The purpose of this study is to interpretively analyse the fight against HIV/AIDS, referred to as ‘response’, in three of Lesotho’s institutions of higher education (IHEs). These are the Lesotho College of Education (LCE), the National Health Training College (NHTC) and the National University of Lesotho (NUL). This study uses cultural historical activity theory (CHAT) to qualitatively interpret the response in a country with the second highest HIV prevalence globally. The study applies Vygotsky’s first generation of CHAT, Leontiev’s multifaceted second generation, and Engeström’s third generation, which features a minimum of two interacting activity systems. Its multimodal methodology draws from Mukeredzi’s (2009, p.56) critique of CHAT and its problem of not getting “in” deep into dimensions of an activity. Thus, this study incorporates closely matching theories, models and concepts around CHAT; mainly the World Health Organisation’s (2004b) health standards, Zeithaml and Bitner’s (2000) services marketing mix and Checkland and Holwell’s (1998) information systems. The findings reveal that conceptual tools - human skills and policies, do not mediate material processes such as planning, financing and reporting, resulting in a poor response. Gaps in human agency across critical elements of activity in the three IHEs result in conceptual, functional and material contradictions, and poor use of mediating artefacts adversely affects all interventions, including HIV testing and services (HTS), anti-retroviral (ARV) treatment and viral load suppression (VLS) envisaged in the UNAIDS (2014a and 2015) guidelines. This study teased out ‘expanded contradictions’ and tensions in the IHEs response, which invoked expansion, transformations, opportunities and new implications. Despite the IHEs leadership awareness of need for change, an historical embeddedness in unchanging cultures and functional contradictions due to poor agency (by subjects), lack of policies (rules), finance, (tools), hamper the response. The study found opportunities for IHEs against HIV/AIDS. Thisstudy recommends two new agency models. One is ‘knit-working’, which aims to improve responses by identifying key, specific, and rapidly doable ‘nitty-gritty’ inter-college activities. The second model aims to strengthen IHEs leadership agency through 3-Cs of commitment at top management, improved resources and capacity at middle management, in order to enable operational level services to evidence the concern over AIDS. This study will alleviate a dearth of literature in the nexus of Lesotho’s IHEs, HIV/AIDS and services.