Prevalence of Transmitted Drug Resistance and Impact of Transmitted Resistance on Treatment Success in the German HIV-1 Seroconverter Cohort

BACKGROUND: The aim of this study is to analyse the prevalence of transmitted drug resistance, TDR, and the impact of TDR on treatment success in the German HIV-1 Seroconverter Cohort. METHODS: Genotypic resistance analysis was performed in treatment-naïve study patients whose sample was available 1,312/1,564 (83.9% October 2008). A genotypic resistance result was obtained for 1,276/1,312 (97.3%). The resistance associated mutations were identified according to the surveillance drug resistance mutations list recommended for drug-naïve patients. Treatment success was determined as viral suppression below 500 copies/ml. RESULTS: Prevalence of TDR was stable at a high level between 1996 and 2007 in the German HIV-1 Seroconverter Cohort (N = 158/1,276; 12.4%; CI(wilson) 10.7-14.3; p(for trend) = 0.25). NRTI resistance was predominant (7.5%) but decreased significantly over time (CI(Wilson): 6.2-9.1, p(for trend) = 0.02). NNRTI resistance tended to increase over time (NNRTI: 3.5%; CI(Wilson): 2.6-4.6; p(for trend)= 0.07), whereas PI resistance remained stable (PI: 3.0%; CI(Wilson): 2.1-4.0; p(for trend) = 0.24). Resistance to all drug classes was frequently caused by singleton resistance mutations (NRTI 55.6%, PI 68.4%, NNRTI 99.1%). The majority of NRTI-resistant strains (79.8%) carried resistance-associated mutations selected by the thymidine analogues zidovudine and stavudine. Preferably 2NRTI/1PIr combinations were prescribed as first line regimen in patients with resistant HIV as well as in patients with susceptible strains (susceptible 45.3%; 173/382 vs. resistant 65.5%; 40/61). The majority of patients in both groups were treated successfully within the first year after ART-initiation (susceptible: 89.9%; 62/69; resistant: 7/9; 77.8%). CONCLUSION: Overall prevalence of TDR remained stable at a high level but trends of resistance against drug classes differed over time. The significant decrease of NRTI-resistance in patients newly infected with HIV might be related to the introduction of novel antiretroviral drugs and a wider use of genotypic resistance analysis prior to treatment initiation

Torque Teno Virus plasma level as novel biomarker of retained immunocompetence in HIV-infected patients

Purpose To predict the course of immune recovery (IR) in HIV-1-infected patients after initiation of combined antiretroviral therapy (cART) by determination of the plasma concentration of Torque Teno Virus (TTV). TTV has been identified as marker for risk assessment in immunosuppressed patients after transplantation procedures. Here, TTV was analyzed in HIV-1-infected therapy-naive patients to evaluate its use as predictor of the course of IR for guidance of individualized treatment. Methods TTV DNA was quantified in plasma samples of 301 therapy-naive HIV-1-infected patients and correlated to CD4(+) cell count, HIV viral load, presence of the herpes viruses CMV, EBV and HHV-8, age and sex. Patients were classified according to their initial CD4(+) cell count and to the extent of CD4(+) T-cell increase within the first year of cART. Results TTV DNA was detectable in 96% of the patients' plasma samples with a median TTV plasma concentration of 5.37 log(10) cop/ml. The baseline CD4(+) cell count was negatively correlated with TTV plasma concentration (p = 0.003). In patients with a CD4(+) cell recovery 200 CD4(+) cells/mu l (5.68 log(10) cop/ml versus 4.99 log(10) cop/ml; p = 0.011). TTV plasma concentration in combination with baseline CD4(+) cell count were significantly correlated to CD4(+) cell recovery (p = 0.004). For all other parameters considered, no significant correlation for CD4(+) cell recovery was found. Conclusion Within the cohort, the significantly elevated TTV plasma concentration in patients with diminished CD4(+) cell recovery indicates a more profound immune defect. Baseline TTV plasma concentrations and CD4(+) cell count are predictive for the course of immune recovery in HIV-1-infected patients with severe immunodeficiency