DepressionPhase 4FLUDOPRESSNCT07110831

Disposition Kinetics of Dolutegravir Among People Living With HIV With Major Depression in Nigeria

A Phase 4 study testing Fluoxetine and Cognitive-behavioral therapy in people with Depression and HIV, run by University of Ibadan at 1 site in Nigeria.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts

Official record

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Trial summary

The goal of this clinical trial is to find out the usefulness and well-being of people when drugs for treating depression (fluoxetine) and HIV (dolutegravir) are used together. It will also learn about how safe it is to take fluoxetine and dolutegravir together by the people living with HIV (PLWH). Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Depression, HIV
What is being tested?: Fluoxetine and Cognitive-behavioral therapy
Type of treatment: Pill or oral medicine, Lifestyle or therapy programme
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 168 participants
Where: 1 siteNigeria
Study dates: 14 Aug 2025to 31 Mar 2028
Phase: Phase 4
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Males and females aged 18 years and above
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)

Who cannot join

Current substance use disorder
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

Show all 11Show fewer

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)

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Waheed A Adedeji contact

+2348038433259

wad_deji@yahoo.com

Fatai A Fehintola contact

fentolamine@yahoo.com

Nigeria1 site

University College Hospital
Ibadan, Oyo State, 200221
Waheed A Adedeji, +2348038433259, wad_deji@yahoo.com
Fatai A. Fehintola, +2348064251270, fentolamine@yahoo.com

Other trials in Nigeria

About this study

Official title: Influence of Fluoxetine on the Disposition Kinetics of Dolutegravir Among People Living With HIV With Major Depression in Nigeria

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

Read the detailed description

Depression is the most mental health disorder disorder among people living with HIV (PLWH) and is predictive of increased HIV-related morbidity and mortality. Treatment of depression in the setting of HIV is challenging as adding antidepressants in combination with combination antiretroviral therapy (cART) increases the pill burden and the potential for drug interactions. Studies have reported HIV medication complexity in patients comorbid with major depression to affect cART adherence. Optimal depression control among PLWH predicts and improves cART adherence and treatment outcomes.

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: Depression, HIV
Being tested: Fluoxetine, Cognitive-behavioral therapy
Keywords: Depression, Depressive Disorder, Major, HIV, Antidepressive Agents, Selective Serotonin Reuptake Inhibitors, Fluoxetine, Antiretroviral Therapy, Highly Active, Dolutegravir, Pharmacokinetics
Medical subject headings: Depression, Depressive Disorder, Major

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

FluoxetineDrug
Also called Prozac, Fluoxetine hydrochloride, Rapiflux, Sarafem
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 therapyBehavioural
Also called Psychotherapy, Cognitive Behavioral Therapy, Cognitive Behavioural Therapy, Cognitive Psychotherapy
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.

Study groups in NCT07110831
Study group	Role	What they receive
Fluoxetine Arm	Experimental	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. Receives: Drug: Fluoxetine; Behavioral: Cognitive-behavioral therapy
Cognitive Behavioural Therapy (CBT) Arm	Active comparator	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. Receives: Behavioral: Cognitive-behavioral therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

