Background. The pilot phase IIb VIKING study suggested that dolutegravir (DTG), a human immunodeficiency virus (HIV) integrase inhibitor (INI), would be efficacious in INI-resistant patients at the 50 mg twice daily (BID) dose.Methods. VIKING-3 is a single-arm, open-label phase III study in which therapy-experienced adults with INI-resistant virus received DTG 50 mg BID while continuing their failing regimen (without raltegravir or elvitegravir) through day 7, after which the regimen was optimized with ≥1 fully active drug and DTG continued. The primary efficacy endpoints were the mean change from baseline in plasma HIV-1 RNA at day 8 and the proportion of subjects with HIV-1 RNA <50 c/mL at week 24.Results. Mean change in HIV-1 RNA at day 8 was −1.43 log10 c/mL, and 69% of subjects achieved <50 c/mL at week 24. Multivariate analyses demonstrated a strong association between baseline DTG susceptibility and response. Response was most reduced in subjects with Q148 + ≥2 resistance-associated mutations. DTG 50 mg BID had a low (3%) discontinuation rate due to adverse events, similar to INI-naive subjects receiving DTG 50 mg once daily.Conclusions. DTG 50 mg BID–based therapy was effective in this highly treatment-experienced population with INI-resistant virus.Clinical Trials Registration. (NCT01328041) and (112574).
Seventy-seven cases of bacteremia due to Achromobacter xylosoxidans were reviewed, and susceptibility studies were performed on 11 clinical isolates of A. xylosoxidans. Nosocomial bacteremia was noted in 54 of 77 patients (70%), and 28 (36%) had infection associated with an outbreak or acquired from a discrete point source. The most common underlying illnesses were malignancies (30%) and cardiac disease (21%); immunosuppression affected 27%. The most common clinical syndromes were primary and catheter-associated bacteremia (19% each) and pneumonia (16%). The case-fatality rate was 30%; only 3% of patients with primary or catheter-associated bacteremia died, but 65% of patients with meningitis, endocarditis, and pneumonia died. The case-fatality rate in neonates was 80%. Susceptibility studies showed that all strains were resistant to aminoglycosides, most were resistant to quinolones, and all were susceptible to broad-spectrum penicillins, imipenem, ceftazidime, and trimethoprim-sulfamethoxazole. Two-disk approximation and time-kill studies showed synergy or additive effects for the combination of gentamicin and piperacillin against most strains.
The efficacy of tocilizumab (TOC), monoclonal antibody against interleukin‐6 (IL‐6) receptor, in patients with coronavirus disease‐2019 (COVID‐19) patients has led to conflicting results. We performed a systematic review and meta‐analysis to compare the efficacy of addition of TOC to standard of care (SOC) versus SOC in patients with COVID‐19. We performed a comprehensive literature search of PubMed, Embase, Web of Science, WHO COVID, LitCOVID, and Cochrane databases. Pooled outcomes (overall mortality, need for mechanical ventilation, intensive care unit admission, and secondary infections) were compared using DerSimonian‐Laird/Random‐effects approach. Risk difference (RD), confidence interval (CI), and p values were generated. A total of 23 studies with 6279 patients (1897 in TOC and 4382 in SOC group, respectively) were included. The overall mortality was lower in TOC group compared to SOC group (RD: −0.06; CI: −0.12 to −0.01; p = .03). Subgroup analysis including studies with only severe cases revealed lower mortality (RD: −0.12; CI: −0.18 to −0.06; p < .01) and need for mechanical ventilation (RD: −0.11; CI: −0.19 to −0.02; p = .01) in TOC group compared to SOC group. The addition of TOC to SOC has the potential to reduce mortality and need for mechanical ventilation in patients with severe COVID‐19. Randomized controlled trials are needed to validate this.
The use of complementary and alternative medicine (CAM) therapies is widespread in many chronic illnesses, including human immunodeficiency virus (HIV) infection. The objective of this study was to determine the impact of increasingly effective antiretroviral therapy on the use of CAM in an HIV-positive patient population. A written survey was given to 191 HIV-positive outpatients. Participation was voluntary and anonymous. One hundred twenty-eight patients (67%) used CAM at some time to control HIV and 76 (40%) of the patients were currently using CAM. The major forms of CAM used were exercise (43%), lifestyle changes (38%), dietary supplements (37%), counseling (27%), herbal medications (26%), megavitamins (24%), and prayer therapy (24%). One hundred forty-one patients (74%) used a protease inhibitor medication, 28 (15%) used a protease inhibitor sparing regime, and 22 (11%) had no current or prior antiretroviral use. Eighty-two (43%) patients indicated that their doctor knew they used CAM and 56 patients (29%) received their information about CAM from a doctor or other health care professional. Of 128 patients who used CAM, 90 (70%) felt CAM improved their quality of life. Income of $15,000 or more per year and discontinuation of medications by patients for any reason in the past were the best predicators of CAM use for patients in general and also those on protease inhibitor therapy. CD(4) count, educational status, year of HIV diagnosis, and martial status were not effective predictors of CAM use. Use of CAM remains widespread among patients with HIV infection even with the availability of effective, yet noncurative antiretroviral therapy and does not correlate with type of antiretroviral therapy used or clinical status.
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