To estimate the extent of drug resistance accumulation in patients kept on a virologically failing regimen and its determinants in the clinical setting. The study focused on 110 patients of EuroSIDA on an unchanged regimen who had two genotypic tests performed at two time points (t0 and t1) when viral load was > 400 copies/ml. Accumulation of resistance between t0 and t1 was measured using genotypic susceptibility scores (GSS) obtained by counting the total number of active drugs (according to the Rega system v6.4.1) among all licensed antiretrovirals as of 1 January 2006. Patients were grouped according to the number of active drugs in the failing regimen at t0 (GSS_f-t0). At t0, patients had been on the failing combination antiretroviral therapy (cART) for a median of 11 months (range, 6-50 months). Even patients with extensive resistance to the failing regimen were still receiving benefit from treatment. An overall 6-monthly increase of 1.96 (SD, 2.23) International Aids Society-mutations and an average loss of 1.25 (SD, 1.81) active drugs were estimated. In comparison with patients with GSS_f-t0 = 0, the number of active drugs lost was -1.08 [95% confidence interval (CI), -2.13 to -0.03; P = 0.04] in those with GSS_f-t0 of 0.5-1.5 and -1.24 (95% CI, -2.44 to -0.04; P = 0.04) in those with GSS_f-t0 >or= 2. In patients kept on the same virologically failing cART regimen for a median of 6 months, there was considerable accumulation of drug resistance mutations, particularly in patients with initial low level of resistance to the failing regimen. Randomized comparisons of maintenance treatment strategies while awaiting a new suppressive therapy to become available are warranted.

Frequency of active human herpesvirus-6, -7 (HHV-6, HHV-7) and parvovirus B19 (B19) infection/coinfection and its association with clinical course of ME/CFS was evaluated. 108 ME/CFS patients and 90 practically healthy persons were enrolled in the study. Viral genomic sequences were detected by PCR, virus-specific antibodies and cytokine levels—by ELISA, HHV-6 variants—by restriction analysis. Active viral infection including concurrent infection was found in 64.8% (70/108) of patients and in 13.3% (12/90) of practically healthy persons. Increase in peripheral blood leukocyte DNA HHV-6 load as well as in proinflammatory cytokines' levels was detected in patients during active viral infection. Definite relationship was observed between active betaherpesvirus infection and subfebrility, lymphadenopathy and malaise after exertion, and between active B19 infection and multijoint pain. Neuropsychological disturbances were detected in all patients. The manifestation of symptoms was of more frequent occurrence in patients with concurrent infection. The high rate of active HHV-6, HHV-7 and B19 infection/coinfection with the simultaneous increase in plasma proinflammatory cytokines' level as well as the association between active viral infection and distinctive types of clinical symptoms shows necessity of simultaneous study of these viral infections for identification of possible subsets of ME/CFS.

Low adherence and toxicities among HIV-positive patients starting highly active antiretroviral therapy (HAART) can lead to discontinuation of therapy and treatment failure. Little is known about hepatitis C (HCV) status and discontinuation of HAART. Poisson regression was used to determine factors related to discontinuation of any part of an initial HAART regimen due to treatment failure (TF) or toxicities and patient/ physician choice (TOX), and to investigate the relationship between HCV and discontinuation of a HAART regimen in 1198 patients staring HAART after 1999 from the EuroSIDA study. At 1 year after starting HAART, 70% of patients remained on their original regimen, 24% had changed, and 6% were off all treatment. The most frequent reason for discontinuation was toxicities (30.4%). There was no change over time in the proportion of patients discontinuing after stratification by reason for discontinuation (p = 0.18). Of patients 190 stopped at least one antiretroviral drug used in their initial HAART regimen due to toxicities; the toxicity reported did not vary according to HCV status (p = 0.90). Anti-HCV seropositive patients had a higher incidence of discontinuation due to TOX (IRR 1.46, 95% CI 1.13–1.88, p = 0.0042) compared to patients without HCV. Patients with HCV were more likely to discontinue all or part of their HAART regimens due to toxicity or patient/physician choice. Managing adverse events must remain a key intervention in maintaining HAART. There is a need for further studies to describe the relationship between HCV, specific antiretrovirals, and different treatment strategies.

Low adherence and toxicities among HIV-positive patients starting highly active antiretroviral therapy (HAART) can lead to discontinuation of therapy and treatment failure. Little is known about hepatitis C (HCV) status and discontinuation of HAART. Poisson regression was used to determine factors related to discontinuation of any part of an initial HAART regimen due to treatment failure (TF) or toxicities and patient/ physician choice (TOX), and to investigate the relationship between HCV and discontinuation of a HAART regimen in 1198 patients staring HAART after 1999 from the EuroSIDA study. At 1 year after starting HAART, 70% of patients remained on their original regimen, 24% had changed, and 6% were off all treatment. The most frequent reason for discontinuation was toxicities (30.4%). The incidence of any discontinuation was significantly lower after 1999 compared to before [incidence rate ratio (IRR) 0.43; 95% CI 0.35–0.53, p < 0.0001], this pattern was most marked for toxicities (IRR 0.28; 95% CI 0.20–0.39, p < 0.0001) and patient/physician choice (IRR 0.49; 95% CI 0.33–0.73, p < 0.0001). Patients with HCV had a higher incidence of discontinuation due to TOX (IRR 1.46, 95% CI 1.13–1.88, p = 0.0042) compared to patients without HCV. Patients with HCV were more likely to discontinue all or part of their HAART regimens due to toxicity or patient/physician choice. Managing adverse events must remain a key intervention in maintaining HAART. There is a need for further studies to describe the relationship between HCV, specific antiretrovirals, and different treatment strategies.