Mean change in the Hamilton Depression Rating Scale (HAM-D) scores from baseline to 12 weeks
The total HAM-D scores provide an indication of depression and, over time, a guide to evaluate response and recovery. The higher the HAM-D scores, the higher the severity of depression. HAM-D is graded as follows None 0-7 Mild 8-16 Moderate 17-23 Severe ≥ 24
Measured: Baseline to the end of treatment at 12 weeks
Mean changes in the AUC of dolutegravir
The effect of chronic administration of fluoxetine on the steady-state pharmacokinetics of dolutegravir and by intrasubject comparison in the participants. This will be assessed with mean changes in the Area under the plasma concentration-time curve (AUC) before and after the administration of fluoxetine.
Measured: Week 2 to the end of treatment at 12 weeks
Mean changes in the Cmax of doultegravir
The effect of chronic administration of dolutegravir on the steady-state pharmacokinetics of fluoxetine by intrasubject comparison in the participants. This will be assessed with mean changes in the Maximum plasma concentration (Cmax) before and after the administration of fluoxetine.
Measured: Week 2 to the end of treatment at 12 weeks
Mean changes in the Cmin of dolutegravir
Description: The effect of chronic administration of fluoxetine on the steady-state pharmacokinetics of dolutegravir and by intrasubject comparison in the participants. This will be assessed with mean changes in the Minimum plasma concentration(Cmin) before and after the administration of fluoxetine.
Measured: Week 2 to the end of treatment at 12 weeks
Mean changes in the AUC of fluoxetine
The effect of chronic administration of dolutegravir on the steady-state pharmacokinetics of fluoxetine by intrasubject comparison in the participants. This will be assessed with mean changes in the Area under the plasma concentration-time curve (AUC) before and after the administration of fluoxetine.
Measured: Week 2 to the end of treatment at 12 weeks
Mean changes in the Cmax of fluoxetine
The effect of chronic administration of dolutegravir on the steady-state pharmacokinetics of fluoxetine by intrasubject comparison in the participants. This will be assessed with mean changes in the Maximum plasma concentration (Cmax) before and after the administration of fluoxetine
Measured: Week 2 to the end of treatment at 12 weeks
Mean changes in the Cmin of fluoxetine
The effect of chronic administration of dolutegravir on the steady-state pharmacokinetics of fluoxetine by intrasubject comparison in the participants. This will be assessed with mean changes in the Minimum plasma concentration (Cmin) before and after the administration of fluoxetine.
Measured: Week 2 to the end of treatment at 12 weeks

Secondary outcomes (20)

