Cumulative effect of cotrimoxazole, isoniazid and opportunistic infection prophylaxis on CD4 response among people living with HIV on first-line ART in Ari Zone, Southern Ethiopia

Abstract Background Prophylactic medications are commonly used to prevent tuberculosis and opportunistic infections in people living with HIV (PLWH) who are on first-line antiretroviral therapy (ART). However, their cumulative influence on cluster of differentiation 4 (CD4) responses is still a subject of ongoing investigation. Methods A retrospective chart review was conducted utilizing secondary data derived from medical records of 500 people living with HIV (≥ 15 years) who initiated first-line ART at Jinka General Hospital in Ari Zone, South Ethiopia, between September 2019 and January 2025. CD4 response was defined as an increase of ≥ 50 cells/µL from baseline to the most recent measurement. The most recent CD4 measurement taken up to January 2025 was used for analysis. The primary outcome measure was a binary variable for CD4 response, defined as an increase of ≥ 50 cells/µL from baseline to end-line counts. Multivariable binary logistic regression was used to assess independent and interaction effects of prophylactic therapies on CD4 response. Results Among 500 participants, 50.2% demonstrated an improvement in CD4 count. Use of cotrimoxazole preventive therapy (CPT), isoniazid preventive therapy (IPT), and opportunistic infection (OI) medications was each independently associated with higher odds of CD4 improvement. However, interaction analysis showed that the CPT-OI combination and the triple CPT-IPT-OI regimen showed a statistically significant interaction suggesting a possible synergistic association with CD4 recovery beyond their individual additive effects. Predicted probabilities of CD4 improvement increased progressively with dual and triple prophylactic combinations compared with no prophylaxis. Conclusion The combined use of prophylactic medications was significantly associated with CD4 recovery in people living with HIV on first-line ART. These findings emphasize the importance of integrated preventative strategies, particularly in resource-limited settings, and highlight the need for adherence support among individuals with limited formal education and those living in rural areas. The study’s generalizability is limited, however, due to its single-center retrospective design and the use of a broad category for “OI prophylaxis” without specifying individual drugs.