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Dolutegravir-based maintenance monotherapy versus dual therapy with lamivudine: a planned 24 week analysis of the DOLAM randomized clinical trial
- Source :
- The Journal of antimicrobial chemotherapy. 73(7)
- Publication Year :
- 2018
-
Abstract
- No controlled comparisons between dolutegravir/lamivudine or dolutegravir maintenance therapy have been done. We hypothesized that these options would have similar efficacy to triple ART.We used an open-label non-inferiority randomized controlled trial comprising two phases: phase A was established to test that experimental arms did not have an unacceptable (≥5%) failure rate; phase B was intended to include the full number of patients followed for 48 weeks. Treated HIV-1-infected adults with viral load50 copies/mL for ≥12 months, no prior viral failure or resistance mutations to study drugs, nadir CD4200 cells/mm3, and hepatitis B virus surface antigen negative were randomized 1:1:1 to maintain triple therapy (control arm), or to switch to dolutegravir/lamivudine, or to dolutegravir monotherapy stratifying by anchor drug. Premature discontinuation was considered if viral failure or therapy interruption due to adverse events, concurrent illness, protocol deviation or patient's wish occurred. Blips were registered. Planned phase A results at 24 weeks are reported here. The study is registered at EudraCT: 201500027435.Ninety-one (control, n = 31; dual therapy, n = 29; monotherapy, n = 31) patients were randomized. Three patients (none previously exposed to integrase inhibitors) prematurely discontinued treatment due to viral failure: dolutegravir/lamivudine (n = 1), no resistance mutations (subject A); dolutegravir (n = 2), N155H, S147G and Q148R resistance mutations (subject B), and E138K, G140S and N155H resistance mutations (subject C). There were no discontinuations for other reasons. One patient (dolutegravir/lamivudine) experienced a blip in viral load. The Data Safety Monitoring Board recommended stopping the dolutegravir monotherapy arm.In contrast to dolutegravir/lamivudine, a higher than expected risk of viral failure with development of cross-resistance integrase mutations occurred with dolutegravir maintenance monotherapy.
- Subjects :
- 0301 basic medicine
Microbiology (medical)
Adult
Male
medicine.medical_specialty
Anti-HIV Agents
Pyridones
030106 microbiology
Integrase inhibitor
HIV Infections
Piperazines
law.invention
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Pharmacotherapy
Randomized controlled trial
Maintenance therapy
law
Internal medicine
Antiretroviral Therapy, Highly Active
HIV Seropositivity
Oxazines
medicine
Humans
Pharmacology (medical)
030212 general & internal medicine
HIV Integrase Inhibitors
Pharmacology
business.industry
Lamivudine
Middle Aged
Viral Load
Discontinuation
Infectious Diseases
chemistry
Dolutegravir
Mutation
HIV-1
RNA, Viral
Drug Therapy, Combination
Female
business
Viral load
Heterocyclic Compounds, 3-Ring
medicine.drug
Subjects
Details
- ISSN :
- 14602091
- Volume :
- 73
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- The Journal of antimicrobial chemotherapy
- Accession number :
- edsair.doi.dedup.....7950295b024322188a326f3c2759d0be