Abstract Background HIV-negative members of sero-discordant couples are at high risk for HIV acquisition but few behavioral prevention interventions have been implemented in sub-Saharan Africa and discordance is not well understood by couples themselves. Methods In this nested sub-study, we interviewed 40 HIV sero-discordant couples before and after a 6-month behavioral intervention that was comprised of four group discussions on specific HIV prevention and care topics. The content of the sessions included: 1) understanding HIV serodiscordance and reducing risk, 2) couple communication, 3) reproductive health and HIV serodiscordance, 4) coping with HIV serodiscordance and ongoing support. Couple members were interviewed individually. Data were analyzed thematically using ‘Framework Analysis’ which incorporated dyadic factors to address couple issues. Results Analysis revealed pre-identified concepts and emergent themes that were relevant to the final conceptual model. Four major categories of factors affecting couple relations, beliefs and current risk behaviors emerged: intervention factors, structural/contextual factors, physical health factors, and past risk behavior. The topics within the intervention most relevant were communication and reproductive health. The contextual factors highlighted by couples were gender norms around sexual decision-making and multiple partnerships. Individual beliefs regarding HIV serodiscordance persisted over all time points for some couples. Interestingly, some couple members had divergent views about their HIV status; some believing the HIV-negative member was negative while others described multiple beliefs around the negative member’s blood surely being positive for HIV. Couple communication emerged as an important theme mediating beliefs and behavior. Conclusions In addition to biomedical and behavioral interventions, HIV-serodiscordant couple interventions must embrace the contextual complexity and cultural understanding of HIV infection and discordance as well as the dynamic nature of couple communication to influence risk behavior.