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In 2018, 18.8 million women were living with human immunodeficiency virus (HIV) and accounted for 52% of persons living with HIV worldwide. Despite exceptional gains made in reducing the HIV burden, women remain underrepresented and underserved. As we move toward ending the global HIV epidemic, key issues which impact women’s risk for acquiring HIV and the barriers which may prevent effective epidemic control in women will have to be addressed. The risks of women as receptive sex partners, the scarcity of HIV prevention options for women and pregnancy concerns require specific attention. Additionally, as the projected life-spans of women living with HIV increases, our focus must also expand to those issues specific to the aging woman. We must aim to reduce comorbidities and address unintended medication induced effects. To reach and sustain global control of HIV, psychological well-being and the quality of life of women living with HIV should be prioritized. This report investigates a few of the biological, psychological and scientific issues surrounding women which challenge the feasibility and sustainability of an end to the HIV epidemic.