Proportion of participants reporting grade 3 or 4 Adverse Events as Assessed by the DAIDS AE Grading Table Corrected Version 2.1
The Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events Corrected version 2.1 consists of parameters, or Adverse Events (AEs), with severity grading guidance that is used in DAIDS clinical trials for safety data reporting to maintain accuracy and consistency in the evaluation of AEs. The DAIDS AEs is graded as follows: Grade 1 mild event, Grade 2 moderate event, Grade 3 severe event, Grade 4 potentially life-threatening event and Grade 5 death
Measured: Baseline to weeks 2, 4, 8, and 12
Proportion of participants with depression remission at week 12
To determine the proportion of participants with depression remission at week 12 This will be measured as the proportion of subjects with HAM-D score of less than 8 (HAM-D<8)
Measured: Baseline to the end of treatment at 12 weeks
Proportion of participants with a change of greater than or equal to (≥) 50% in the depression score from baseline to weeks 6, 8, and 12
To determine the proportion of participants with a change of greater than or equal to (≥) 50% in the HAM-D scores from baseline to weeks 6, 8 and 12
Measured: Baseline to weeks 6, 8 and 12
Proportion of participants that drop out (study dropouts) during the study
To determine that proportion of participants that drop out (study dropouts) from baseline till the end of study at week 12.
Measured: Baseline to weeks 2, 4, 6, 8, and 12
Proportion of participants with viral suppression (≤ 50 copies/mL)
To determine the proportion of participants with HIV viral suppression ( viral load ≤ 50 copies/mL) at the end of study at week 12
Measured: Baseline to the end of study at week 12
Mean increase in the CD4 count of participants
To determine the mean changes in the CD4 counts of participants from baseline to the end of study at week 12
Measured: Baseline to the end of study at week 12
AUC of fluoxetine and norfluoxetine
To determine the Area under the plasma concentration-time curve (AUC) of fluoxetine and norfluoxetine using intensive and sparse pharmacokinetic sampling at steady state.
Measured: Weeks 2, 6,10 and 12
Cmax of fluoxetine and norfluoxetine
To determine the Maximum plasma concentration (Cmax) of fluoxetine and norfluoxetine using intensive and sparse pharmacokinetic sampling at steady state.
Measured: Weeks 2, 6,10 and 12
Cmin of fluoxetine and norfluoxetine
To determine the Area Minimum plasma concentration (Cmin) of fluoxetine and norfluoxetine using intensive and sparse pharmacokinetic sampling at steady state.
Measured: Weeks 2, 6,10 and 12
Tmax of fluoxetine and norfluoxetine
To determine the time to maximum observed plasma concentration (Tmax) of fluoxetine and norfluoxetine using intensive and sparse pharmacokinetic sampling at steady state.
Measured: Weeks 2, 6,10 and 12
Half-life (t1/2) of fluoxetine and norfluoxetine
To determine the elimination half-life (t1/2) of fluoxetine and norfluoxetine using intensive and sparse pharmacokinetic sampling at steady state.
Measured: Weeks 2, 6,10 and 12
Apparent Total Body Clearance (CL/F) of fluoxetine and norfluoxetine
To determine the Apparent Total Body Clearance (CL/F) of fluoxetine and norfluoxetine using intensive and sparse pharmacokinetic sampling at steady state.
Measured: Weeks 2, 6,10 and 12
Apparent Volume of Distribution (Vd/F) of of fluoxetine and norfluoxetine
To determine the Apparent Volume of Distribution (Vd/F) of fluoxetine and norfluoxetine using intensive and sparse pharmacokinetic sampling at steady state.
Measured: Weeks 2, 6,10 and 12
AUC of dolutegravir
To determine the Area under the plasma concentration-time curve (AUC) of dolutegravir using intensive and sparse pharmacokinetic sampling at steady state.
Measured: Weeks 2, 6,10 and 12
Cmax of dolutegravir
To determine the Maximum plasma concentration (Cmax) of dolutegravir using intensive and sparse pharmacokinetic sampling at steady state.
Measured: Weeks 2, 6,10 and 12
Cmin of dolutegravir
To determine the Minimum plasma concentration (Cmin) of dolutegravir using intensive and sparse pharmacokinetic sampling at steady state.
Measured: Weeks 2, 6,10 and 12
Tmax of dolutegravir
To determine the Time to maximum observed plasma concentration (Tmax) of dolutegravir using intensive and sparse pharmacokinetic sampling at steady state.
Measured: Weeks 2, 6,10 and 12
Half-Life (t1/2) of dolutegravir
To determine the elimination Half-Life (t1/2) of dolutegravir using intensive and sparse pharmacokinetic sampling at steady state.
Measured: Weeks 2, 6,10 and 12
Apparent Total Body Clearance (CL/F) of dolutegravir
To determine the Apparent Total Body Clearance (CL/F) of dolutegravir using intensive and sparse pharmacokinetic sampling at steady state.
Measured: Weeks 2, 6,10 and 12
Apparent Volume of Distribution (Vd/F) of dolutegravir
To determine the Apparent Volume of Distribution (Vd/F) of dolutegravir using intensive and sparse pharmacokinetic sampling at steady state.
Measured: Weeks 2, 6,10 and 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

14 Aug 202531 Mar 2028

First posted8 Aug 2025
Study start14 Aug 2025 (estimated)
Primary completion30 Sep 2027 (estimated)
Study completion31 Mar 2028 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (16)Papers the sponsor has linked to this study.
Other trials for DepressionStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: Single blind
Who is masked: Outcomes assessor
Enrolment: 168 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT07110831
Sponsor's protocol ID: UI/EC/22/0242
Other IDs: K43TW011995
Acronym: FLUDOPRESS
Status last verified: Jul 2025
First submitted: 15 May 2025
Last updated: 8 Aug 2025
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: De-identified participant data will be shared post-trial as per NIH and the University of Ibadan's policies.

Publications

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.
PubMed 38104102
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.
PubMed 30561642
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.
PubMed 14639062
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.
PubMed 23132334
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.
PubMed 9575014
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.
PubMed 28915895
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.
PubMed 27984559
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.
PubMed 29355886
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.
PubMed 28900756
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.
PubMed 22273276
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.
PubMed 28577548
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.
PubMed 24995027
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.
PubMed 22116638
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.
PubMed 1438661
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.
PubMed 24552630

Interested in taking part?

