NCT01641367

A5288/MULTI-OCTAVE: Management Using Latest Technologies to Optimize Combination Therapy After Viral Failure

Management Using the Latest Technologies in Resource-limited Settings to Optimize Combination Therapy After Viral Failure (MULTI-OCTAVE)

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 545 (actual)
• Sponsor: Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections · Network
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The study was done to: * test a strategy of using a resistance test to choose anti-HIV drugs * see how well combinations of new anti-HIV drugs work to lower HIV infection * see if taking new anti-HIV drugs together is safe and tolerable * see if text messages improve people's anti-HIV drug-taking behavior (only at sites participating in the adherence study) * in people taking certain combinations of anti-HIV drugs with an anti-TB drug, compare how these drugs act in the body * to see how people do after they stop having frequent clinic visits as part of a research study

Detailed description

A5288 was an open-label phase IV, prospective interventional, strategy study in resource-limited settings (RLS) for HIV-1 infected participants with triple-class experience or resistance to nucleoside reverse transcriptase inhibitors (NRTIs), non-NRTIs (NNRTIs), and protease inhibitors (PIs) and who were failing their current regimen. The use of novel agents and contemporary clinical decision management tools that include standard genotyping and plasma HIV viral load (VL) monitoring were evaluated. The screening genotype results and antiretroviral (ARV) history were used to allocate potential participants to one of four Cohorts (A, B, C or D) and to select an associated ARV regimen based on the Cohort assignment. In brief, individuals assigned to Cohort A continued on the same PI as in their second-line regimen, with the ability to modify NRTIs. Those assigned to Cohort B who were negative for hepatitis B were randomized to receive RAL and DRV/RTV with either the best available NRTIs (Cohort B1) or ETR (Cohort B2). If they were positive for hepatitis B they were assigned to Cohort B3 and received RAL, DRV/RTV and either FTC/TDF or 3TC/TDF. Individuals assigned to Cohort C received RAL and DRV/RTV with the best available NRTIs. Those ineligible for Cohorts A, B or C were assigned to Cohort D and received the best available regimen that included study provided drugs and any locally provided drugs. At sites where feasible and relevant, the study evaluated an adherence support intervention. This involved a randomized comparison of a cell phone-based adherence support intervention plus local standard-of-care adherence support procedures (CPI+SOC) versus the SOC adherence support procedures. Participants enrolled to the study in Step 1. If a participant experienced a confirmed virologic failure (defined as two consecutive HIV-1 RNA measures \>= 1000 copies/mL) at/after 22 weeks on their Step 1 regimen, they had another genotype test performed and cohort/regimen selected for Step 2. With the exception of one additional visit 4 weeks after enrollment to Step 2, the visit schedule for Step 2 followed the participant's original Step 1 schedule throughout the remainder of follow up. Participants were followed in Steps 1 and 2 until 48 weeks after the last participant was enrolled to Step 1. During the first 48 weeks after Step 1 enrollment, clinic visits occurred at weeks 4, 12, 24, 36 and 48. After week 48, visits occurred every 12 weeks for adherence, safety and efficacy measures. Participants had a final step 1/2 visit between November 22, 2016 and February 13, 2017. At the final step 1/2 visit, participants taking RAL, ETR, or DRV who were unable to obtain these drugs locally (e.g., through local treatment programs), and were otherwise eligible, entered Step 3 and continued to receive these drugs through the study for up to 96 additional weeks. Step 3 participants were dispensed ARVs every 12 weeks and had clinical assessments every 24 weeks. The purpose of Step 3 was to assist participants with the transition back to local care. The primary analysis specified in the protocol and in the Statistical Analysis Plan was to estimate the proportion of participants in the overall study population who were virologically suppressed (HIV-1 RNA ≤200 copies/mL) at week 48 with a 95% confidence interval.

Conditions

• HIV-1 Infection

Interventions

Type	Name	Description
DRUG	Darunavir	Participants were administered darunavir orally as one 600 mg tablet twice a day (1200 mg per day) with food (taken with Ritonavir 100 mg twice a day \[200 mg per day\])
DRUG	Etravirine	Patients were administered Etravirine orally as two 100 mg tablets or one 200 mg tablet twice a day (400 mg per day) following a meal.
DRUG	Emtricitabine/tenofovir disoproxil fumarate	Patients were administered FTC/TDF orally as one fixed dose combination tablet (FTC 200 mg/TDF 300 mg) once daily, with or without food.
DRUG	Raltegravir	Participants were administered Raltegravir orally as one 400 mg tablet twice daily (800 mg per day), with or without food
DRUG	Second line ART regimens - based on a boosted protease inhibitor (bPI) plus two nucleoside analogues (NRTIs)	LPV/r and ATV/r were the preferred bPIs for second-line ART. TDF + (3TC or FTC) or AZT + 3TC were the most frequent NRTI backbones. Cohort A did not include any of the new drugs; therefore, it is distinct from Cohorts B, C, and D.
DRUG	Study provided drugs according to patient resistance profile (DRV, ETR, RTV, FTC/TDF) + any in country available drug as applicable & available	For Cohort D, in many situations a participant received the same regimen that patients are getting in Cohorts B and C if that was the best combination that can be obtained according to his/her resistance profile and drug availability (as for many countries there were no further drug options beyond the available study drugs).
OTHER	SOC adherence versus SOC+CPI adherence	* not participating in the adherence randomization; OR * randomized to SOC adherence; OR * randomized to SOC+CPI adherence.

Timeline

• Start date: 2013-02-22
• Primary completion: 2016-11-23
• Completion: 2018-12-31
• First posted: 2012-07-16
• Last updated: 2019-03-15
• Results posted: 2018-02-20

Locations

19 sites across 10 countries: Brazil, Haiti, India, Kenya, Malawi, Peru, South Africa, Thailand, Uganda, Zimbabwe