IDSA Journal Club
- Using Proviral HIV DNA Resistance Assays to Guide Changes in ART
- Duration of Surgical Prophylaxis and Antimicrobial-Associated Adverse Events: Every Day Matters
Did you miss the previous edition of Journal Club? You can find it and other past installments in the IDSA News archives. For a review of other recent research in the infectious diseases literature, see “In the Literature,” by Stanley Deresinski, M.D., FIDSA, in each issue of Clinical Infectious Diseases.
Reviewed by Milana Bogorodskaya, M.D.
Changes in antiretroviral therapy (ART) should be based on prior resistance profiles or ART history in order to ensure effectiveness of the new regimen. However, historical resistance profiles and/or ART regimens are often not available, and an HIV RNA genotype (GT) requires a viral load of > 500 copies/mL. Proviral DNA resistance assays are able to detect HIV DNA in peripheral blood mononuclear cells to identify mutations present.
A single-center study, recently published in Open Forum Infectious Diseases, retrospectively assessed the clinical outcomes and utility of obtaining a DNA GT assay to guide ART regimen changes. A total of 83 people with HIV (8% of all patients seen in clinic) had DNA genotype results available over the 3-year study period, but only 59 changed ART and had adequate follow-up to be included in the analyses. Most were older individuals with > 10-year HIV and ART history. Reasons for ordering a DNA GT included history of being on two or more previous regimens (46%), recent HIV RNA > 50 copies/mL but insufficient for RNA GT (36%), and/or an incomplete ART history (34%). Nine patients had a prior RNA GT for comparison.
In two cases, DNA GT failed to detect M184V mutations identified on RNA GT, and in three cases DNA GT detected resistance-associated mutations that were not detected on prior RNA GT. Pill burden decreased from a mean of 3.48 to 2.05 pills/day (P < 0.001) post ART regimen change. There was no difference in rate of viral load suppression before and after DNA GT testing. There was also no statistically significant change in the probability of an individual having an unsuppressed HIV RNA viral load after a DNA GT-guided ART switch. Four individuals had virologic failure after ART switch, however this was considered to be due to poor adherence because three of the four had follow-up RNA GT with no new detected mutations.
In summary, an HIV DNA genotype assay may be useful in certain situations to assess for archived mutations but is not 100% sensitive in detecting certain mutations such as the M184V.
Reviewed by Daniel Mendoza, M.D., Ph.D.
In a study published in JAMA Surgery, Branch-Elliman et al conducted a multicenter, national retrospective cohort study to determine the benefits and adverse events associated with antimicrobial prophylaxis after surgery. The authors analyzed 79,058 patients undergoing surgical procedures in the Veterans Affairs system, using multivariable logistic regression. Surgeries included orthopedic joint replacement, colorectal, and vascular procedures. The outcome variables were 30-day surgical site infection (SSI), 7-day incidence of acute kidney injury (AKI), and 90-day incidence of C. difficile infection. Patients who were administered β-lactams (predominantly cefazolin) for less than 24 hours were used as the reference group.
Among all patients in the study, 96.3% were male, and the mean age was 64.8 years. After stratification by type of surgery and adjustment for multiple factors (including age, sex, race, diabetes, smoking, methicillin-resistant S. aureus colonization, type of prophylaxis, etc.), SSI was not associated with duration of prophylaxis.
Compared with less than 24 hours of prophylaxis, adjusted odds of AKI increased with each additional day of prophylaxis: cardiac procedure: 24 to < 48 hours: adjusted odds ratio (OR), 1.03 (95% confidence interval [CI], 0.95-1.12); 48 to < 72 hours: OR, 1.22 (95% CI, 1.08-1.39); 72 hours or more: OR, 1.82 [95% CI, 1.54-2.16]; non-cardiac procedure: 24 to < 48 hours: OR, 1.31 (95% CI, 1.21-1.42); 48 to < 72 hours: OR, 1.72 (95% CI, 1.47-2.01); 72 hours: OR, 1.79 (95% CI, 1.27-2.53). C. difficile infection showed a similar duration-dependent association: 24 to < 48 hours: OR, 1.08 (95% CI, 0.89-1.31); 48 to < 72 hours: OR, 2.43 (95% CI, 1.80-3.27); 72 hours or more: OR, 3.65 (95% CI, 2.40-5.53).
The unadjusted numbers needed to harm for AKI after 24 to less than 48 hours, 48 to less than 72 hours, and 72 hours or more of prophylaxis were 9, 6, and 4, respectively; for C. difficile infection these were 2,000, 90, and 50, respectively. Compared with β-lactams, vancomycin was associated with AKI: cardiac procedure: OR, 1.17 (95% CI, 1.10-1.25); non-cardiac procedure: OR, 1.21 (95% CI, 1.13-1.30).
In conclusion, increasing duration of surgical antibiotic prophylaxis was not associated with additional reduction in SSI but it was associated with increasing rates of AKI and C. difficile colitis. Importantly, the risk of adverse events increased with each additional day of antibiotic exposure.