Implementation and Assessment of a Medication Therapy Management Program in HIV Patients at High Risk of Adverse Drug Events at Khartoum, Sudan

This three-arm, parallel-group, open-label randomized controlled trial evaluates the effectiveness and cost-effectiveness of two levels of pharmacist-led Medication Therapy Management (MTM), Basic MTM and Enhanced MTM, compared with usual care among HIV patients at high risk of adverse drug events in Khartoum, Sudan. The study also includes an implementation evaluation guided by the Consolidated Framework for Implementation Research (CFIR).

Participants are randomly assigned in a 1:1:1 ratio to one of three study arms using a computer-generated random sequence prepared by an independent statistician. Randomization is performed using variable block sizes and is stratified by study site and baseline viral suppression status. Allocation concealment is maintained using sequentially numbered, sealed, opaque envelopes opened only after completion of baseline assessments.

Because of the nature of the MTM intervention, participants and pharmacist investigators are not blinded to treatment allocation. Laboratory personnel responsible for viral load and CD4 measurements and the independent statistician performing the primary analyses remain blinded to treatment allocation.

The primary analysis follows the intention-to-treat principle and includes all randomized participants. Missing outcome data are handled using multiple imputation by chained equations (MICE). A prespecified per-protocol sensitivity analysis includes participants who complete at least 80% of scheduled MTM visits and have complete outcome data. Primary and secondary outcomes are assessed over a 24-month follow-up period using appropriate statistical methods specified in the study protocol.

The study includes clinical, patient-reported, economic, and implementation outcomes, including medication adherence, viral load suppression, CD4+ cell count, adverse drug events, drug-related problems, health-related quality of life, treatment self-efficacy, patient satisfaction, and cost-effectiveness.

Study oversight is provided by the Trial Steering Committee, which reviews study progress and data annually. No formal interim analyses or stopping rules are planned because the study evaluates a low-risk pharmacist-led behavioral intervention. Any protocol deviations are documented and managed according to the study protocol.

Inclusion criteria

Participants must meet all of the following criteria:

Age: ≥18 years at the time of enrollment. HIV Status: Laboratory-confirmed HIV infection. ART Duration: Receiving antiretroviral therapy (ART) for at least 3 months prior to enrollment.

Language and Consent: Able to communicate in Arabic or English and willing and able to provide written informed consent.

High-Risk Status: Meeting at least 2 of the following high-risk criteria:

Receiving ≥8 chronic medications, including ART and medications for comorbidities.

Having ≥3 chronic comorbidities (e.g., diabetes mellitus, hypertension, hepatitis, or tuberculosis).

Documented or self-reported adverse drug event within the previous 12 months. Viral load >200 copies/mL during the previous 6 months. Self-reported medication adherence <95% or repeated missed clinic appointments. Attendance at the participating HIV clinic on at least 2 occasions during the assessment period.

Exclusion criteria

Participants will be excluded if they meet any of the following criteria:

Age <18 years. Pregnancy. Significant cognitive impairment preventing informed consent or study participation.

Terminal illness with expected life expectancy <12 months. Concurrent participation in another pharmacological intervention study. Previous participation in a formal Medication Therapy Management (MTM) program within the past year.

Planned relocation away from Khartoum State during the follow-up period. Inability to provide informed consent for any reason.