HIV infection Infections and Infestations
Conditions
Interventions
This is a non-randomised, single-arm study. Dovato 50 mg/300 mg will be given to all participants who are enrolled into the study. Participants will take daily oral Dovato from baseline for the 2-yea
Sponsors
Imperial College London
Eligibility
Sex/Gender
All
Age
18 Years to 100 Years
Inclusion criteria
Inclusion criteria: 1. HIV-1 positive 2. Age 18 years or over 3. Signed informed consent 4. Willing to switch therapy as per study protocol 5. Able to comply with the study protocol and tolerate the study regimen in the opinion of the investigator 6. On stable triple-drug antiretroviral therapy with no antiretroviral drug switches in the last 3 months and no prior use of dual antiretroviral therapy 7. Clinical diagnosis of legacy HABI with no evidence of active disease (as per protocol Section 4.2.2 Definition of legacy HABI) 8. Plasma HIV RNA <50 copies/mL at screening and on at least one other occasion over the last 12 months 9. Undetectable cerebrospinal fluid HIV RNA (<200 copies/mL) at screening 10. For patients assigned female at birth one of the following conditions must apply: 10.1. Non-childbearing potential defined as either post-menopausal (12 months of amenorrhea without an alternate medical cause), or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy OR 10.2. Child-bearing potential with a negative pregnancy test at Baseline and agrees to use one of the following methods of contraception to avoid pregnancy: 10.2.1. Complete abstinence from penile-vaginal intercourse from at least 2 weeks prior to administration of study drug, throughout the study, and for at least 2 weeks after discontinuation of all study medications 10.2.2. Partner sterilisation, confirmed prior to the participant's entry into the study, provided that the sterilised partner is the sole partner for that participant 10.2.3. A contraceptive method that is highly effective (with an expected failure rate of <1% per year) (see protocol Section 6.3.1 Study sanctioned highly effective contraceptive methods, for a list of acceptable highly effective methods of contraception).
Exclusion criteria
Exclusion criteria: 1. History of CSF HIV RNA escape (defined as a paired CSF HIV RNA greater than plasma HIV RNA) 2. History of plasma or cerebrospinal fluid HIV-drug resistance 3. Contraindication to dual antiretroviral therapy 4. Contraindication to lumbar puncture examination 5. Contraindication to MRI scan (claustrophobia, metal implants or other reasons) 6. ALT =5 times the upper limit of normal, OR ALT =3 times the upper limit of normal and bilirubin =1.5 times the upper limit of normal (with >35% direct bilirubin) 7. Creatinine clearance of <30 mL/min 8. Clinically significant abnormalities in screening laboratory results 9. Evidence of hepatitis B co-infection or, if at risk of hepatitis B, not hepatitis B immune 10. Chronic hepatitis C infection anticipated to require the introduction of new hepatitis C virus therapy (e.g. with oral direct-acting antivirals) prior to the primary endpoint of the study. 11. Current alcohol abuse or drug of abuse dependence 12. Severe mental health conditions that make patient unlikely to adhere to protocol 13. Active opportunistic infection or significant co-morbidities with a life expectancy of less than 2 years 14. Current disallowed concomitant medication as per SmPC 15. History or presence of allergy to the study drugs or their components 16. Pregnancy or breast/chestfeeding or patient envisages becoming pregnant during the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of individuals with undetectable HIV RNA in the cerebrospinal fluid after study intervention The primary endpoint is a composite endpoint based on: 1. Cerebrospinal fluid HIV RNA assessed at month 12 2. Cerebrospinal fluid HIV RNA assessed clinically at any time from baseline due to new onset of neurological symptoms which may be in keeping with cerebrospinal fluid escape Measured either at 12 months or at an earlier timepoint if individuals have neurological symptomatology | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Clinical parameters measured at baseline, 12 and 24 months, including: 1.1. Cognitive function measured using Montreal Cognitive Assessment (MoCA), Trail Making Test 1.2. Quality of life and wellbeing of people with HIV measured using HIV Positive Outcomes questionnaire 1.3. Depression measured using Patient Health Questionnaire (PHQ-9) 1.4. Anxiety measured using Generalized Anxiety Disorder 2 (GAD-2) 2. Plasma HIV RNA measured using local hospital laboratory HIV RNA assay at all study visits over 12 and 24 months 3. Cerebrospinal fluid parameters measured using local hospital laboratory protein, glucose, albumin, microscopy, HIV RNA CSF assays at baseline and 12 months 4. Cerebral MRI parameters measured at baseline and 12 months | — |
Countries
England, United Kingdom
Contacts
Public ContactNicki Doyle
Outcome results
None listed