Managing first-line failure.

Area of Science:

• Infectious Diseases
• Virology
• Public Health

Background:

• The World Health Organization (WHO) recommends specific antiretroviral therapy (ART) regimens for patients failing first-line HIV treatment, typically involving boosted protease inhibitors and nucleos(t)ide reverse transcriptase inhibitors (NRTIs).
• Historically, these recommendations were based on expert opinion due to a lack of robust clinical trial data.

Purpose of the Study:

• To evaluate the efficacy and safety of the WHO standard of care for second-line HIV therapy.
• To compare the WHO standard of care with a novel regimen of boosted protease inhibitors and integrase inhibitors.
• To assess the effectiveness of a protease inhibitor monotherapy maintenance strategy following induction therapy.

Main Methods:

• Two large randomized clinical trials, SECOND LINE and EARNEST, were conducted.
• Patients failing first-line ART were randomized to different second-line treatment arms.
• Efficacy, toxicity, and development of drug resistance were monitored.

Main Results:

• Both the WHO standard of care and the novel boosted protease inhibitor/integrase inhibitor regimen demonstrated excellent response rates exceeding 80%.
• No significant differences in efficacy or toxicity were observed between these two regimens.
• A protease inhibitor monotherapy maintenance strategy was found to be inferior, leading to substantial protease inhibitor resistance (20%).

Conclusions:

• The WHO standard of care for second-line HIV therapy is validated by these trial results.
• A boosted protease inhibitor combined with an integrase inhibitor represents an effective alternative for second-line treatment.
• Protease inhibitor monotherapy is not suitable for public health strategies in resource-limited settings due to resistance concerns.