Disposition Kinetics of Dolutegravir Among People Living With HIV With Major Depression in Nigeria
NCT ID: NCT07110831
Last Updated: 2025-08-08
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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NOT_YET_RECRUITING
PHASE4
168 participants
INTERVENTIONAL
2025-08-14
2028-03-31
Brief Summary
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The main questions it aims to answer are:
* Does fluoxetine (antidepressant) make participants taking anti-HIV (dolutegravir) feel better?
* What medical problems do participants have when taking fluoxetine and dolutegravir together?
* Does what people inherit from their parents affect the effectiveness and medical problems that participants have when taking fluoxetine and dolutegravir together? Researchers will compare depression treatments, fluoxetine and psychological treatment \[cognitive behavioural therapy (CBT)\] together to psychological treatment (CBT) alone among adults PLWH on anti-HIV drug (dolutegravir).
Participants on anti-HIV dolutegravir having depression will:
* Take both fluoxetine (daily) and CBT together or CBT alone for 3 months
* Visit the clinic once every week in the first month, then once every 2 weeks for checkups and tests including blood tests
* Keep a diary of their symptoms and other complaints
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Detailed Description
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Expert consensus is that selective serotonin-reuptake inhibitors (SSRIs) should be the first-line treatment for depression among PLWH. However, it is unclear whether SSRI therapy is effective in PLWH in low-middle-income countries (LMICs). There is an underrepresentation of LMICs in clinical studies involving PLWH and major depression despite the higher burden of PLWH and depression in LMICs than the high-income countries (HICs).
Fluoxetine is the preferred SSRI and most used for the treatment of depression in LMICs and is approved by their drug regulatory authorities. Fluoxetine is the most evaluated SSRI among PLWH with major depression but with different response rates among various ethnic groups reported. Furthermore, while fluoxetine was the most common SSRI used among the available clinical studies among PLWH, the studies did not report the clinical outcomes related to HIV care and cART.
Dolutegravir (DTG), an integrase strand transfer inhibitor, is the preferred and recommended first-line antiretroviral agent for adults and adolescents with HIV in LMICs. DTG is highly effective in suppressing HIV in both treatment-naive and experienced PLWHs, in addition to a low adverse effect profile and a high genetic barrier to developing drug resistance.
The cytochrome P450 (CYP) enzyme system metabolises fluoxetine, while the major enzyme that metabolises DTG is UGT1A1, with some contribution from CYP3A4/5. Fluoxetine and its major metabolite, norfluoxetine, may inhibit multiple enzymes involved in DTG metabolism, especially during chronic administration. A minor interaction via a membrane transporter mechanism may also be more pronounced with chronic use through the inhibition of the P-gp-mediated transport of DTG by fluoxetine. Patients on DTG report neuropsychiatric adverse events, and there is a relationship between plasma DTG trough concentration, neuropsychiatric adverse events, and UGT1A1 single nucleotide polymorphisms (SNPs). Thus, increases in DTG trough concentrations resulting from drug interaction are a potentially important concern.
Understanding potential drug interactions when fluoxetine and DGT-based cART are co-administered together will assist in optimising the dosing regimen, reducing adverse effects, and improving treatment outcomes among PLWH with major depression. To be able to recommend DTG and fluoxetine concomitant use, a prospective study involving PLWH with major depression is proposed. This study will address key knowledge gaps in drug interactions between fluoxetine and DTG among PLWH with major depression.
Conditions
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
SINGLE
Study Groups
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Fluoxetine Arm
Participants with a HAM-D score greater than 13 (moderate, moderately severe, and severe depression) will be recruited and allocated to the intervention group. The psychiatrist will commence the participants on fluoxetine (starting with 20mg daily). The psychiatrist will determine the dose of fluoxetine, and the dose may be adjusted during follow-up. Participants will receive Cognitive Behavioural Therapy (CBT) delivered by a Clinical psychologist in addition to fluoxetine as part of the standard routine care.
Fluoxetine
Participants in the intervention arm will receive oral fluoxetine capsules starting with 20mg daily for 12 weeks. The dose of the fluoxetine may be adjusted during follow-up by titrating the dose against the participants' response..
Cognitive-behavioral therapy
Participants with HAM-D score of between 8 and 13 (mild depression) will receive sessions of Cognitive Behavioural Therapy (CBT) as per standard routine care. Participants in the intervention arm will also receive sessions of CBT as per standard routine care.
