A very low geno2pheno false positive rate is associated with poor viro-immunological response in drug-naïve patients starting a first-line HAART

PLoS One. 2014 Aug 25;9(8):e105853. doi: 10.1371/journal.pone.0105853. eCollection 2014.

Abstract

Background: We previously found that a very low geno2pheno false positive rate (FPR ≤ 2%) defines a viral population associated with low CD4 cell count and the highest amount of X4-quasispecies. In this study, we aimed at evaluating whether FPR ≤ 2% might impact on the viro-immunological response in HIV-1 infected patients starting a first-line HAART.

Methods: The analysis was performed on 305 HIV-1 B subtype infected drug-naïve patients who started their first-line HAART. Baseline FPR (%) values were stratified according to the following ranges: ≤ 2; 2-5; 5-10; 10-20; 20-60; >60. The impact of genotypically-inferred tropism on the time to achieve immunological reconstitution (a CD4 cell count gain from HAART initiation ≥ 150 cells/mm(3)) and on the time to achieve virological success (the first HIV-RNA measurement <50 copies/mL from HAART initiation) was evaluated by survival analyses.

Results: Overall, at therapy start, 27% of patients had FPR ≤ 10 (6%, FPR ≤ 2; 7%, FPR 2-5; 14%, FPR 5-10). By 12 months of therapy the rate of immunological reconstitution was overall 75.5%, and it was significantly lower for FPR ≤ 2 (54.1%) in comparison to other FPR ranks (78.8%, FPR 2-5; 77.5%, FPR 5-10; 71.7%, FPR 10-20; 81.8%, FPR 20-60; 75.1%, FPR >60; p = 0.008). The overall proportion of patients achieving virological success was 95.5% by 12 months of therapy. Multivariable Cox analyses showed that patients having pre-HAART FPR ≤ 2% had a significant lower relative adjusted hazard [95% C.I.] both to achieve immunological reconstitution (0.37 [0.20-0.71], p = 0.003) and to achieve virological success (0.50 [0.26-0.94], p = 0.031) than those with pre-HAART FPR >60%.

Conclusions: Beyond the genotypically-inferred tropism determination, FPR ≤ 2% predicts both a poor immunological reconstitution and a lower virological response in drug-naïve patients who started their first-line therapy. This parameter could be useful to identify patients potentially with less chance of achieving adequate immunological reconstitution and virological undetectability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active
  • CD4 Lymphocyte Count
  • Female
  • Genotype
  • HIV Infections / drug therapy*
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Treatment Outcome*
  • Viral Load

Substances

  • Anti-HIV Agents

Grants and funding

This work was financially supported by the European Commission Framework 7 Programme (CHAIN, the Collaborative HIV and Anti-HIV Drug Resistance Network, Integrated Project no. 223131), and by the European AIDS Treatment Network (NEAT, contract number LSHT/CT/2006/037570); Italian Ministry of Health (CUP: E81J10000000001, Ricerca Corrente and Progetto AIDS grant no. n. 40H78); and by an unrestricted grant from AVIRALIA foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.