HIV and ID Observations

National Association for the Prevention of Tuberculosis, 1910.

There’s so much out there right now on COVID-19 (the disease) and SARS-CoV-2 (the virus) that the other ID news gets crowded out.

Which means it’s time for non-COVID-19 ID/HIV Link-o-Rama! I haven’t done one of these in a while, so there’s plenty of material in the vaults yearning to be free.

• The CDC now recommends short-course, rifamycin-based, 3- or 4-month latent TB infection treatments as preferred over 9 months of isoniazid. Completely agree, as 3 or 4 months seems so much shorter than 9 months. Important reminder — watch for rifampin-related drug interactions! Will the 1 month of rifapentine plus isoniazid regimen be in the next version of these guidelines?
• Among patients with MRSA bacteremia, addition of an antistaphylococcal β-lactam to standard antibiotic therapy with vancomycin or daptomycin did not overall improve outcomes. While persistent bacteremia was numerically reduced with combination therapy, vancomycin plus an antistaphylococcal penicillin led to a higher rate of renal injury, prompting the DSMB to stop the study early. This safety issue was not observed with cefazolin, so vancomycin plus cefazolin is still being studied in a separate trial. Excellent summary from the lead author Steven Tong here.
• Ceftaroline plus daptomycin combination therapy may reduce mortality in patients with MRSA bacteremia. This retrospective, matched cohort study supplements favorable findings on this combination from an earlier, small, randomized trial. Some appropriately cautionary commentary from the lead author Erin McReary here. Unfortunately, it does not appear that a randomized study of this combination is in the works due to the cost of the drugs and lack of interest from the manufacturers. Let’s continue the staph bacteremia theme but move on to MSSA with …
• Cefazolin and ertapenem appear to rapidly clear persistent MSSA bacteremia. This uncontrolled study describes 11 patients for whom this combination treatment quickly cleared blood cultures. The authors postulate that ertapenem “rescues” the relatively attenuated activity of cefazolin against MSSA, noting that certain microenvironments (such as bacterial endocarditis vegetations) might make this reduced activity clinically relevant. That’s enough Staph bacteremia for now!
• The latest DHHS HIV guidelines have added dolutegravir (DTG) plus lamivudine (3TC) as a recommended initial regimen. This is the first time a two-drug regimen has garnered this status. Appropriately, there is accompanying cautionary language about excluding baseline HIV RNA > 500,000, chronic hepatitis B, and transmitted M184V. With the encouraging data on this highly effective two-drug regimen, I ask — what’s the purpose of abacavir/3TC/DTG, which is also still listed?
• The TANGO study showed that people with viral suppression on tenofovir alafenamide (TAF)-based treatments can safely switch to DTG/3TC. Switch strategies will likey account for most of the use of this DTG/3TC regimen, since for initial treatment, it’s still easier to go with TAF/FTC/BIC or TAF/FTC plus DTG (no need to know baseline viral load, resistance, or hepatitis B status). And another dance-named study — SALSA — will expand this switch population to anyone who doesn’t have resistance to either 3TC or DTG (no baseline TAF regimen required). No reason why the results of SALSA will be any different than TANGO, but of course surprising things do happen. And no, I don’t know what either of these acronyms stands for.
• The cost of antiretroviral therapy in the United States is high — and increasing faster than the rate of inflation. In 2012, the yearly average wholesale price for recommended initial regimens was $25,000 to $35,000, increasing to $36,000 to $48,000 in 2018. While hardly anyone pays this full price due to insurance, the AIDS Drug Assistance Program (ADAP), patient assistance programs, and other funding mechanisms, even paying part represents real hardship for some patients — especially concerning since high out-of-pocket costs negatively impact adherence.
• Immunization for zoster may reduce the risk of stroke. In a review of Medicare data, receipt of the live zoster vaccine was associated with a 20% reduction in the risk of stroke for those younger than 80. Note that the data analyzed preceded the availability of the recombinant zoster vaccine, which is more effective in preventing shingles than the live version. Since zoster is a potential trigger of stroke, would we see an even greater decline in stroke incidence with the newer vaccine? A compelling additional motivation for immunization.
• Roughly $42 million was spent responding to measles outbreaks in 2019 alone. In addition to the huge cost of controlling these outbreaks, there is also the opportunity cost for public health departments and their staff — who have plenty of other work to do. So annoying.
• Another state has a bill to eliminate “religious” exemptions for vaccines. Strongly support these bills! These non-medical exemptions for children are particularly insidious, as clinicians out of respect may not want to question patient preferences based on religious beliefs. But the reality is that no mainstream religion actually prohibits vaccinations, which is why I put “religious” in quotes.
• The Advisory Committee on Immunization Practices (ACIP) released its 2020 Adult Immunization Schedule. As anticipated, they formally endorse some changes hinted at previously — notably no longer recommending pneumococcal 13-valent conjugate vaccine (PCV-13) for all adults older than 65 (“consider” based on preference), and supporting the HPV vaccine up to age 45 if patients have ongoing risk for new infection.
• Approximately 8% of mycoplasma isolates in the United States have evidence of resistance to macrolides. Difficult to estimate the clinical implications of this resistance, since we rarely isolate mycoplasma in clinical practice and such testing is only available in research laboratories. Regardless, fluoroquinolones and doxycycline likely retain activity, along with the recently approved drug lefamulin — an antibiotic I still haven’t had the opportunity (or cause) to use.
• Here’s a mega-review of investigational antifungal agents. Rezafungin, ibrexafungerp, olorofim, fosmanogepix, et. al. — the gang’s all here! An incredibly useful paper, especially for those of us not actively involved in antifungal research.
• In a retrospective, multicenter, cohort study done in the VA system, empiric anti-MRSA therapy for patients hospitalized for pneumonia was associated with worse clinical outcomes — even in those at risk for MRSA. By using some serious statistical gymnastics, the investigators examined data from 89,000 admissions to emulate a clinical trial result. Can you say “inverse probability of treatment–weighted propensity score analysis using generalized estimating equation regression” and explain it, please? Still, it’s another cautionary note about unnecessary broad-spectrum therapy and a real boost to antimicrobial stewardship efforts to stop empiric vancomycin.
• Dr. Aditya Shah, an ID Fellow at Mayo Clinic, continues to make us laugh. How about this one from last week?

When the attending supervises the procedure you are doing #stewardmeme pic.twitter.com/WqEIaJ2W8O

— Aditya Shah (@IDdocAdi) February 16, 2020

Adi was kind enough to join me on an OFID podcast to discuss what motivates and inspires him to post these memes — highly recommended!