Cognitive Behavioural Therapy (CBT) Arm
Participants with HAM-D score between 8 and 13 (mild depression) will be recruited and allocated to the control group. They will receive only Cognitive Behavioural Therapy (CBT) as per standard routine care.
Cognitive-behavioral therapy
Participants with HAM-D score of between 8 and 13 (mild depression) will receive sessions of Cognitive Behavioural Therapy (CBT) as per standard routine care. Participants in the intervention arm will also receive sessions of CBT as per standard routine care.
Interventions
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Fluoxetine
Participants in the intervention arm will receive oral fluoxetine capsules starting with 20mg daily for 12 weeks. The dose of the fluoxetine may be adjusted during follow-up by titrating the dose against the participants' response..
Cognitive-behavioral therapy
Participants with HAM-D score of between 8 and 13 (mild depression) will receive sessions of Cognitive Behavioural Therapy (CBT) as per standard routine care. Participants in the intervention arm will also receive sessions of CBT as per standard routine care.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Willing to provide informed consent.
* Confirmed HIV positive \[HIV-seropositive by Enzyme Linked Immunosorbent Assay (ELISA) and Western Blot assays\]
* Willingness to receive and or continue anti-HIV therapy (DTG-based cART) \& adhere to follow-up schedule
* Willing and able to comply with antidepressant medication(fluoxetine) regimen and scheduled follow-up visits
* Current depressive symptoms \[Subjects with depression (HAM-D-17 score ≥ 8)\]
* Adequate renal function (serum creatinine \< 1.5mg/dl)
* Adequate liver function \[aspartate aminotransferase (AST) and alanine transaminase (ALT) ≤1.5 x Upper Limits of Normal)
Exclusion Criteria
* Imminent risk of suicide- Acute suicidal ideation, gestures, or attempts
* Presence of psychotic symptoms or known diagnosis of a primary psychotic disorder
* Presence of symptoms of bipolar disorder
* Currently taking antipsychotic medication
* Pregnant or willing to get pregnant or lactation
* Current or chronic medical condition that would likely preclude adherence to protocol or completion of the trial (per investigator judgment)
* Antidepressants, mood stabilisers or other neuroleptics intake within three months
* Use of drugs other than cART, especially known enzyme inducers or inhibitors
* Abnormal ECG (e.g., prolonged QT interval)
* History of intolerance to study drug (fluoxetine)
18 Years
ALL
No
Sponsors
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Fogarty International Center of the National Institute of Health
NIH
State University of New York at Buffalo
OTHER
Roswell Park Cancer Institute
OTHER
College of Medicine University of Ibadan
UNKNOWN
University College Hospital, Ibadan, Nigeria
UNKNOWN
National Institute of Mental Health (NIMH)
NIH
University of Ibadan
OTHER
Responsible Party
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Waheed Adeola Adedeji
Lecturer
Principal Investigators
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Waheed A Adedeji
Role: PRINCIPAL_INVESTIGATOR
College of Medicine, University of Ibadan, Nigeria
Locations
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University College Hospital
Ibadan, Oyo State, Nigeria
Countries
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Central Contacts
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Facility Contacts
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References
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Adedeji WA, Ma Q, Raji AM, Cha R, Rasaki OM, Hutson A, Taiwo BO, Charurat ME, Yusuf OB, Fehintola FA, Gureje O, Morse GD. Prevalence of depression among people living with HIV in rural hospitals in South-Western Nigeria-Association with clinico-demographic factors. AIDS Res Ther. 2023 Dec 16;20(1):89. doi: 10.1186/s12981-023-00586-0.
Borghetti A, Calcagno A, Lombardi F, Cusato J, Belmonti S, D'Avolio A, Ciccarelli N, La Monica S, Colafigli M, Delle Donne V, De Marco R, Tamburrini E, Visconti E, Di Perri G, De Luca A, Bonora S, Di Giambenedetto S. SLC22A2 variants and dolutegravir levels correlate with psychiatric symptoms in persons with HIV. J Antimicrob Chemother. 2019 Apr 1;74(4):1035-1043. doi: 10.1093/jac/dky508.
Charlier C, Broly F, Lhermitte M, Pinto E, Ansseau M, Plomteux G. Polymorphisms in the CYP 2D6 gene: association with plasma concentrations of fluoxetine and paroxetine. Ther Drug Monit. 2003 Dec;25(6):738-42. doi: 10.1097/00007691-200312000-00014.
