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The impact of screening and treating AUD and MDD on HIV outcomes is unknown. We aimed to identify the cost-effectiveness of AUD and MDD interventions in Zimbabwe, and their potential contribution to reaching Zimbabwe\u2019s Ending the HIV Epidemic 2030 goal.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using a validated HIV compartmental transmission model in Zimbabwe, we compared four policy scenarios: prevention as usual (baseline); implement AUD screening (using AUDIT) and treatment (motivational interviewing and cognitive-behavioral therapy); implement MDD screening (using PHQ-9) and treatment (cognitive-behavioral therapy); and implement screening and treatment for both. Outcomes were HIV incidence projections, infections averted through 2030, quality-adjusted life-years gained, cost per infection averted, and cost per QALY gained. Analyses considered \u201cspillover,\u201d when treatment for AUD also results in an improvement in MDD and the converse. Sensitivity analyses identified cost reductions necessary for AUD and MDD interventions to be as cost-effective as other HIV interventions, particularly the scale-up of long-acting PrEP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>AUD and MDD combined will be responsible for 21.1% of new HIV infections in Zimbabwe by 2030.<jats:italic>Without considering spillover<\/jats:italic>, compared to the baseline, MDD intervention can reduce new infections by 5.4% at $2039\/infection averted and $3186\/QALY. AUD intervention can reduce new infections by 5.8%, but at $2,968\/infection averted and $4753\/QALY, compared to baseline. Both MDD and AUD interventions can reduce new infections by 11.1% at $2810\/infection averted and $4229\/QALY, compared to baseline.<jats:italic>Considering spillover<\/jats:italic>, compared to the baseline, MDD intervention can reduce new infections by 6.4% at $1714\/infection averted and $2630\/QALY. AUD intervention can reduce new infections by 7.4%, but at $2299\/infection averted and $3560\/QALY compared to baseline. Both MDD and AUD interventions can reduce new infections by 11.9% at $2247\/infection averted and $3382\/QALY compared to baseline. For MDD intervention to match the cost-effectiveness of scaling long-acting PrEP, the cost of MDD intervention would need to be reduced from $16.64 to $12.88 per person.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Implementing AUD and MDD interventions can play an important role in HIV reduction in Zimbabwe, particularly if intervention cost can be decreased while preserving effectiveness.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12916-024-03674-8","type":"journal-article","created":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T00:02:07Z","timestamp":1729468927000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Cost-effectiveness of screening and treating alcohol use and depression among people living with HIV in Zimbabwe: a mathematical modeling study"],"prefix":"10.1186","volume":"22","author":[{"given":"Jasmine I-Shin","family":"Su","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao-rui","family":"Yeo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mellesia","family":"Jeetoo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neo K.","family":"Morojele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel M.","family":"Francis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheela","family":"Shenoi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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