Individualizing the WHO HIV and infant feeding guidelines: optimal breastfeeding duration to maximize infant HIV-free survival

Abstract

Objectives: To determine how infant feeding recommendations can maximize HIV-free survival (HFS) among HIV-exposed, uninfected African infants, balancing risks of breast milk-associated HIV infection with setting-specific risks of illness and death associated with replacement feeding.

Design: Validated mathematical model of HIV-exposed, uninfected infants, with published data from Africa.

Methods: We projected 24-month HFS using combinations of: maternal CD4, antiretroviral drug availability, and relative risk of mortality among replacement-fed compared to breastfed infants ('RR-RF', range 1.0-6.0). For each combination, we identified the 'optimal' breastfeeding duration (0-24 months) maximizing HFS. We compared HFS under an 'individualized' approach, based on the above parameters, to the WHO 'public health approach' (12 months breastfeeding for all HIV-infected women).

Results: Projected HFS was 65-93%. When the value of RR-RF is 1.0, replacement feeding from birth maximized HFS. At a commonly reported RR-RF value (2.0), optimal breastfeeding duration was 3-12 months, depending on maternal CD4 and antiretroviral drug availability. As the value of RR-RF increased, optimal breastfeeding duration increased. Compared to the public health approach, an individualized approach improved absolute HFS by less than 1% if RR-RF value was 2.0-4.0, by 3% if RR-RF value was 1.0 or 6.0, and by greater amounts if access to antiretroviral drugs was limited.

Conclusion: Tailoring breastfeeding duration to maternal CD4, antiretroviral drug availability, and local replacement feeding safety can optimize HFS among HIV-exposed infants. An individualized approach leads to moderate gains in HFS, but only when mortality risks from replacement feeding are very low or very high, or antiretroviral drug availability is limited. The WHO public health approach is beneficial in most resource-limited settings.

Figure 1. Base-case results: optimal breastfeeding duration to maximize infant 24-month HIV-free survival

For each combination of maternal CD4, ARV availability, and RR-RF, colored shading indicates the breastfeeding duration maximizing 24-month infant HIV-free survival.. RR-RF: relative risk of mortality among replacement-fed compared to breastfed infants; ARVs: antiretroviral drugs; ART: three-drug antiretroviral therapy; NVP: nevirapine; WHO A and B: World Health Organization-recommended PMTCT regimens.

Figure 2. 24-month HIV-free survival with individualized approach, compared to “public health approach” recommending 12 months of breastfeeding for all HIV-infected women

In each panel, the horizontal axis includes six values of RR-RF, ranging from 1.0 to 6.0. The vertical axis shows 24-month HIV-free survival, with shaded bars representing projections for the individualized approach and solid bars representing projections for the public health approach. Panels A and B depict scenarios in which providers counsel all HIV-infected mothers, with varying access to maternal ARVs. Panels C and D depict scenarios in which the individualized approach diverts provider resources and 25% of mothers receive no counseling, leading them to breastfeed for 24 months without ARVs (Panel C) or replacement feed from birth (Panel D). The difference in HFS between the individualized and public health approaches is shown for each RR-RF value; positive values indicate greater HFS with the individualized approach. HFS: HIV-free survival; RR-RF: relative risk of mortality among replacement-fed compared to breastfed infants; ARVs: antiretroviral drugs; m: months.