This dissertation sets out to explore how two Ugandan NGOs, the Straight Talk Foundation and the Family Planning Association of Uganda have responded to and negotiated with the President’s Emergency Plan for AIDS Relief (PEPFAR). Ascertaining a conflictual relation between the rights-based approach to HIV prevention for young people of the two NGO and the value-based approach by PEPFAR, it is demonstrated that this contradiction can to some degree be prevailed over through negotiation, assimilation and contestation of donor conditionalities in the practical implementation of projects. But from the perception of the two NGOs, PEPFAR has also intensified the antagonisms in Uganda over which HIV prevention method is appropriate for young people. This is evident in how PEPFAR has strengthened and coordinated faith-based voices and prominent public individuals in opposing condom use, to the effect of consolidating the prevailing power structures claim to define an appropriate ‘African’ sexual conduct in opposition to national policies on HIV prevention for young people. Despite several conducive factors for the rights-based agendas of the two NGOs, they have faced considerable opposition in navigating and manoeuvring this PEPFAR environment, in which their integration into the political system has restricted them from challenging an emerging hegemony of abstinence-only among Ugandan HIV/AIDS stakeholder. This has had the effect of restraining the rights based HIV prevention activities of the two NGOs, as well as their aspired integration of HIV prevention with comprehensive reproductive health interventions, just as it has marginalised sexual and reproductive health and rights considerations in Ugandan HIV/AIDS efforts. This decreased attention to reproductive health and rights-based HIV prevention is further intensified by the earmarking of foreign aid to exclusively target HIV/AIDS, just as Uganda’s reliance on foreign aid impose a pursuit for ‘sound economics’ that are detrimental to the implementation of national health priorities. PEPFAR’s advancement of a value-based approach to HIV prevention is thus reflective of an overall penetration of foreign aid into African states, and the reduced autonomy of African governance structures which this donor dependency results in, revealing the deeply political-economical character of any response and attempt to stem the HIV/AIDS epidemic.