An interventional study of switch in HIV/AIDS, sponsored by Niklaus Labhardt. Completed at 8 sites in Lesotho. Per ClinicalTrials.gov, last updated 2022-03-22.
Sponsored by Niklaus Labhardt · Not applicable, Interventional, and Treatment
This trial addresses the question of the viral load (VL) threshold for switching from first-line to second-line antiretroviral therapy (ART). The WHO currently sets the threshold at 1000 copies/mL. However, the optimal threshold for defining virological failure and the need to switch ART regimen has not been determined. In fact, people with VL levels of less than 1000 copies/mL, however, not fully suppressed, are at increased risk for drug resistance mutations (DRM) and subsequent virological failure. In resource-limited settings where VL monitoring is not as frequent as in high-income countries, this could have serious implications and patients may continue on a failing regimen for a long period. Our research consortium will conduct a multicenter, parallel-group, open-label, randomized clinical trial in a resource-limited setting to assess whether a threshold of 100 copies/mL compared to the WHO-defined threshold of 1000 copies/mL for switching to second-line ART among unsuppressed HIV-positive patients on first-line ART will lead to better outcomes.
Study background \& rational:
The Joint United Nations Programme on HIV/AIDS (UNAIDS) launched the 90-90-90 targets for 2020 based on the result of newly-acquired scientific evidence that - irrespective of CD4 count - early antiretroviral treatment (ART) for HIV-positive individuals is beneficial to them and prevents HIV transmission. UNAIDS expects that the 90-90-90 targets will lead to a reduction in the yearly global HIV incidence from 2 million currently to 500,000 by 2020.
A crucial step to achieve the third pillar of the UNAIDS 90-90-90 targets - 90% viral suppression among HIV-positive individuals on treatment - and thus ensure a successful treatment outcome is the monitoring and management of first-line ART failure.
Since 2013, the WHO recommends routine viral load (rVL) measurement as the preferred monitoring strategy in resource-limited settings and defines virological failure as confirmed VL 1000 copies/mL despite good adherence. Specifically, the guidelines recommend that in case of a VL ≥ 1000 copies/mL the patient should undergo enhanced adherence support and a second VL test 3 months later. A second VL ≥ 1000 copies/mL with confirmed good adherence would trigger the switch to a second-line regimen, whereas if the VL is \< 1000 copies/mL the patient should continue unaltered first-line ART. However, the optimal threshold for defining virological failure and the need for switching ART regimen has not yet been determined. In fact, people with VL levels of less than 1000 copies/mL, but not fully suppressed (usually defined as 50-100 copies/mL), are at a increased risk for drug resistance mutations (DRM) and subsequent virological failure. A recently published study from our research consortium in Lesotho indicates similar findings, demonstrating a significant accumulation of drug resistance mutations in patients with VL levels of less than 1000 copies/mL.
The VL threshold of 1000 copies/mL recommended by the WHO and the Lesotho national guidelines for the switch to second-line ART is likely to miss a substantial number of patients on first-line ART with persisting virus replication below 1000 copies/mL with DRM. In resource-limited settings where VL monitoring is not as frequent as in high-income countries, this could have serious implications: after a VL below 1000 copies/mL the patient may not receive a follow-up VL for up to a year, and thus may continue on a failing regimen for a long period of time. In conclusion, such patients are at increased risk for DRM, accumulation of further resistance mutations, drug-resistant virus transmission, and subsequent virological failure.
Study hypothesis:
Our research consortium hypothesizes that in patients on first-line ART with two consecutive unsuppressed VL measurements equal/more than 100 copies/mL, where the second VL is between 100 and 999 copies/mL, switch to second-line ART (intervention group) will lead to a higher rate of viral resuppression (VL \< 50 copies/mL) and is therefore superior compared to not switching to second-line ART according to WHO guidelines (control group, standard of care).
Study design:
Multicenter (2-12 centers), parallel-group (1:1 allocation), open-label, superiority, prospective randomized clinical study.
3,035 studies on the registry are indexed under Acquired Immunodeficiency Syndrome; 306 are open to participants now.
This study's enrollment of 80 is below the median of 96 across 2,251 interventional studies indexed under Acquired Immunodeficiency Syndrome.
Browse Acquired Immunodeficiency Syndrome studies →Niklaus Labhardt is the lead sponsor of 2 studies on the registry; none are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Line of therapy
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
switch to second-line ART
Other: switch
Standard of care: no switch to second-line ART
switch to second-line ART
viral suppression
Proportion of virologically suppressed (VL \< 50 copies/mL) participants 9 months after randomization.
Time frame: 9 months after randomization
Proportion of participants with different VL thresholds (VL <100, <200, <400, <1000 copies/mL) at 9 months after randomization
Time frame: 9 months after randomization
Adherence at 3, 6, 9 months, assessed by self-reported dose omission
Time frame: 3, 6, 9 months after randomization
Change in values (versus values at baseline) of body-weight (kg) at 9 months
Time frame: 9 months after randomization
Change in values (versus values at baseline) of haemoglobin (g/dL) at 9 months
Time frame: 9 months after randomization
Change in values (versus values at baseline) of CD4 count (cells/mL) at 9 months
Time frame: 9 months after randomization
Change in values (versus values at baseline) of lipids (total cholesterol, LDL, HDL, triglycerides; mmol/l) at 9 months
Time frame: 9 months after randomization
Change in values (versus values at baseline) of new clinical WHO 3 or 4 events (proportion) count at 9 months
Time frame: 9 months after randomization
Change in values (versus values at baseline) of deaths (all-causes) (proportion) at 9 months
Time frame: 9 months after randomization
Proportion of patients with adverse events and serious adverse events at 9 months after randomization
Time frame: 9 months after randomization
Long-term follow-up endpoint: Proportion of patients that are alive, retained in care and virologically suppressed (VL < 50 copies/mL) at 24 months
Time frame: 24 months after randomization
Proportion of virologically suppressed (VL < 50 copies/mL) participants by demographic groups (children vs pregnant women vs adults)
Time frame: 9 months after randomization
Proportion of virologically suppressed (VL < 50 copies/mL) participants by different VL groups at enrolment (VL 100-599 vs 600-999 copies/mL copies/mL)
Time frame: 9 months after randomization
Proportion of participants with viral resuppression (<50 copies/mL)
Time frame: 6 months after randomization
Sustained virologic failure
Proportion of participants with unsuppressed VL \>50 copies/mL at 6 and 9 months
Time frame: 6 and 9 months after randomization
Direct costs of each treatment arm
Time frame: 9 months and 24 months after randomization
Prevalence of major viral resistance mutations to first-line regimen in each treatment arm for all samples for which an RT-PCR amplification is successful
Time frame: 9 months after randomization
pre-specified subgroup: 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)
Time frame: 9 months after randomization
Plan to share: Undecided — IPD (baseline characteristics, outcomes, follow-up data) will eventually be shared after completion of the study upon request.
Ran from Aug 2017 to primary completion in May 2020, 33 months.
Of 641 non-industry interventional studies with no phase under Acquired Immunodeficiency Syndrome, half reached primary completion within 30 months of starting (the median), counting those still running; a quarter within 17 and three quarters within 45. This study's 33 months is close to that.
Counting every sponsor, half of 647 studies reached it within 29 months; a quarter within 17 and three quarters within 45.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Mar 2022. You cannot join it, but the record below documents what was studied.
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Acquired Immunodeficiency Syndrome →
Niklaus Labhardt