Virologic Outcomes of Lamivudine/Dolutegravir in Virologically suppressed subjects with Expected or confirmed Resistance to Lamivudine (VOLVER study).
- Conditions
- HIVTherapeutic area: Diseases [C] - Virus Diseases [C02]
- Registration Number
- EUCTR2021-000290-84-ES
- Lead Sponsor
- Seimc-Gesida Foundation
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 117
a. Adults (? 18 years old) with HIV-1 infection able to understand and give informed written consent.
b. Stable ART in the 12 weeks prior to screening visit.
- Only switch for tolerability/convenience/access reasons to generic drugs or switch from ritonavir to cobicistat or TDF to TAF would be allowed in the 12-week window and as long as the components of the regimen are unchanged.
c. Viral load <50 copies/mL at screening and in the year prior to study entry.
- A blip (50-500 copies/ml) would be allowed within 48 weeks prior to inclusion in the study, if preceded and followed by an undetectable VL determination.
d. CD4 count > 200 cel/µL at screening.
e. History of 3TC resistance: either confirmed historical 3TC resistance (historical RNA Sanger or RNA NGS>20% threshold genotype with M184V/I mutation) OR suspected historical 3TC resistance.
- Suspicion of past 3TC resistance is defined as any of the following:
i. Previous treatment with only 2 NRTIs (1 of them being emtricitabine or 3TC [XTC]).
ii. Two consecutive VL > 200 cp/mL while on treatment including XTC.
iii. One VL > 200 cp/mL while on treatment including XTC PLUS change of ART as consequence of that elevated VL.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 117
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 117
a. Participants with M184V/I or K65R in screening visit proviral DNA Sanger
genotype.
b. Prior virologic failure (VF) under integrase inhibitor (INSTI)- based regimen.
defined as two consecutive VL > 200 copies/mL while receiving INSTI
regardless of genotypic test results
c. INSTI resistance mutations in historical RNA genotype.
d. Positive Surface Hepatitis B Ag (HBAgS) OR negative HBAgS and negative
hepatitis B surface antibody (anti-HBs) with positive anti-core antibody (anti-
HBc) and positive HBV DNA.
e. Pregnant, breastfeeding women, women with a positive pregnancy test at the
time of screening, sexually active fertile women wishing to conceive or unwilling
to commit to contraceptive methods (see Appendix 1 for the accepted list of the
highly effective methods for avoiding pregnancy), for the duration of the study
and until 4 weeks after the last dose of study medication. All women are
considered fertile unless they have undergone a sterilizing surgery or are over
the age of 50 with spontaneous amenorrhea for over 12 months prior to study
entry.
f. Patients with active opportunistic infections or cancer requiring intravenous
treatment and/or chemotherapy at screening.
g. Any comorbidities or treatment with experimental drugs that according to the
investigator could bias study results or entail additional risks for the participant.
h. Participants receiving other medications that according to study drug label are
contraindicated.
i. Severe hepatic impairment (Class C) as determined by Child-Pugh
classification.
j. Alanine aminotransferase (ALT) over 5 times the upper limit of normal (ULN) or
ALT over 3xULN and bilirubin over 1.5xULN.
k. Unstable liver disease (as defined by the presence of ascites, encephalopathy,
coagulopathy, hypoalbuminemia, oesophageal or gastric varices, or persistent
jaundice), cirrhosis, known biliary abnormalities (apart from hyperbilirubinemia
or jaundice due to Gilbert's syndrome or asymptomatic gallstones);
l. Creatinine clearance of <30 mL/min/1.73m2 via CKD-EPI method.
m. Any verified Grade 4 laboratory abnormality that to the investigators criteria
would affect the safety of the participant if included in the study.
n. History or presence of allergy to dolutegravir or lamivudine.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method