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.
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).


CONCLUSIONS
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.
Department of Nephrology, Charité, University Medicine, Berlin, Germany.
Fabia
F
Zu Knyphausen
Department of Infectious Disease Epidemiology, HIV/AIDS, STI and Blood Born Infections, Robert Koch Institute, Berlin, Germany.
Ramona
R
Scheufele
Department of Infectious Diseases, HIV and Other Retroviruses, Robert Koch Institute, Berlin, Germany.
Claudia
C
Kücherer
Department of Infectious Disease Epidemiology, HIV/AIDS, STI and Blood Born Infections, Robert Koch Institute, Berlin, Germany.
Klaus
K
Jansen
Department of Infectious Diseases, HIV and Other Retroviruses, Robert Koch Institute, Berlin, Germany.
Sybille
S
Somogyi
Medical Care Centre Driesener Strasse, Berlin, Germany.
Stephan
S
Dupke
Medical Care Centre Jessen, Berlin, Germany.
Heiko
H
Jessen
Department of Infectious Diseases and Pulmonary Medicine, Charité, University Medicine, Berlin, Germany.
Dirk
D
Schürmann
Department of Infectious Disease Epidemiology, HIV/AIDS, STI and Blood Born Infections, Robert Koch Institute, Berlin, Germany.
Osamah
O
Hamouda
Department of Infectious Diseases, HIV and Other Retroviruses, Robert Koch Institute, Berlin, Germany.
Karolin
K
Meixenberger
Department of Infectious Disease Epidemiology, HIV/AIDS, STI and Blood Born Infections, Robert Koch Institute, Berlin, Germany.
Barbara
B
Bartmeyer
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000635:transmission / Q000821:virology*; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D008297:Male; D015995:Prevalence; D012307:Risk Factors; D016896:Treatment Outcome; D019562:Viral Load
D019380:Anti-HIV Agents