Ultrasensitive Human Immunodeficiency Virus Type 1 Viral Load as a Marker of Treatment Choice for Simplification Strategies

Clin Infect Dis. 2018 Nov 28;67(12):1883-1889. doi: 10.1093/cid/ciy382.

Abstract

Background: Using 3 randomized Protease inhibitor (PI) monotherapy studies: Kalesolo, Dream and Monoi, we performed a pooled-analysis. Our objective was to determine in PI monotherapy and standard tritherapy: 1) distribution of ultrasensitive viral load (USVL) at week 96 (W96); 2) factors associated with virological failure (VF) at W96 and 3) factors associated with USVL<1 copy at W96.

Methods: VF was defined as 2 consecutive measurements of Human Immunodeficiency Virus Type 1 RNA viral load>50 copies/mL and analysed in Intention-To-Treat. A logistic model was used to investigate which variables were predictive of a VF and Fisher test to investigate differences in USVL at W96.

Results: Among 609 patients, 73% were male with median age of 44.4 years (IQR 39.8-52.1), baseline CD4/CD8 ratio was 0.8 (IQR 0.6-1.10), baseline CD4 was 564.5/mm3 (IQR 422-707) and 59% presented a baseline USVL<1 copy/mL. At W96, the proportion of USVL<1 copy/mL was significantly different between PI monotherapy and standard tritherapy in pooled-analysis (65% versus 74%; p=0.04). Overall, baseline USVL<1copy/mL, tritherapy and to be a female were associated with USVL<1 copy/mL at W96 (p<0.0001, p=0.049 and p=0.006). In PI monotherapy receiving DRV/r was associated with USVL<1 copy/mL at W96 (p=0.003). Factors associated to virological succes at W96 were higher baseline CD4 (p=0.034) and baseline USVL<1 copy/mL (p=0.0005).

Conclusion: Pooled-analysis of 3 PI monotherapy trials showed better efficacy of tritherapy in terms of USVL at W96. Furthermore regarding USVL at W96, to receive LPV/r seems to be more deleterious than DRV/r. Baseline USVL impacts VF at W96 more specifically in tritherapy arm.

Clinical trials registration: NCT00421551, NCT00946595, and NCT00140751.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active / methods*
  • CD4 Lymphocyte Count
  • Darunavir / therapeutic use
  • Data Interpretation, Statistical
  • Female
  • HIV Infections / blood
  • HIV Infections / drug therapy*
  • HIV-1 / isolation & purification
  • Humans
  • Lopinavir / therapeutic use
  • Male
  • Middle Aged
  • RNA, Viral / blood*
  • Ritonavir / therapeutic use
  • Treatment Failure
  • Viral Load*

Substances

  • Anti-HIV Agents
  • RNA, Viral
  • Lopinavir
  • Ritonavir
  • Darunavir

Associated data

  • ClinicalTrials.gov/NCT00421551
  • ClinicalTrials.gov/NCT00946595
  • ClinicalTrials.gov/NCT00140751