Reese MJ, Savina PM, Generaux GT, Tracey H, Humphreys JE, Kanaoka E, Webster LO, Harmon KA, Clarke JD, Polli JW. In vitro investigations into the roles of drug transporters and metabolizing enzymes in the disposition and drug interactions of dolutegravir, a HIV integrase inhibitor. Drug Metab Dispos. 2013 Feb;41(2):353-61. doi: 10.1124/dmd.112.048918. Epub 2012 Nov 6.
Wagner GJ, Maguen S, Rabkin JG. Ethnic differences in response to fluoxetine in a controlled trial with depressed HIV-positive patients. Psychiatr Serv. 1998 Feb;49(2):239-40. doi: 10.1176/ps.49.2.239.
Yagura H, Watanabe D, Kushida H, Tomishima K, Togami H, Hirano A, Takahashi M, Hirota K, Ikuma M, Kasai D, Nishida Y, Yoshino M, Yamazaki K, Uehira T, Shirasaka T. Impact of UGT1A1 gene polymorphisms on plasma dolutegravir trough concentrations and neuropsychiatric adverse events in Japanese individuals infected with HIV-1. BMC Infect Dis. 2017 Sep 16;17(1):622. doi: 10.1186/s12879-017-2717-x.
Fettiplace A, Stainsby C, Winston A, Givens N, Puccini S, Vannappagari V, Hsu R, Fusco J, Quercia R, Aboud M, Curtis L. Psychiatric Symptoms in Patients Receiving Dolutegravir. J Acquir Immune Defic Syndr. 2017 Apr 1;74(4):423-431. doi: 10.1097/QAI.0000000000001269.
Eshun-Wilson I, Siegfried N, Akena DH, Stein DJ, Obuku EA, Joska JA. Antidepressants for depression in adults with HIV infection. Cochrane Database Syst Rev. 2018 Jan 22;1(1):CD008525. doi: 10.1002/14651858.CD008525.pub3.
Lofgren SM, Nakasujja N, Boulware DR. Systematic Review of Interventions for Depression for People Living with HIV in Africa. AIDS Behav. 2018 Jan;22(1):1-8. doi: 10.1007/s10461-017-1906-3.
Kumar V, Encinosa W. Effects of HIV Medication Complexity and Depression on Adherence to HIV Medication. Patient. 2010 Mar 1;3(1):59-69. doi: 10.2165/11531090-000000000-00000.
Egbe CO, Dakum PS, Ekong E, Kohrt BA, Minto JG, Ticao CJ. Depression, suicidality, and alcohol use disorder among people living with HIV/AIDS in Nigeria. BMC Public Health. 2017 Jun 2;17(1):542. doi: 10.1186/s12889-017-4467-5.
Obadeji A, O Ogunlesi A, O Adebowale T. Prevalence and Predictors of Depression in People living with HIV/AIDS Attending an Outpatient Clinic in Nigeria. Iran J Psychiatry Behav Sci. 2014 Spring;8(1):26-31.
Nakimuli-Mpungu E, Bass JK, Alexandre P, Mills EJ, Musisi S, Ram M, Katabira E, Nachega JB. Depression, alcohol use and adherence to antiretroviral therapy in sub-Saharan Africa: a systematic review. AIDS Behav. 2012 Nov;16(8):2101-18. doi: 10.1007/s10461-011-0087-8.
Brown GR, Rundell JR, McManis SE, Kendall SN, Zachary R, Temoshok L. Prevalence of psychiatric disorders in early stages of HIV infection. Psychosom Med. 1992 Sep-Oct;54(5):588-601. doi: 10.1097/00006842-199209000-00006.
Arseniou S, Arvaniti A, Samakouri M. HIV infection and depression. Psychiatry Clin Neurosci. 2014 Feb;68(2):96-109. doi: 10.1111/pcn.12097. Epub 2013 Oct 30.
Satz P, Myers HF, Maj M, Fawzy F, Forney DL, Bing EG, Richardson MA, Janssen R. Depression, substance use, and sexual orientation as cofactors in HIV-1 infected men: cross-cultural comparisons. NIDA Res Monogr. 1997;172:130-55. No abstract available.
Other Identifiers
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UI/EC/22/0242
Identifier Type: -
Identifier Source: org_study_id
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