation of breast-feeding or at the final study visit at week 50. Mothers were counseled to breast-feeding exclusively during the first 6 months, gradually introduce other foods, and stop breast-feeding completely by 50 weeks. The final analysis included 621 babies assigned to lamivudine and 615 assigned to lopinavir/ritonavir.

Results

• Overall, there were 17 new HIV infections diagnosed during the follow-up period: 9 in the lamivudine group and 8 in the lopinavir/ritonavir group.
• Infection rates did not differ significantly between the 2 drug regimens (hazard ratio 0.90 comparing lopinavir/ritonavir vs lamivudine; p=0.83).
• Cumulative HIV infection rates were 1.5% and 1.4% in the lamivudine and lopinavir/ritonavir groups, respectively.
• While ART adherence was high overall (93% with lamivudine and 90% with lopinavir/ritonavir), most infant infections were associated with poor adherence.
• Among babies with good adherence, infection rates fell to 0.8% in the lamivudine group and 0.2% in the lopinavir/ritonavir group, again not a significant difference.
• About half of the infections occurred during the second 6 months, as breast-feeding decreased and other foods were introduced (prior studies have also found that such mixed feeding is associated with higher HIV risk than exclusive breast-feeding).
• Severe adverse events among the infants did not differ between the treatment groups.
• 246 infants (50%) in the lamivudine group and 251 (51%) in the lopinavir/ritonavir group had grade 3-4 adverse events.
• A total of 33 infants died during follow-up, all of whom were HIV-negative, and none of the deaths were attributed to the study drugs.

"Infant HIV-1 prophylaxis with lopinavir/ritonavir was not superior to lamivudine and both drugs led to very low rates of HIV-1 postnatal transmission for up to 50 weeks of breastfeeding," the study authors concluded.

"Crucially, about half of the postnatal HIV-1 infections in both groups occurred after 6 months of breastfeeding, while HIV exposure was much reduced during this period because of mixed feeding (lowering milk intakes) and some women stopping breastfeeding before 50 weeks," they added in their discussion. "This finding justifies the extension of infant pre-exposure prophylaxis until the end of HIV exposure and the need to inform mothers about the persistent risk of transmission throughout breast-feeding to prevent them stopping giving the treatment to their babies too soon."

"Infant PrEP proved an effective and safe alternative to prevent postnatal HIV-1 transmission for mothers who are not ready or prepared to embark on long-term ART," the authors wrote. "At the population level, in countries where universal maternal ART cannot be implemented as recommended by WHO, infant PrEP with either lopinavir/ritonavir, lamivudine, or nevirapine for the whole duration of breast-feeding is also advisable."

1/12/16

References

N Nagot, C Kankasa, JK Tumwine, et al. Extended pre-exposure prophylaxis with lopinavir–ritonavir versus lamivudine to prevent HIV-1 transmission through breastfeeding up to 50 weeks in infants in Africa (ANRS 12174): a randomised controlled trial. The Lancet. November 18, 2015 (online ahead of print).

H Coovadia and D Moodley. Improving HIV pre-exposure prophylaxis for infants. The Lancet. November 18, 2015 (online ahead of print).

Other Source

The Lancet. Breastfeeding babies protected against HIV infection from their HIV-positive mothers with 12 months of liquid antiretroviral drug treatment. Press release. November 18, 2015.