Background
Methods
Setting and design
Screening, randomization and interventions
Inclusion Criteria | Exclusion Criteria |
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a) On non-nucleoside reverse transcriptase inhibitor (NNRTI) based ART (standard first-line regimen in Lesotho) for at least 6 months b) Two consecutive VL ≥100 copies/mL, with the latest VL between 100 and 999 copies/mL c) Participant lives and/or works in the district of Butha-Buthe and declares to seek follow-up at one of the study-facilities d) Signed written informed consent. For children aged < 18 years and illiterate patients, a literate caregiver or witness, respectively, must provide written informed consent (see Ethical considerations). | a) On ART less than 6 months b) On protease inhibitor (PI) or integrase inhibitor containing ART regimen c) Poor adherence (self-reported at least 1 dose of a once-daily regimen missed in the last 4 weeks, respectively two doses of a twice-daily-regimen) d) Clinical WHO stage 3 or 4 at enrolment |
Primary endpoint
Secondary, exploratory, and subgroup endpoints
Definition | Time point following randomization | Remarks | |
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Secondary endpoints | |||
VL level | Proportion of participants with different levels (VL < 100, < 200, < 400, < 1000 copies/mL) | 9 months | |
VL at 6 months | Proportion of participants with viral resuppression (< 50 copies/mL) | 6 months | |
Sustained virologic failure | Proportion of participants with unsuppressed VL > 50 copies/mL at 6 and 9 months | 6 and 9 months | |
Adherence | Proportion of participants with good adherence | 3, 6, and 9 months | Definition of “good adherence”: self-reported no dose missed of a once-daily-regimen, respectively less than two doses of a twice-daily-regimen, during the last month |
Clinical outcomes | Change in values (versus values at baseline) of body-weight (kg), CD4-cell count (cells/μL), haemoglobin (g/dL), lipids (total cholesterol, LDL, HDL, triglycerides; mmol/L); proportion of patients with newly-recorded clinical WHO-stage 3 or 4 events; proportion of patients died (all-causes) | 9 months | |
(Serious) Adverse Events | Proportion of patients with Adverse Events (AE) or Serious Adverse Events (SAE) | 9 months | AE and SAE are graded according to Common Terminology Criteria for Adverse Events (v4.0, published May 28, 2009) |
Long-term follow-up | Proportion of patients that are alive, retained in care and virologically suppressed | 24 months | Definition of “virologically suppressed”: < 50 copies/mL |
Potential effect modifiers | |||
Primary endpoint by demographic groups | Viral resuppression by adults vs children vs pregnant women | 9 months | Definition of “viral resuppression”: < 50 copies/mL |
Primary endpoint by baseline VL groups | Viral resuppression by baseline VL 100–599 vs 600–999 copies/mL | 9 months | Definition of “viral resuppression”: < 50 copies/mL |
Exploratory endpoints | |||
Cost-effectiveness | Staff costs (clinical and laboratory); costs of ARVs; costs of drugs for prevention of opportunistic infections and other concomitant medications; laboratory costs (CD4 cell count, VL, blood chemistry, blood count and other diagnostic procedures); estimation of health impact/benefits outcomes (e.g. DALY) | Between baseline and 9 months and 24 months (long-term follow-up) | |
Drug resistance mutations | Prevalence of major drug resistance mutations a) on all baseline VLs and b) on all VLs that remain unsuppressed (> 50 copies/mL) at 9 months for all samples for which an RT-PCR amplification is successful | At baseline and at 9 months | Definition of “major drug resistance mutations”: Stanford University HIV Resistance Database (http://hivdb.stanford.edu) |
Subgroup endpoint | |||
Log-drop | Viral resuppression among individuals with a > 0.5 drop in log10 VL between the first screening VL and the second screening VL (i.e. VL at enrolment) | 9 months | Definition of “viral resuppression”: < 50 copies/mL |