Major depressive disorder , also known as clinical depression, is a mental health condition that causes a persistently low or depressed mood and a loss of interest in activities that once brought joy. Major Depressive Disorder  is often not diagnosed or treated properly in people living with HIV . In fact, people living with HIV are two to four times more likely to have Major Depressive Disorder than the general population. The stigma around both mental health and HIV can make it harder for people to get the help they need. Studies show that 30-40% of people with Major Depressive Disorder do not respond to the first medicines they are given to treat depression, even when they take the right dose and follow all the instructions on how to take them. Similarly, about 30% of people with HIV struggle to find effective medicines for depression, which suggests that new treatment options are needed.

This study is testing whether pramipexole, a drug thought to be better than the drugs that are usually used to treat depression, could help with both Major Depressive Disorder and HIV-1-associated neurocognitive disorders HIV-1-associated neurocognitive disorders  in people with HIV. Escitalopram, a common antidepressant, will be used as the comparison treatment.

This study is a Phase II clinical trial (study done to evaluate the effectiveness and safety of a new drug), which will compare pramipexole extended release (ER) to escitalopram in treating Major Depressive Disorder and mild cognitive problems in people with HIV. The study will run for 24 weeks and include 186 participants globally, with 93 people in each treatment group. Participants must be 18-70 years old, on HIV treatment for at least 3 months, and have a stable HIV viral load (number of HIV viruses per milliliter of blood) of less than 200 copies/ml. At the KEMRI/WRP clinic in Kericho, 100 people will be screened, and 50 will be selected to join the study. Participants will be randomly assigned to one of two treatment groups: pramipexole  (which will be increased up to 4.5 mg per day) or escitalopram (which will be increased up to 20 mg per day), depending on how well they tolerate the medications. Approval for conduct of the study shall be obtained from KEMRI SERU, PPB and NACOSTI. Administrative review will be conducted by WRAIR Human Subjects Protection Branch (HSPB).

The results of this study are expected to help improve and guide how depression and related mental health problems are treated.

Major Depressive Disorder (MDD) has been recognized as being under-diagnosed and under-treated for some time in People With HIV (PWH). The prevalence of MDD is two- to four-times more likely in PWH than in the general population. The compounded stigma of mental health issues with HIV infection itself further decreases the likelihood of access to optimal mental health treatment. The literature shows that 30 to 40% of patients with MDD, in general, fail to respond to the first line antidepressant treatment provided, despite adequate dosage, duration of treatment, and adherence. About 30% of adults with HIV are resistant to standard psychotherapeutic and psychopharmacological treatments for depression, thus suggesting the need for alternative treatment approaches.  Pramipexole a drug chosen for this study is believed to be superior to standard antidepressant therapy with regard to the treatment of MDD as well as (HIV-1-associated neurocognitive disorders) HAND among PWH. Escitalopram, a  Selective Serotonin Reuptake Inhibitor (SSRI) has been used as the active comparator treatment as it is a commonly used antidepressant therapy with PWH.

This study is a phase II, randomized, open-label, two-arm clinical trial evaluating the safety and efficacy of pramipexole extended release (ER) versus escitalopram for the treatment of major depressive disorder (MDD) and comorbid MDD with mild neurocognitive disorder (MND) in persons with HIV (PWH). Participants will be assessed comprehensively and briefly at intercurrent visits to monitor for toxicity, response to therapy, and to assess for dose changes. The study will take 24 weeks and will enroll people With HIV (PWH), 186 participants globally (93 per treatment arm), with a diagnosis of MDD alone or comorbid MDD and MND, aged 18-70 years on antiretroviral therapy for at least 3 moths and with HIV-1 RNA <200 copies/ml within 90 days of randomization. The Kenya Medical Research Institute/Walter Reed Project Clinical Research Center (KEMRI/WRP, CRC) Kericho will screen about 100 participants to enroll up to 50 into the study. Participants will be randomly assigned 1:1 to either arm 1 Pramipexole ER, gradually increased to 4.5 mg/day or Arm 2 (Escitalopram, gradually increased to 20mg/day) based on tolerance. Ethical approval will be obtained Kenya Medical Research Institute Scientific and Ethics Review Unit (KEMRI SERU), The Walter Reed Army Institute of Research (WRAIR) Human Subjects Protection Branch (HSPB) will also be involved in the approval process for this protocol. While WRAIR Institutional Review Board (IRB) is the IRB of record for US Army Medical Research Directorate-Africa (MRD-A), for this protocol WRAIR will rely on the KEMRI SERU for their ethical and regulatory review of the protocol. However, the WRAIR HSPB will conduct an administrative review of this protocol and SSA to ensure all DoD specific elements are included., Pharmacy and Poison Board (PPB) and National Council of Science and Technology Institute (NACOSTI).

The results of this study are expected to inform development of policy and guidelines for  management of MDD and/or comorbid MND..