To investigate sexual behavior changes adopted by People Living with Human Immunodeficiency Virus (PLHIV) on Antiretroviral therapy (ART) in the Northern Region of Ghana. We employed a cross-sectional survey with a questionnaire to collect data from 900 clients from 9 major ART centers within the region. Chi-square and logistic regression analyses were applied to the data. More than 50% of PLHIV on ART use condoms, reduce sexual partners, practice abstinence, reduce unprotected sex with married/regular partners, and avoid casual sex. Fear of others getting to know patients' HIV-positive status (χ2 = 7.916, p = 0.005), stigma (χ2 = 5.201, p = 0.023), and fear of loss of family support (χ2 = 4.211, p = 0.040) significantly predict non-disclosure of HIV-positive status among the participants. Change in sexual behavior is influenced by the following: "to avoid spreading the disease to others" (R2 = 0.043, F (1, 898) = 40.237, p < 0.0005), "to avoid contracting other STIs" (R2 = 0.010, F (1, 898) = 8.937, p < 0.0005), "to live long" (R2 = 0.038, F (1, 898) = 35.816, p < 0.0005), "to hide HIV-positive status" (R2 = 0.038, F (1, 898) = 35.587, p < 0.0005), "to achieve good results from ART treatment" (R2 = 0.005, F (1, 898) = 4. 282, p < 0.05), and "to live a Godly life" (R2 = 0.023, F (1, 898) = 20. 880, p < 0.0005). High self-disclosure rate of HIV-positive status was identified, with participants disclosing to their spouses or parents. Reasons for disclosure and non-disclosure differed from person to person.
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