Minority variant human immunodeficiency virus type 1 (HIV-1) nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations are associated with an increased risk of virological failure during treatment with NNRTI-containing regimens. To determine whether individuals to whom variants with isolated NNRTI-associated drug resistance were transmitted are at increased risk of virological failure during treatment with a non-NNRTI–containing regimen, we identified minority variant resistance mutations in 33 individuals with isolated NNRTI-associated transmitted drug resistance and 49 matched controls. We found similar proportions of overall and nucleoside reverse transcriptase inhibitor–associated minority variant resistance mutations in both groups, suggesting that isolated NNRTI-associated transmitted drug resistance may not be a risk factor for virological failure during treatment with a non-NNRTI–containing regimen.

A hybridization-based point-of-care (POC) assay for HIV-1 drug resistance would be useful in low- and middle-income countries (LMICs) where resistance testing is not routinely available. The major obstacle in developing such an assay is the extreme genetic variability of HIV-1. We analyzed 27,203 reverse transcriptase (RT) sequences from the Stanford HIV Drug Resistance Database originating from six LMIC regions. We characterized the variability in a 27-nucleotide window surrounding six clinically important drug resistance mutations (DRMs) at positions 65, 103, 106, 181, 184, and 190. The number of distinct codons at each DRM position ranged from four at position 184 to 11 at position 190. Depending on the mutation, between 11 and 15 of the 24 flanking nucleotide positions were variable. Nonetheless, most flanking sequences differed from a core set of 10 flanking sequences by just one or two nucleotides. Flanking sequence variability was also lower in each LMIC region compared with overall variability in all regions. We also describe an online program that we developed to perform similar analyses for mutations at any position in RT, protease, or integrase.

Data guiding the duration and route of streptococcal bloodstream infection (BSI) treatment are lacking. We conducted a retrospective cohort study of adults hospitalized with uncomplicated streptococcal BSI in a large integrated healthcare system from 2013 to 2020. The exposures of interest were antibiotic duration (5–10 days vs. 11–15 days) and antibiotic route (oral switch vs. entirely intravenous). The primary outcome was a composite 90-day outcome comprised of all-cause mortality, recurrent streptococcal BSI, or readmission. We performed non-inferiority analyses for each exposure. Separate multivariable Cox proportional hazards regression models were constructed for each exposure. The antibiotic duration analysis included 1,407 patients (5–10 days, n = 246; 11–15 days, n = 1,161). We found that 5–10-day courses were non-inferior to 11–15-day courses ( P = 0.047). The antibiotic route analysis included 1,461 patients (oral switch, n = 1,112; entirely intravenous, n = 349). Oral step-down therapy did not meet the criteria for non-inferiority ( P = 0.06). In the adjusted models, no significant difference was found in the primary outcome rate by antibiotic duration or antibiotic route at discharge. We found that 5–10-day courses were non-inferior to longer courses, and thus may be a safe and effective treatment option in the treatment of uncomplicated streptococcal bacteremia. Randomized controlled trials are needed to confirm the equivalent outcomes with shorter regimens and to definitively determine the optimal antibiotic route on discharge.

Background: Nonnucleoside reverse transcriptase inhibitor (NNRTI)–associated transmitted drug resistance (TDR) is the most common type of TDR. Few data guide the selection of antiretroviral therapy (ART) for patients with such resistance. Methods: We reviewed treatment outcomes in a cohort of HIV-1–infected patients with isolated NNRTI TDR who initiated ART between April 2002 and May 2014. In an as-treated analysis, virological failure (VF) was defined as not reaching undetectable virus levels within 24 weeks, virological rebound, or switching regimens during viremia. In an intention-to-treat analysis, failure was defined more broadly as VF, loss to follow-up, and switching during virological suppression. Results: Of 3245 patients, 131 (4.0%) had isolated NNRTI TDR; 122 received a standard regimen comprising 2 NRTIs plus a boosted protease inhibitor (bPI; n = 54), an integrase strand transfer inhibitor (INSTI; n = 52), or an NNRTI (n = 16). The median follow-up was 100 weeks. In the as-treated analysis, VF occurred in 15% (n = 8), 2% (n = 1), and 25% (n = 4) of patients in the bPI, INSTI, and NNRTI groups, respectively. In multivariate regression, there was a trend toward a lower risk of VF with INSTIs than with bPIs (hazard ratio: 0.14; 95% confidence interval: 0.02 to 1.1; P = 0.07). In intention-to-treat multivariate regression, INSTIs had a lower risk of failure than bPIs (hazard ratio: 0.38; 95% confidence interval: 0.18 to 0.82; P = 0.01). Conclusions: Patients with isolated NNRTI TDR experienced low VF rates with INSTIs and bPIs. INSTIs were noninferior to bPIs in an analysis of VF but superior to bPIs when frequency of switching and loss to follow-up were also considered.