Introduction: Serodiscordance where one partner in a couple is HIV-positive and the other is HIV-negative—poses a major challenge in the fight against HIV/AIDS, particularly in sub-Saharan Africa. Despite its epidemiological relevance, little is known about this phenomenon in Lubumbashi, Democratic Republic of the Congo (DRC). Methods: A cross-sectional study was conducted from January 15 to March 31, 2025 at the Lubumbashi Center of Excellence for HIV/AIDS. A total of 132 couples were enrolled. Data were collected using structured questionnaires, validated scales (HSS-10 for stigma, MOS for social support), and medical records. Statistical analysis was performed using Jamovi software (version 2.4). Results: Serodiscordance prevalence was 68.2%. Pre-exposure prophylaxis (PrEP) was used by only 8.3% of participants, and consistent condom use was reported by 14.4%. High perceived stigma was associated with a 40% decrease in antiretroviral adherence (OR = 0.60; p < 0.01). Higher education and strong social support were positively associated with the use of prevention tools. Factors associated with the use of prevention tools were a secondary or higher education level (OR = 2.10; 95% CI: 1.15 - 3.82), high social support (OR = 1.75; 95% CI: 1.02 - 3.01) and a low level of stigmatization (OR = 0.60; 95% CI: 0.42 - 0.85). Conclusion: Serodiscordant couples are highly prevalent in Lubumbashi but remain underserved. Social stigma, lack of education, and structural barriers limit the effectiveness of biomedical prevention strategies. Community-based interventions and improved access to HIV prevention tools are urgently needed.
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