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Background: HIV and sub-optimal infant feeding practices remain important threats to child growth, development, and survival in low- and middle-income countries. To our knowledge, few studies have explored health service users' perspective of infant feeding in the context of WHO Option B+ policy to prevent vertical HIV transmission (PMTCT). This paper is a sub-analysis of qualitative data from a mixed-methods multi-level process evaluation of Option B+ implementation in South Africa (SA). In this study we explored health facility users' infant feeding knowledge, perceptions, and practices one year after SA adopted the 2016 updated World Health Organization prevention of mother-to-child transmission of HIV Option B+ infant feeding guidelines. Methods: Nineteen focus group discussions (FGDs) were held with six groups of men and women whose infants were aged < 6 months. Participants were attending randomly selected primary health care facilities within six purposively selected priority districts. The six groups included in the FGDs were: (i) adolescent girls and young women living with HIV (WHIV), (ii) adolescent girls and young women not living with HIV (WNHIV), (iii) older postnatal WHIV (iv) older postnatal WNHIV (v) pregnant women, and (vi) men. Data collection took place between April and December 2018. Data analysis involved coding and thematic framework analysis. Results: Women and men have suboptimal knowledge of the recommended breastfeeding duration and exclusive breastfeeding, especially for HIV-exposed infants. Most women received sub-optimal infant feeding counselling and mixed messages from health care workers. Fewer WHIV initiated breastfeeding at birth compared to WNHIV. Most parents believed that HIV-exposed infants should be breastfed for 6 months and many postnatal women on antiretroviral drugs and younger mothers lacked confidence to breastfeed beyond 6 months. Mixed feeding was predominant among all women due to individual, family, and socio-structural barriers. Many men were supportive on infant feeding; however, they lacked the appropriate information and skills to influence their partners' infant feeding decisions. Conclusions: Differences in breastfeeding practices between WHIV and WNHIV are highly influenced by the lack of knowledge of infant feeding policy recommendations. Multiple-level factors deter many mothers from adhering to recommended guidelines. Appropriate ongoing infant feeding counselling and breastfeeding support are required for women and their partners. [ABSTRACT FROM AUTHOR]