First line treatment response in patients with transmitted HIV drug resistance and well defined time point of HIV infection: updated results from the German HIV-1 seroconverter study

PLoS One. 2014 May 1;9(5):e95956. doi: 10.1371/journal.pone.0095956. eCollection 2014.

Abstract

Background: Transmission of drug-resistant HIV-1 (TDR) can impair the virologic response to antiretroviral combination therapy. Aim of the study was to assess the impact of TDR on treatment success of resistance test-guided first-line therapy in the German HIV-1 Seroconverter Cohort for patients infected with HIV between 1996 and 2010. An update of the prevalence of TDR and trend over time was performed.

Methods: Data of 1,667 HIV-infected individuals who seroconverted between 1996 and 2010 were analysed. The WHO drug resistance mutations list was used to identify resistance-associated HIV mutations in drug-naïve patients for epidemiological analysis. For treatment success analysis the Stanford algorithm was used to classify a subset of 323 drug-naïve genotyped patients who received a first-line cART into three resistance groups: patients without TDR, patients with TDR and fully active cART and patients with TDR and non-fully active cART. The frequency of virologic failure 5 to 12 months after treatment initiation was determined.

Results: Prevalence of TDR was stable at a high mean level of 11.9% (198/1,667) in the HIV-1 Seroconverter Cohort without significant trend over time. Nucleotide reverse transcriptase inhibitor resistance was predominant (6.0%) and decreased significantly over time (OR = 0.92, CI = 0.87-0.98, p = 0.01). Non-nucleoside reverse transcriptase inhibitor (2.4%; OR = 1.00, CI = 0.92-1.09, p = 0.96) and protease inhibitor resistance (2.0%; OR = 0.94, CI = 0.861.03, p = 0.17) remained stable. Virologic failure was observed in 6.5% of patients with TDR receiving fully active cART, 5,6% of patients with TDR receiving non-fully active cART and 3.2% of patients without TDR. The difference between the three groups was not significant (p = 0.41).

Conclusion: Overall prevalence of TDR remained stable at a rather high level. No significant differences in the frequency of virologic failure were identified during first-line cART between patients with TDR and fully-active cART, patients with TDR and non-fully active cART and patients without TDR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active
  • CD4 Lymphocyte Count
  • Drug Resistance, Viral*
  • Female
  • Genotype
  • HIV Infections / drug therapy*
  • HIV Infections / epidemiology
  • HIV Infections / transmission
  • HIV Infections / virology*
  • HIV-1* / genetics
  • Humans
  • Male
  • Prevalence
  • Risk Factors
  • Treatment Outcome
  • Viral Load

Substances

  • Anti-HIV Agents

Grants and funding

The study was funded by a grant of the German Ministry of Health. The HIV-1 serooconverter cohort is conducted by the Robert Koch-Institute which is the German public health institute. The grant number is 83–917. The URL of the funding ministry of health is: http://www.bmg.bund.de/praevention/gesundheitsgefahren/hivaids.html. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.