Waheed A Adedeji

+2348038433259

wad_deji@yahoo.com

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 8 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Influence of Fluoxetine on the Disposition Kinetics of Dolutegravir Among People Living With HIV With Major Depression in Nigeria
ClinicalTrials.gov ID: NCT07110831
Acronym / sponsor ID: FLUDOPRESS / UI/EC/22/0242
Conditions: Depression, HIV
Keywords: Depression, Depressive Disorder, Major, HIV, Antidepressive Agents, Selective Serotonin Reuptake Inhibitors, Fluoxetine, Antiretroviral Therapy, Highly Active, Dolutegravir
Phase: Phase 4
Study type: Interventional
Recruitment status: Not yet recruiting
Enrolment: 168 participants (estimated)
Lead sponsor: University of IbadanUniversity, hospital or other
Collaborators: Fogarty International Center of the National Institute of Health, State University of New York at Buffalo, Roswell Park Cancer Institute, College of Medicine University of Ibadan, University College Hospital, Ibadan, Nigeria, National Institute of Mental Health (NIMH)
Study start: 14 Aug 2025 (estimated)
Primary completion: 30 Sep 2027 (estimated)
Study completion: 31 Mar 2028 (estimated)
First posted: 8 Aug 2025 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Detailed description

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: Single blind (outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Fluoxetine Arm	Experimental	Drug: Fluoxetine, Behavioral: Cognitive-behavioral therapyParticipants 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.
Cognitive Behavioural Therapy (CBT) Arm	Active comparator	Behavioral: Cognitive-behavioral therapyParticipants 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

Males and females aged 18 years and above
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

Key exclusion criteria (11 listed)

Current substance use disorder
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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
FluoxetineAlso: Prozac, Fluoxetine hydrochloride, Rapiflux, SarafemParticipants 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..	Drug	Fluoxetine Arm
Cognitive-behavioral therapyAlso: Psychotherapy, Cognitive Behavioral Therapy, Cognitive Behavioural Therapy, Cognitive PsychotherapyParticipants 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.	Behavioural	Cognitive Behavioural Therapy (CBT) Arm, Fluoxetine Arm

Primary outcome

Mean change in the Hamilton Depression Rating Scale (HAM-D) scores from baseline to 12 weeks
Time frame: Baseline to the end of treatment at 12 weeks
The total HAM-D scores provide an indication of depression and, over time, a guide to evaluate response and recovery. The higher the HAM-D scores, the higher the severity of depression. HAM-D is graded as follows None 0-7 Mild 8-16 Moderate 17-23 Severe ≥ 24
Mean changes in the AUC of dolutegravir
Time frame: Week 2 to the end of treatment at 12 weeks
The effect of chronic administration of fluoxetine on the steady-state pharmacokinetics of dolutegravir and by intrasubject comparison in the participants. This will be assessed with mean changes in the Area under the plasma concentration-time curve (AUC) before and after the administration of fluoxetine.
Mean changes in the Cmax of doultegravir
Time frame: Week 2 to the end of treatment at 12 weeks
The effect of chronic administration of dolutegravir on the steady-state pharmacokinetics of fluoxetine by intrasubject comparison in the participants. This will be assessed with mean changes in the Maximum plasma concentration (Cmax) before and after the administration of fluoxetine.
Mean changes in the Cmin of dolutegravir
Time frame: Week 2 to the end of treatment at 12 weeks
Description: The effect of chronic administration of fluoxetine on the steady-state pharmacokinetics of dolutegravir and by intrasubject comparison in the participants. This will be assessed with mean changes in the Minimum plasma concentration(Cmin) before and after the administration of fluoxetine.
Mean changes in the AUC of fluoxetine
Time frame: Week 2 to the end of treatment at 12 weeks
The effect of chronic administration of dolutegravir on the steady-state pharmacokinetics of fluoxetine by intrasubject comparison in the participants. This will be assessed with mean changes in the Area under the plasma concentration-time curve (AUC) before and after the administration of fluoxetine.
Mean changes in the Cmax of fluoxetine
Time frame: Week 2 to the end of treatment at 12 weeks
The effect of chronic administration of dolutegravir on the steady-state pharmacokinetics of fluoxetine by intrasubject comparison in the participants. This will be assessed with mean changes in the Maximum plasma concentration (Cmax) before and after the administration of fluoxetine
Mean changes in the Cmin of fluoxetine
Time frame: Week 2 to the end of treatment at 12 weeks
The effect of chronic administration of dolutegravir on the steady-state pharmacokinetics of fluoxetine by intrasubject comparison in the participants. This will be assessed with mean changes in the Minimum plasma concentration (Cmin) before and after the administration of fluoxetine.

