Phase 4
N=191
Integrase and Maraviroc Intensification in Neurocognitive Dysfunction (InMIND)
HIV Infections
Bottom Line
View on ClinicalTrials.gov: NCT02519777 ↗Enrolled (actual)
191
Serious AEs
14.2%
Results posted
Mar 2022
Primary outcome: Primary: Change in Normalized Composite Neurocognitive Test Score at Week 48 From Baseline — 0.20; 0.26; 0.31 total neurocognitive z-score — p=0.60
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 4
- Interventions
- Placebo for maraviroc (MVC) (Drug); Placebo for dolutegravir (DTG) (Drug); Dolutegravir (DTG) (Drug); Maraviroc (MVC) (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Primary completion
- Dec 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change in Normalized Composite Neurocognitive Test Score at Week 48 From Baseline |
0.20; 0.26; 0.31 | 0.60 |
| SECONDARY Number of Participants With Treatment Related Adverse Events (AEs) |
3; 5; 7 | — |
| SECONDARY Change in Normalized Composite Neurocognitive Test Score at Weeks 24, 72, and 96 From Baseline |
0.14; 0.18; 0.20; 0.29; 0.32; 0.37 | 0.61 |
| SECONDARY Change in Functional Status Scores |
0.29; 0.43; 0.15; 0.38; 0.45; 0.10 | 0.99 |
| SECONDARY Number of Participants With Plasma HIV-1 RNA Greater Than or Equal to 50 Copies/mL |
3; 1; 1; 3; 0; 1 | — |
| SECONDARY CD4+ T-cell Counts |
660; 669; 773; 638; 691; 758 | — |
| SECONDARY Change in CD4+ T-cell Count |
-13; -33; 42; -43; -19; 21 | 0.67 |
| SECONDARY CD8+ T-cell Counts |
757; 752; 862; 742; 731; 856 | — |
| SECONDARY Change in CD8+ T-cell Count |
-29; -61; 44; -45; -82; 35 | 0.63 |
| SECONDARY Change in Log10 sCD14 in Plasma at Week 48 From Baseline |
0.04; 0.03; 0.01 | 1.00 |
| SECONDARY Change in Log10 MIP-1 Beta in Plasma at Week 48 From Baseline |
0.05; -0.02; 0.30 | 0.52 |
| SECONDARY Change in Log10 sTNFr-II in Plasma at Week 48 From Baseline |
0.02; 0.01; 0.00 | 0.91 |
| SECONDARY Change in Log10 VCAM in Plasma at Week 48 From Baseline |
0.01; 0.00; 0.00 | 0.70 |
| SECONDARY Change in Log10 MIP-1 Beta in Cerebrospinal Fluid (CSF) at Week 48 From Baseline |
-0.24; -0.32; 0.17 | 0.99 |
| SECONDARY Change in Log10 IP-10 in CSF at Week 48 From Baseline |
0.02; -0.11; -0.36 | 0.59 |
| SECONDARY Change in Log10 Neopterin in CSF at Week 48 From Baseline |
0.01; -0.06; -0.17 | 0.90 |
| SECONDARY Change in Log10 NFL in CSF at Week 48 From Baseline |
-0.02; -0.05; 0.00 | 0.52 |
Summary
People infected with HIV often have cognitive dysfunction even if they are on antiretroviral therapy (ART) and have undetectable viral loads. The study evaluated if the addition of maraviroc (MVC) and dolutegravir (DTG) (which are two antiretroviral [ARV] medications) to participants' existing ART regimens improved participants' neurocognitive performance.
Eligibility Criteria
Inclusion Criteria
- HIV-1 infection, documented by:
- a licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen or plasma HIV-1 RNA viral load. NOTE: The term "licensed" refers to a United States Food and Drug Administration (FDA)-approved kit, which is required for all IND studies, or for sites located in countries other than the United States, a kit that has been certified or licensed by an oversight body within that country and validated internally. Non-US sites are encouraged to use US FDA-approved methods for IND studies. WHO (World Health Organization) and CDC (Centers for Disease Control and Prevention) guidelines mandate that confirmation of the initial test result must use a test that is different from the one used for the initial assessment. A reactive initial rapid test should be confirmed by either another type of rapid assay or an E/CIA that is based on a different antigen preparation and/or different test principle (eg, indirect versus competitive), or a Western blot or a plasma HIV-1 RNA. OR
- Documentation of HIV diagnosis in the medical record by a healthcare provider.
- On current ART for at least 6 months prior to study entry with no interruption in treatment of greater than or equal to 7 consecutive days. Note: The following ART changes are allowed:
- Tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide fumarate (TAF)/TAF-containing fixed-dose combination regimens
- Ritonavir (RTV) to cobicistat (COBI)/COBI-containing fixed-dose combination regimens
- No plans to change ART while on study. Note: The following planned ART changes are allowed:
- TDF to TAF/TAF-containing fixed-dose combination regimens
- RTV to COBI/COBI-containing fixed-dose combination regimens
- HIV-1 plasma RNA less than 50 copies/mL obtained within 90 days prior to study entry by any FDA-approved assay at any United States laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent, or at any network-approved non-US laboratory that operates in accordance with Good Clinical Laboratory Practices (GCLP) and participates in appropriate external quality assurance programs.
- No more than one HIV-1 plasma RNA greater than or equal to 50 and less than 200 copies/mL (only one "blip") in the past 6 months with a subsequent HIV-1 plasma RNA less than 50 copies/mL. NOTE: There should be no plasma HIV-1 RNA greater than 200 copies/mL within the 6 months prior to study entry.
- HAND diagnosis (ANI, MND, or HAD) within 60 days prior to study entry. HAND is defined as at least mild impairment on neurocognitive testing (more than one standard deviation below appropriate normative data in two domains of functioning) and no severely confounding factors.
- Screening laboratory values obtained within 60 days prior to study entry by any US laboratory that has a CLIA certification or its equivalent, or at any network-approved non-US laboratory that operates in accordance with GCLP and participates in appropriate external quality assurance programs:
- Absolute neutrophil count (ANC) greater than or equal to 500/mm^3
- Hemoglobin greater than or equal to 7.5 g/dL
- Platelet count greater than or equal to 40,000/mm^3
- Creatinine less than or equal to 2.0 x upper limit of normal (ULN)
- Aspartate transaminase (AST) less than or equal to 5 x ULN
- Alanine transaminase (ALT) less than 3 x ULN
- Alkaline phosphatase less than or equal to 5 x ULN
- Total bilirubin less than 1.5 x ULN. NOTE: If the potential participant is taking an indinavir (IDV)- or atazanavir (ATV)-containing regimen at the time of screening, total bilirubin less than or equal to 5 x ULN is acceptable.
- Creatinine clearance (CrCl) greater than or equal to 60 mL/min, either measured or estimated by Cockcroft-Gault equation. NOTE: A
Data sourced from ClinicalTrials.gov (NCT02519777). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.