Immune Reconstitution in Severely Immunosuppressed Antiretroviral-Naive HIV-1-Infected Patients Starting Efavirenz, Lopinavir-Ritonavir, or Atazanavir-Ritonavir Plus Tenofovir/Emtricitabine: Final 48-Week Results (The Advanz-3 Trial).

Abstract

BACKGROUND:

Few randomized clinical trials have investigated antiretroviral regimens in very advanced HIV-1-infected patients. The objective was to study the immune reconstitution in very immunosuppressed antiretroviral-naive, HIV-1-infected individuals by comparing an efavirenz-based regimen with 2 ritonavir-boosted protease inhibitor regimens.

METHODS:

Randomized, controlled, open-label, multicenter clinical trial. Eighty-nine HIV-1-infected antiretroviral-naive patients with <100 CD4 cells per cubic millimeter were randomly assigned in a 1:1:1 ratio to efavirenz (n = 29), atazanavir/ritonavir (n = 30), or lopinavir/ritonavir (n = 30) combined with tenofovir plus emtricitabine. The primary outcome was median increase in CD4 cell count at week 48. Secondary end points were the proportion of patients with HIV-1 RNA <50 copies per milliliter, adverse events, disease progression, and death.

RESULTS:

In the on-treatment analysis, the median (interquartile range) increase in the CD4 count after 48 weeks was [phone]) cells per microliter in the efavirenz arm, [phone]) cells per microliter in the ritonavir-boosted atazanavir arm, and [phone]) cells per microliter in the ritonavir-boosted lopinavir arm (P = 0.73). The percentage of patients achieving viral suppression was similar in all 3 treatment arms at 48 weeks {efavirenz, 85.71% [95% confidence interval (CI): 68.5 to 94.3]; atazanavir, 80% [95% CI: 62.7 to 90.5]; and lopinavir, 82.8% [95% CI: 65.5 to 92.4]; P = 0.88}. Bacterial translocation, inflammation, immune activation, and apoptotic markers, but not D-dimer, declined significantly and similarly in the 3 treatment arms. Adverse events had a similar incidence in all 3 antiretroviral regimens. No patients died.

CONCLUSIONS:

The immune reconstitution induced by an efavirenz-based regimen in very advanced HIV-1-infected patients was similar to that induced by a ritonavir-boosted protease inhibitor-based regimen (ClinicalTrials.gov registration number: NCT00532168).

• Authors: Jose M Miro, Christian Manzardo, Elena Ferrer, Montserrat Loncà, Alberto C Guardo, Daniel Podzamczer, Pere Domingo, Adrian Curran, Bonaventura Clotet, Anna Cruceta, Francisco Lozano, Iñaki Pérez, Montserrat Plana, Jose M Gatell, Advanz-3 Study Group
• Journal: Journal of acquired immune deficiency syndromes (1999) (J Acquir Immune Defic Syndr) Vol. 69 Issue 2 Pg. 206-15 (Jun 01 2015) ISSN: 1944-7884 [Electronic] United States
• PMID: 25831464 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Alkynes
• Anti-Retroviral Agents
• Benzoxazines
• Cyclopropanes
• RNA, Viral
• efavirenz
• Ritonavir

Topics

• Adult
• Aged
• Alkynes
• Anti-Retroviral Agents (adverse effects, therapeutic use)
• Antiretroviral Therapy, Highly Active (adverse effects, methods)
• Benzoxazines (adverse effects, therapeutic use)
• CD4 Lymphocyte Count
• Cyclopropanes
• Drug-Related Side Effects and Adverse Reactions (epidemiology, pathology)
• Female
• HIV Infections (drug therapy, immunology)
• HIV-1 (isolation & purification)
• Humans
• Male
• Middle Aged
• Plasma (virology)
• RNA, Viral (blood)
• Ritonavir (adverse effects, therapeutic use)
• Survival Analysis
• Treatment Outcome
• Viral Load
• Young Adult