Anne Marie O’sUllivan

Background: Mycoplasma genitalium (MG) infection is of public health concern due to antimicrobial resistance (AMR). Data are limited on repeat MG infection and AMR among United States Air Force (USAF) service members (SMs) living with human immunodeficiency virus (HIV). Methods: USAF SMs seeking HIV care were screened for MG infection during the surveillance period (May 16, 2016-March 16, 2020). Baseline and repeat MG prevalence were estimated. An extended Cox proportional hazards regression model evaluated characteristics associated with repeat MG infection. MG-positive rectal samples were tested for macrolide or fluoroquinolone resistance. Results: Among 299 male patients of a total 308 patients followed during the surveillance period, baseline prevalence of MG infection was 19.7% (59/299) and repeat MG was 35% (36/101) among patients who screened positive for MG at any time during the surveillance period. Characteristics independently associated with increased risk of repeat infection were reported prior sexually-transmitted infection (STI) history vs none (adjusted hazards ratio (aHR) 2.21, 95% confidence interval (CI) 1.13-4.35), presence of STI coinfection vs not indicated (aHR 5.13, 95% CI 2.78-9.49), new HIV diagnosis (<1 year vs 1 year or more, aHR 2.63, 95% CI 1.62-4.27). AMR in MG-positive rectal specimens was 88% (43/49) indicating macrolide resistance, 18% (10/56) with quinolone resistance, and 18% (10/56) with both macrolides and fluoroquinolone resistance. Conclusions: Macrolide and fluoroquinolone resistance mutations were common. Testing for co-occurring MG infection and AMR mutations may be warranted in guiding treatment for STIs such as chlamydia or gonorrhea detected at HIV diagnosis.

While large datasets of HIV-1 sequences are increasingly being generated, many studies rely on a single gene or fragment of the genome and few comparative studies across genes have been done. We performed genome-based and gene-specific Bayesian phylogenetic analyses to investigate how certain factors impact estimates of the infection dates in an acute HIV-1 infection cohort, RV217. In this cohort, HIV-1 diagnosis corresponded to the first RNA positive test and occurred a median of four days after the last negative test, allowing us to compare timing estimates using BEAST to a narrow window of infection. We analyzed HIV-1 sequences sampled one week, one month and six months after HIV-1 diagnosis in 39 individuals. We found that shared diversity and temporal signal was limited in acute infection, and insufficient to allow timing inferences in the shortest HIV-1 genes, thus dated phylogenies were primarily analyzed forenv,gag,poland near full-length genomes. There was no one best-fitting model across participants and genes, though relaxed molecular clocks (73% of best-fitting models) and the Bayesian skyline (49%) tended to be favored. For infections with single founders, the infection date was estimated to be around one week pre-diagnosis forenv(IQR: 3–9 days) andgag(IQR: 5–9 days), whilst the genome placed it at a median of 10 days (IQR: 4–19). Multiply-founded infections proved problematic to date. Our ability to compare timing inferences to precise estimates of HIV-1 infection (within a week) highlights that molecular dating methods can be applied to within-host datasets from early infection. Nonetheless, our results also suggest caution when using uniform clock and population models or short genes with limited information content.

Infusion of the broadly neutralizing antibody VRC01 has been evaluated in individuals chronically infected with HIV-1. Here, we studied how VRC01 infusions affected viral rebound after cessation of antiretroviral therapy (ART) in 18 acutely treated and durably suppressed individuals. Viral rebound occurred in all individuals, yet VRC01 infusions modestly delayed rebound and participants who showed a faster decay of VRC01 in serum rebounded more rapidly. Participants with strains most sensitive to VRC01 or with VRC01 epitope motifs similar to known VRC01-susceptible strains rebounded later. Upon rebound, HIV-1 sequences were indistinguishable from those sampled at diagnosis. Across the cohort, participant-derived Env showed different sensitivity to VRC01 neutralization (including 2 resistant viruses), yet neutralization sensitivity was similar at diagnosis and after rebound, indicating the lack of selection for VRC01 resistance during treatment interruption. Our results showed that viremia rebounded despite the absence of HIV-1 adaptation to VRC01 and an average VRC01 trough of 221 μg/mL. Although VRC01 levels were insufficient to prevent a resurgent infection, knowledge that they did not mediate Env mutations in acute-like viruses is relevant for antibody-based strategies in acute infection.