20 secondary outcomes

Proportion of participants reporting grade 3 or 4 Adverse Events as Assessed by the DAIDS AE Grading Table Corrected Version 2.1
Time frame: Baseline to weeks 2, 4, 8, and 12
Proportion of participants with depression remission at week 12
Time frame: Baseline to the end of treatment at 12 weeks
Proportion of participants with a change of greater than or equal to (≥) 50% in the depression score from baseline to weeks 6, 8, and 12
Time frame: Baseline to weeks 6, 8 and 12
Proportion of participants that drop out (study dropouts) during the study
Time frame: Baseline to weeks 2, 4, 6, 8, and 12
Proportion of participants with viral suppression (≤ 50 copies/mL)
Time frame: Baseline to the end of study at week 12
Mean increase in the CD4 count of participants
Time frame: Baseline to the end of study at week 12
AUC of fluoxetine and norfluoxetine
Time frame: Weeks 2, 6,10 and 12
Cmax of fluoxetine and norfluoxetine
Time frame: Weeks 2, 6,10 and 12
Cmin of fluoxetine and norfluoxetine
Time frame: Weeks 2, 6,10 and 12
Tmax of fluoxetine and norfluoxetine
Time frame: Weeks 2, 6,10 and 12
Half-life (t1/2) of fluoxetine and norfluoxetine
Time frame: Weeks 2, 6,10 and 12
Apparent Total Body Clearance (CL/F) of fluoxetine and norfluoxetine
Time frame: Weeks 2, 6,10 and 12
Apparent Volume of Distribution (Vd/F) of of fluoxetine and norfluoxetine
Time frame: Weeks 2, 6,10 and 12
AUC of dolutegravir
Time frame: Weeks 2, 6,10 and 12
Cmax of dolutegravir
Time frame: Weeks 2, 6,10 and 12
Cmin of dolutegravir
Time frame: Weeks 2, 6,10 and 12
Tmax of dolutegravir
Time frame: Weeks 2, 6,10 and 12
Half-Life (t1/2) of dolutegravir
Time frame: Weeks 2, 6,10 and 12
Apparent Total Body Clearance (CL/F) of dolutegravir
Time frame: Weeks 2, 6,10 and 12
Apparent Volume of Distribution (Vd/F) of dolutegravir
Time frame: Weeks 2, 6,10 and 12

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Aug 2025.
Results publication: PubMed 38104102Adedeji 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.
Results publication: PubMed 30561642Borghetti 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.
Results publication: PubMed 14639062Charlier 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.
Results publication: PubMed 23132334Reese 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.
Results publication: PubMed 9575014Wagner 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.
Results publication: PubMed 28915895Yagura 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.
Results publication: PubMed 27984559Fettiplace 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.
Results publication: PubMed 29355886Eshun-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.
Results publication: PubMed 28900756Lofgren 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.
Results publication: PubMed 22273276Kumar 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.
Results publication: PubMed 28577548Egbe 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.
Results publication: PubMed 24995027Obadeji 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.
Individual participant dataSharing planned: Yes. De-identified participant data will be shared post-trial as per NIH and the University of Ibadan's policies.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.

Waheed A Adedeji contact

+2348038433259

wad_deji@yahoo.com

Fatai A Fehintola contact

fentolamine@yahoo.com

Waheed A Adedeji principal investigator

College of Medicine, University of Ibadan, Nigeria

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Fluoxetine and Cognitive-behavioral therapy in people with Depression and HIV, run by University of Ibadan at 1 site in Nigeria.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 8 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Nigeria. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Waheed A Adedeji (+2348038433259, wad_deji@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean change in the Hamilton Depression Rating Scale (HAM-D) scores from baseline to 12 weeks (time frame: Baseline to the end of treatment at 12 weeks). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07110831, which also lists 16 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Aug 2025.