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A5288: MULTIOCTAVE, Management Using the Latest Technologies in Resource-limited Settings to Optimize Combination Therapy After Viral Failure
This is a mult-country clinical trial being conducted in Brazil, Haiti, India, Kenya, Malawi, Peru, South Africa, Thailand, Uganda, and Zambia under the AIDS Clinical Trials Group (ACTG) and funded by the U.S. National Institutes of Health.
A5288 is a multi-step, open-label phase IV, prospective, interventional strategy study in resource-limited settings (RLS) for HIV-infected participants with triple-class experience or resistance (ie, to nucleoside reverse transcriptase inhibitors [NRTIs], non-NRTIs [NNRTIs], and protease inhibitors [PIs]) who are failing their current second-line ART regimen. The use of novel agents and contemporary management tools that include standard genotyping and plasma viral load (VL) monitoring will be evaluated. The screening genotype results and antiretroviral (ARV) history will be used to allocate study candidates to one of four treatment cohorts
Primary Objective: To use novel agents and contemporary management tools, including standard genotyping to select an appropriate third-line regimen, interventions to improve adherence and plasma viral load (VL) monitoring, in order to achieve a ≥65% rate of virologic control at 48 weeks of follow-up.
- To characterize changes in HIV-1 RNA and CD4+ T-cell counts over 48 weeks and durability of responses after 48 weeks, as well as clinical outcomes (AIDS-defining and non-AIDS-defining events, hospitalizations, and deaths) in four treatment groups (Cohorts A-D).
- To characterize the tolerability of the regimens in four treatment groups (Cohorts A-D).
- To characterize changes in metabolic outcomes, including fasting lipids at 48 weeks among the regimens in four treatment groups (Cohorts A-D).
- To assess the effect of a cell phone-based adherence intervention + standard of care (CPI+SOC) compared with SOC adherence procedures on the rate of virologic control at 48 weeks of follow-up.
- To determine the safety of combinations of third-line ARV therapy in terms of rates of treatment modification or discontinuation for the treatment of HIV-1 infection and to characterize drug-associated toxicities.
- To compare changes in HIV-1 RNA and CD4+ T-cell counts over 48 weeks, durability of responses after 48 weeks, and clinical outcomes (AIDS-defining and non-AIDS-defining events and deaths) of CPI+SOC versus SOC adherence procedures.
- To compare the tolerability of third-line regimens among participants receiving CPI+SOC versus SOC adherence procedures.
- In Cohort B, among participants without active hepatitis B infection, to explore whether the combination of ETR+DRV/RTV+RAL (etravirine, ritonavir-boosted darunavir, raltegravir) is associated with better virologic control, CD4+ T-cell responses, and tolerability than best available NRTIs+DRV/RTV+RAL.
- To determine the prevalence at enrollment of resistance mutations detected on a population-based and minority-variant level in the four treatment groups (Cohorts A-D), and to explore prevalence by viral subtype.
- To describe the mutation patterns and accumulation of mutations over time in the participants experiencing viral failure.
- To evaluate the impact of predictors, including viral subtype, baseline mutations and polymorphisms occurring in env, gag, protease, reverse transcriptase, and integrase (IN) - detected by population-based genotyping and minority-variant analysis - on the virologic outcomes in the four treatment groups (Cohorts A-D).
- To evaluate the association of adherence to the study regimens with virologic outcome.
- To provide resource utilization and quality of life (QOL) data to support modeling of cost-effectiveness of ART selected using treatment history and standard genotyping, as well as cost-effectiveness of the adherence intervention.
- To estimate the incidence of immune reconstitution inflammatory syndrome (IRIS) and describe the clinical presentation and associated pathogens and/or inflammatory conditions.
Step 3 Objective: To evaluate longer-term toxicity, and virologic, immunologic, and clinical outcomes of regimens containing RAL, DRV/RTV, or ETR after completion of Step 1 and/or 2.