Further evidence to support Option B+: good HIV-free survival among children breastfed for a year with mothers on triple ART

Early infant feeding patterns and HIV-free survival: findings from the Kesho-Bora trial (Burkina Faso, Kenya, South Africa).

Cournil A, Van de Perre P, Cames C, de Vincenzi I, Read JS, Luchters S, Meda N, Naidu K, Newell ML, Bork K, Kesho Bora Study G. Pediatr Infect Dis J. 2015 Feb;34(2):168-74. doi: 10.1097/INF.0000000000000512.

Objective: To investigate the association between feeding patterns and HIV-free survival in children born to HIV-infected mothers and to clarify whether antiretroviral (ARV) prophylaxis modifies the association.

Methods: From June 2005 to August 2008, HIV-infected pregnant women were counseled regarding infant feeding options, and randomly assigned to triple-ARV prophylaxis (triple ARV) until breastfeeding cessation (BFC) before age 6 months or antenatal zidovudine with single-dose nevirapine (short-course ARV). Eighteen-month HIV-free survival of infants HIV-negative at 2 weeks of age was assessed by feeding patterns (replacement feeding from birth, BFC <3 months, BFC ≥3 months).

Results: Of the 753 infants alive and HIV-negative at 2 weeks, 28 acquired infection and 47 died by 18 months. Overall HIV-free survival at 18 months was 0.91 [95% confidence interval (CI): 0.88-0.93]. In the short-course ARV arm, HIV-free survival (0.88; CI: 0.84-0.91) did not differ by feeding patterns. In the triple ARV arm, overall HIV-free survival was 0.93 (CI: 0.90-0.95) and BFC <3 months was associated with lower HIV-free survival than BFC ≥3 months (adjusted hazard ratio: 0.36; CI: 0.15-0.83) and replacement feeding (adjusted hazard ratio: 0.20; CI: 0.04-0.94). In the triple ARV arm, 4 of 9 transmissions occurred after reported BFC (and 5 of 19 in the short-course arm), indicating that some women continued breastfeeding after interruption of ARV prophylaxis.

Conclusions: In resource-constrained settings, early weaning has previously been associated with higher infant mortality. We show that, even with maternal triple-ARV prophylaxis during breastfeeding, early weaning remains associated with lower HIV-free survival, driven in particular by increased mortality.

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Editor’s notes: Evaluating the impact of feeding patterns on infant HIV-free survival is essential for HIV prevention. This large, multi-country study was nested within the Kesha Bora randomised trial which found that triple ARV prophylaxis until cessation of breastfeeding was associated with lower rates of mother-to-child transmission than short-course ARV prophylaxis. Further analyses showed that in both arms, mortality in infants was highest when breastfeeding was stopped before three months of age. This analysis considered HIV-free survival and found that among mothers receiving triple ARV prophylaxis during breastfeeding, weaning before three months was associated with significantly lower HIV-free survival than longer breastfeeding or replacement feeding from birth. Overall, the results support the WHO 2013 ART guidelines which recommend initiation of triple ARV prophylaxis early in pregnancy, continued either through the breast feeding period (option B) or for life (option B+), and WHO recommendations for continued breastfeeding up to at least one year of age while on ART. 

Burkina Faso, Kenya, South Africa
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