The importance of continued infant prophylaxis against HIV-1 transmission throughout breastfeeding

Efficacy and safety of an extended nevirapine regimen in infants of breastfeeding mothers with HIV-1 infection for prevention of HIV-1 transmission (HPTN 046): 18-month results of a randomized, double-blind, placebo-controlled trial.

Fowler MG, Coovadia H, Herron CM, Maldonado Y, Chipato T, Moodley D, Musoke P, Aizire J, Manji K, Stranix-Chibanda L, Fawzi W, Chetty V, Msweli L, Kisenge R, Brown E, Mwatha A, Eshleman SH, Richardson P, Allen M, George K, Andrew P, Zwerski S, Mofenson LM, Jackson JB; for the HPTN 046 Protocol Team. J Acquir Immune Defic Syndr. 2013 Nov 1. [Epub ahead of print]

Background: HPTN 046 compared the efficacy and safety of infant nevirapine (NVP) among HIV-exposed breastfed infants randomized at 6 weeks to 6 months to NVP or placebo to prevent postnatal infection: we report final 18 month outcomes.

Methods: Randomized, placebo-controlled trial in four African countries. Infant diagnostic HIV testing was done regularly from birth, through 18 months. Kaplan-Meier analysis was used to assess 18 month cumulative infant HIV infection, HIV infection/or death and mortality rates.

Results: Between 6 weeks and 6 months, postnatal HIV infection rates were significantly lower, among infants receiving daily NVP from 6 weeks to 6 months 1.1% (95% CI 0.2-1.8%), compared to placebo: 2.4% (95% CI 1.3-2.6%), p=0.049; but not significantly lower thereafter. Eighteen month postnatal infection rates were low: 2.2% [95% CI 1.1-3.3%] versus 3.1% [95% CI 1.9-4.4%], respectively, p=0.28. Mortality and HIV infection/death did not differ between arms at any age. Infants of women receiving antiretroviral therapy (ART) for their own health had the lowest 18 month postnatal infection rates (0.5%, 95% CI 0.0-1.1%). However, HIV infection/death rates at 18 months were not significantly different for infants of mothers on ART (3.7%, 95% CI 1.9-5.5%); and infants of mothers with CD4 >350/mm not receiving ART (4.8%, 95% CI 2.7-6.8%), (p=0.46). There were no differences in adverse events between study arms.

Conclusion: This trial demonstrated early but not late differences in postnatal HIV transmission among infants randomized at age six weeks to extended NVP or placebo, underscoring the importance of continued prophylaxis throughout breastfeeding.

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Editor’s notes: Despite increased coverage of antiretroviral treatment for pregnant women living with HIV, approximately 230 000 children are newly infected with HIV each year. The HPTN046 trial was designed to test the efficacy and safety of extended once daily infant nevirapine (NVP) prophylaxis to six months, among breastfed, HIV exposed infants who had received 6 weeks of NVP and were uninfected at age 6 weeks.  The trial was implemented at a time when breastfeeding was recommended to stop by 6 months for HIV exposed infants. This paper reports final HIV transmission, infant HIV-free survival and overall infant survival through to 18 months of age. Disappointingly, there was little evidence of a difference in postnatal HIV transmission rates between study arms (cumulative 18 month HIV-free survival rate of 94.5% in the NVP arm versus 93.3% in the placebo arm; p=0.32) and similar infant survival rates (95.3% versus 95.9%; p=0.72). The results of the 6 month follow-up, and the low transmission rate among infants whose mothers were on ART throughout 18 month follow-up emphasize the importance of ART provision to mothers who require it for their own health, and infant prophylaxis during the breastfeeding period (now recommended as 12 months). 

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