Predictors of virological failure in HIV-1-infected patients switching to dolutegravir maintenance monotherapy

Objectives: The Dolutegravir Monotherapy for HIV (DOMONO; NCT02401828) study showed that maintenance monotherapy with dolutegravir (DTG) is associated with virological failure (VF) and leads to DTG resistance and as a result should not be used. However, data on clinical and virological factors associated with VF during DTG monotherapy are lacking. We identified factors associated with VF during DTG monotherapy. Methods: A randomized trial was carried out in which patients on combination antiretroviral therapy (cART) with an HIV-1 RNA zenith < 100 000 copies/mL and a CD4 T-cell nadir ≥ 200 cells/μL, who had never experienced VF, switched to DTG monotherapy. Clinical and virological factors were compared between patients with and without VF, using univariate analyses. Results: Eight of the 95 patients developed VF during DTG monotherapy. A total of 78 participants had reached week 48 when the study was discontinued. The median CD4 T-cell nadir was lower in patients with VF than in patients without VF [260 (interquartile range (IQR) 223–320) versus 380 (IQR 290–520) cells/μL, respectively; P = 0.011]. Patients with VF had a longer time between HIV diagnosis and cART initiation than those without VF [median 49 (IQR 27–64) versus 15 (IQR 1–38) months, respectively; P = 0.015]. The median total peripheral blood mononuclear cell (PBMC) HIV DNA copy number was higher in patients with VF than in those without VF [417 (range 85–4151) versus 147 (range 16–4132) copies/106 PBMCs, respectively; P = 0.022]. Conclusions: A lower CD4 nadir, a longer time between HIV diagnosis and cART initiation, and a higher HIV DNA copy number at the time of DTG monotherapy initiation were associated with VF. While there clearly is no future role for DTG monotherapy, ongoing and future studies on the efficacy of maintenance dual therapy (e.g. DTG lamivudine) may have to take these variables into account in their study design and analysis

Predictors of virological failure in HIV-1-infected patients switching to dolutegravir maintenance monotherapy

Objectives: The Dolutegravir Monotherapy for HIV (DOMONO; NCT02401828) study showed that maintenance monotherapy with dolutegravir (DTG) is associated with virological failure (VF) and leads to DTG resistance and as a result should not be used. However, data on clinical and virological factors associated with VF during DTG monotherapy are lacking. We identified factors associated with VF during DTG monotherapy. Methods: A randomized trial was carried out in which patients on combination antiretroviral therapy (cART) with an HIV-1 RNA zenith < 100 000 copies/mL and a CD4 T-cell nadir ≥ 200 cells/μL, who had never experienced VF, switched to DTG monotherapy. Clinical and virological factors were compared between patients with and without VF, using univariate analyses. Results: Eight of the 95 patients developed VF during DTG monotherapy. A total of 78 participants had reached week 48 when the study was discontinued. The median CD4 T-cell nadir was lower in patients with VF than in patients without VF [260 (interquartile range (IQR) 223–320) versus 380 (IQR 290–520) cells/μL, respectively; P = 0.011]. Patients with VF had a longer time between HIV diagnosis and cART initiation than those without VF [median 49 (IQR 27–64) versus 15 (IQR 1–38) months, respectively; P = 0.015]. The median total peripheral blood mononuclear cell (PBMC) HIV DNA copy number was higher in patients with VF than in those without VF [417 (range 85–4151) versus 147 (range 16–4132) copies/106 PBMCs, respectively; P = 0.022]. Conclusions: A lower CD4 nadir, a longer time between HIV diagnosis and cART initiation, and a higher HIV DNA copy number at the time of DTG monotherapy initiation were associated with VF. While there clearly is no future role for DTG monotherapy, ongoing and future studies on the efficacy of maintenance dual therapy (e.g. DTG lamivudine) may have to take these variables into account in their study design and analysis

Limited cross-border infections in patients newly diagnosed with HIV in Europe

Background: International travel plays a role in the spread of HIV-1 across Europe. It is, however, not known whether international travel is more important for spread of the epidemic as compared to endogenous infections within single countries. In this study, phylogenetic associations among HIV of newly diagnosed patients were determined across Europe.Results: Data came from the SPREAD programme which collects samples of newly diagnosed patients that are representative for national HIV epidemics. 4260 pol sequences from 25 European countries and Israel collected in 2002-2007 were included.We identified 457 clusters including 1330 persons (31.2% of all patients). The cluster size ranged between 2 and 28. A number of 987 patients (74.2%) were part of a cluster that consisted only of patients originating from the same country. In addition, 135 patients (10.2%) were in a cluster including only individuals from neighboring countries. Finally, 208 patients (15.6%) clustered with individuals from countries without a common border. Clustering with patients from the same country was less prevalent in patients being infected with B subtype (P-value &lt;0.0001), in men who have sex with men (P-value &lt;0.0001), and in recently infected patients (P-value =0.045).Conclusions: Our findings indicate that the transmission of HIV-1 in Europe is predominantly occurring between patients from the same country. This could have implications for HIV-1 transmission prevention programmes. Because infections through travelling between countries is not frequently observed it is important to have good surveillance of the national HIV-1 epidemics. © 2013 Frentz et al.; licensee BioMed Central Ltd

Increase in transmitted resistance to non-nucleoside reverse transcriptase inhibitors among newly diagnosed HIV-1 infections in Europe

Background: One out of ten newly diagnosed patients in Europe was infected with a virus carrying a drug resistant mutation. We analysed the patterns over time for transmitted drug resistance mutations (TDRM) using data from the European Spread program.Methods: Clinical, epidemiological and virological data from 4317 patients newly diagnosed with HIV-1 infection between 2002 and 2007 were analysed. Patients were enrolled using a pre-defined sampling strategy.Results: The overall prevalence of TDRM in this period was 8.9% (95% CI: 8.1-9.8). Interestingly, significant changes over time in TDRM caused by the different drug classes were found. Whereas nucleoside resistance mutations remained constant at 5%, a significant decline in protease inhibitors resistance mutations was observed, from 3.9% in 2002 to 1.6% in 2007 (p = 0.001). In contrast, resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) doubled from 2.0% in 2002 to 4.1% in 2007 (p = 0.004) with 58% of viral strains carrying a K103N mutation. Phylogenetic analysis showed that these temporal changes could not be explained by large clusters of TDRM.Conclusion: During the years 2002 to 2007 transmitted resistance to NNRTI has doubled to 4% in Europe. The frequent use of NNRTI in first-line regimens and the clinical impact of NNRTI mutations warrants continued monitoring. © 2014 Frentz et al.; licensee BioMed Central Ltd