Lopinavir/Ritonavir as Single-Drug Therapy for Maintenance of HIV-1 Viral Suppression​

1.  Hypotheses, predictions, and scientific theories
2. Sample size and data in error analysis
3. Scientific methodology, including discovery science, model building and testing, hypothesis testing, and engineering

Clinical Trial

  • Hypothesis: Which pair of drugs will suppress HIV better? lopinavir/ritonavir monotherapy vs. continuing lopinavir/ritonavir and 2 nucleosides in HIV-infected patients with suppressed HIV replication.(JAIDS)
  • Predictions: Patients in whom monotherapy failed had significantly worse adherence (how correctly they follow medical advice) than patients who remained virally suppressed on monotherapy.(JAIDS)
  • Scientific Theories: Most of the patients maintained with lopinavir/ritonavir monotherapy remain with an undetectable viral load after 48 weeks. Failures of lopinavir/ritonavir monotherapy were not associated with the development of primary resistance mutations in the protease gene and could be successfully reinduced (introduced again) adding back prior nucleosides (a compound found in DNA and RNA).(JAIDS)
  • Sample Size/Error Analysis: Randomized, controlled, open-label (both the researchers and patients know what is going on), multicenter (multiple clinics), pilot clinical trial (small preliminary study). Forty-two patients were randomly assigned 1:1 to continue or stop the nucleosides. At baseline there were no significant differences between groups in median CD4 cells/μL (baseline). (JAIDS)
  • After 48 weeks of follow-up, percentage of patients remaining at <50 HIV RNA copies/mL (intention to treat, M = F) was 81% for the monotherapy group (95% Confidence Interval: 64% to 98%) vs. 95% for the triple-therapy group (95% CI: 86% to 100%); P = 0.34. Patients in whom monotherapy failed had significantly worse adherence than patients who remained virally suppressed on monotherapy. Monotherapy failures did not show primary resistance mutations in the protease gene and were successfully reinduced with prerandomization nucleosides. Mean change in CD4 cells/μL: +70 (monotherapy) and +8 (triple) (P = 0.27). Mean serum fasting lipids remained stable in both groups. No serious adverse events were observed.(JAIDS)
  • Conclusion: Most of the patients maintained with lopinavir/ritonavir monotherapy remain with undetectable viral load after 48 weeks. Failures of lopinavir/ritonavir monotherapy were not associated with the development of primary resistance mutations in the protease gene and could be successfully reinduced adding back prior nucleosides. (JAIDS)
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