Clinical trial NCT01338025
Conditions: HIV Disease
Keywords: HIV Bridging Strategy
Sponsor: International Maternal Pediatric Adolescent AIDS Clinical Trials Group
Start date: 2011-03-01; Completion date: 2013-05-01
Enrollment: 33 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study was to compare the use of lamivudine (3TC) or emtricitabine (FTC) alone vs. continuing a failing highly active antiretroviral therapy (HAART) regimen in HIV infected children, adolescents and young adults. The study was to see if there were changes in the HIV virus and if there were differences in immune function, viral load and medication side effects between the two groups over 28 weeks. Participants were assigned to either take 3TC or FTC alone or continue on his/her current failing HAART regimen. During the first 28 weeks of this study, if the participant was randomized to the continue HAART arm, he/she was not switched to a different or new, potentially suppressive HAART regimen, but continued on the current failing HAART regimen. However, if continuing HAART, the participant might be switched to a new regimen if their provider felt that it was clinically needed or the participant met certain study endpoints (e.g., drop in CD4, increase in viral load).

At the end of 28 weeks, the participant had the choice of remaining on the assigned study group medication(s) or starting a new HAART regimen prescribed by his/her doctor. Then, they would be followed for another 24 weeks to compare the difference in immune function, viral load and medication side effects between the different groups.

Detailed description:
Currently, there is no clear consensus for managing virologic failure. Generally, failure of non-nucleoside reverse transcriptase inhibitor (NNRTI)-based therapy due to non-adherence is associated with high rates of NNRTI resistance, while failure of protease inhibitor (PI)-based therapy due to non-adherence carries a much lower risk of PI resistance. In the setting of incomplete adherence and virologic failure despite adherence education, an optimal strategy would be one that effectively bridges the period between the cessation of the failing regimen of highly active antiretroviral (ARV) therapy and initiation of a new HAART regimen. This would provide time for interventions to improve adherence to be effective while minimizing accumulation of additional drug resistance mutations. Given the compelling need for an effective bridging strategy, the limited evidence for the safety and efficacy of this bridging regimen, and the high level of acceptability of studying 3TC or FTC monotherapy as an effective alternative, P1094 proposed to conduct a randomized clinical trial (RCT) comparing use of 3TC or FTC monotherapy as a short-term bridging regimen vs. continuation of non-suppressive HAART in non-adherent subjects.

This study closed early due to lack of accrual, with only 33 of the target 344 participants enrolled. Therefore analyses, including the analysis of the primary outcome, are descriptive. Only analyses for Step 1 could be done (Step 2 was observational). The following secondary analyses could not be performed:

Changes in Genotypic HIV Drug Resistance From Baseline Changes HIV Replication Capacity \[Time Frame: 28 and 52 weeks\] Changes in CD4 Percent and CD4+ T Cell Count \[Time Frame: 52 weeks\] Changes in HIV-1 RNA Levels \[Time Frame: 52 Weeks\] Changes in Immune Activation \[Time Frame: 28 and 52 Weeks\] Number and Percent of Subjects With Adverse Clinical Outcomes \[Time Frame: 52 Weeks\] Adherence as Measured by 3-day Recall \[Time Frame: 52 Weeks\]

Arms: arm 1: In Step 1, subjects were randomized to continue their non-suppressive HAART regimen.

In Step 2, subjects either began a new HAART regimen, continued randomized treatment, or discontinued therapy while remaining on follow-up, as decided by their provider. arm 2: In step 1, subjects were randomized to receive 3TC or FTC (the choice of 3TC or FTC was left to the provider).

In Step 2, subjects either began a new HAART regimen, continued randomized treatment, or discontinued therapy while remaining on follow-up, as decided by their provider.
Interventions: intervention 1: HAART regimen intervention 2: 3TC or FTC monotherapy
Intervention descriptions: intervention 1: The study participant continued their non-suppressive HAART regimen as prescribed by their primary provider. intervention 2: The study participant was assigned to either 3TC or FTC monotherapy (the choice of 3TC or FTC was left to the provider.

Protocol documents: