No abstract

Although resistance to tigecycline has been reported in surveillance studies, very few reports have described the emergence of resistance in vivo. We report two cases of patients with infections due to SHV-12-producing Klebsiella pneumoniae and K. pneumoniae carbapenemase-3 (KPC-3)-producing Escherichia coli, which developed tigecycline resistance in vivo after treatment. The reported limited experience underlines the risk of occurrence of a tigecycline MIC increase under treatment pressure.

Abstract Background Prevalence of potential drug-drug interactions (PDDIs) between antiretroviral drugs (ARVs) and comedications was high in 2008 in a Swiss HIV Cohort Study (SHCS) survey. We reassessed the prevalence of PDDIs in the era of HIV integrase inhibitors (INIs), characterized by more favorable interaction profiles. Methods The prevalence of PDDIs in treated HIV positive individuals was assessed for the period: 01-12/2018 by linkage of the Liverpool HIV drug interactions and SHCS databases. PDDIs were categorized as harmful (red flagged), of potential clinical relevance (amber flagged) or of weak clinical significance (yellow flagged). Results In 9’298 included individuals, median age was 51 years (IQR 43; 58), and 72% were males. Individuals received unboosted INIs (40%), boosted ARVs (30%), and non-nucleoside reverse transcriptase inhibitors (NNRTIs) (32%) based regimens. In the entire cohort, 68% received > 1 comedication, 14% had polypharmacy (> 5 comedications) and 29% had > 1 PDDI. Among individuals with comedication, the prevalence of combined amber and yellow PDDIs was 43% (33% amber - mostly with cardiovascular drugs - and 20% yellow flagged PDDIs) compared to 59% in 2008. Two percent had red flagged PDDIs (mostly with corticosteroids), the same as in the 2008 survey. Compared to 2008, fewer individuals received boosted ARVs (-24%) and NNRTIs (-13%) but the use of comedications was higher. Conclusions Prevalence of PDDIs was lower with more widespread use of INIs in 2018 than in 2008. Continued use of boosted regimens and increasing needs for comedications in this aging population impeded lower rates of PDDIs.

No abstract

The aim of this proof-of-concept study is to test feasibility and efficacy of NVP plus Lamivudine (3TC) as novel simplified HIV maintenance dual therapy (DT) strategy. Methods Patients under combined antiretroviral treatment (cART) with fully suppressed HIV plasma viral load (pVL) >24 months-whereof >6 months on an NVP-containing regimen-were switched to oral NVP plus 3TC for 24 weeks. Patients could then decide whether to continue DT or return to the previous cART. HIV pVL was monitored monthly until week 144. The primary outcome was confirmed viral failure (RNA >100 copies/ml). Low-level detection of HIV-RNA in plasma was compared in each patient with pre-study viral load measurements. Results Twenty patients were included, switched to DT and all completed week 24. One patient decided thereafter to discontinue study participation for personal reasons. After a total of 144 observation weeks, none of the patients failed. The frequency of low-level HIV-RNA detection was not different from the period before randomization. Conclusions Our findings are surprising but given the nature of a proof-of-concept study, the results do not support the use of this dual regimen. However, as this dual HIV maintenance strategy was feasible and effective, over a period of 144 weeks, we suggest NVP plus 3TC warrants further evaluation as potential maintenance option in patients tolerating nevirapine. A properly sized multicentre non-inferiority trial is ongoing to further evaluate the value of this DT maintenance strategy.