Persistence of HIV transmission clusters among people who inject drugs.

OBJECTIVE: We investigated the duration of HIV transmission clusters. DESIGN: Fifty-four individuals newly infected at enrollment in the ALIVE cohort were included, all of whom had sequences at an intake visit (T1) and from a second (T2) and/or a third (T3) follow-up visit, median 2.9 and 5.4 years later, respectively. METHODS: Sequences were generated using the 454 DNA sequencing platform for portions of HIV pol and env (HXB2 positions 2717-3230; 7941-8264). Genetic distances were calculated using tn93 and sequences were clustered over a range of thresholds (1--5%) using HIV-TRACE. Analyses were performed separately for individuals with pol sequences for T1 + T2 (n = 40, 'Set 1') and T1 + T3 (n = 25; 'Set 2'), and env sequences for T1 + T2 (n = 47, 'Set 1'), and T1 + T3 (n = 30; 'Set 2'). RESULTS: For pol, with one exception, a single cluster contained more than 75% of samples at all thresholds, and cluster composition was at least 90% concordant between time points/thresholds. For env, two major clusters (A and B) were observed at T1 and T2/T3, although cluster composition concordance between time points/thresholds was low (<60%) at lower thresholds for both sets 1 and 2. In addition, several individuals were included in clusters at T2/T3, although not at T1. CONCLUSION: Caution should be used in applying a single threshold in population studies where seroconversion dates are unknown. However, the retention of some clusters even after 5 + years is evidence for the robustness of the clustering approach in general.

Antibody avidity-based approach to estimate population-level incidence of hepatitis C.

BACKGROUND & AIMS: Accurate HCV incidence estimates are critical for monitoring progress towards HCV elimination goals, including an 80% reduction in HCV incidence by 2030. Moreover, incidence estimates can help guide prevention and treatment programming, particularly in the context of the US opioid epidemic. METHODS: An inexpensive, Genedia-based HCV IgG antibody avidity assay was evaluated as a platform to estimate cross-sectional, population-level primary HCV incidence using 1,840 HCV antibody and RNA-positive samples from 875 individuals enrolled in 5 cohort studies in the US and India. Using samples collected <2 years following HCV seroconversion, the mean duration of recent infection (MDRI) was calculated by fitting a maximum likelihood binomial regression model to the probability of appearing recent. Among samples collected ≥2 years post-HCV seroconversion, an individual-level false recent ratio (FRR) was calculated by estimating the probability of appearing recent using an exact binomial test. Factors associated with falsely appearing recent among samples collected ≥2 years post seroconversion were determined by Poisson regression with generalized estimating equations and robust variance estimators. RESULTS: An avidity index cut-off of <40% resulted in an MDRI of 113 days (95% CI 84-146), and FRRs of 0.4% (95% CI 0.0-1.2), 4.6% (95% CI 2.2-8.3), and 9.5% (95% CI 3.6-19.6) among individuals who were HIV-uninfected, HIV-infected, and HIV-infected with a CD4 count <200/µl, respectively. No variation was seen between HCV genotypes 1 and 3. In hypothetical scenarios of high-risk settings, a sample size of <1,000 individuals could reliably estimate primary HCV incidence. CONCLUSIONS: This cross-sectional approach can estimate primary HCV incidence for the most common genotypes. This tool can serve as a valuable resource for program and policy planners seeking to monitor and reduce HCV burden. LAY SUMMARY: Determining the rate of new hepatitis C virus (HCV) infections in a population is critical to monitoring progress toward HCV elimination and to appropriately guide control efforts. However, since HCV infections are most often initially asymptomatic, it is difficult to estimate the rate of new HCV infections without following HCV-uninfected people over time and repeatedly testing them for HCV infection. Here, we present a novel, resource-efficient method to estimate the rate of new HCV infections in a population using data from a single timepoint.

Limited anti-HIV neutralizing antibody breadth and potency before and after HIV superinfection in Danish men who have sex with men.

BACKGROUND: The role of the anti-HIV neutralizing antibody response in protecting against HIV superinfection, and changes in neutralizing antibody potency and breadth after HIV superinfection have not been fully elucidated. This study examined the rate of HIV superinfection in men who have sex with men (MSM) also diagnosed with syphilis in Denmark, and the anti-HIV neutralizing antibody response in men who became superinfected. MATERIALS AND METHODS: MSM enrolled in the Danish HIV cohort who acquired syphilis were examined longitudinally for HIV superinfection using a validated next-generation sequencing assay. HIV superinfection cases were matched 3:1 to controls, and neutralizing antibody responses before (cases/controls) and after (cases) HIV superinfection were determined using a 20-pseudovirus panel. RESULTS: Four cases of HIV superinfection were identified from 95 MSM screened for a rate of HIV superinfection of 1.56/100 pys (95% CI = 0.43-4.01). Prior to HIV superinfection neutralizing antibody responses were low in breadth and potency, and did not differ between cases and controls (p = 1.0). In cases, neutralizing antibody responses increased modestly after HIV superinfection. CONCLUSIONS: These data support the theory that the natural neutralizing antibody response to HIV infection may not be the controlling factor in protecting against a subsequent HIV challenge.

Treatment as Prevention: Characterization of Partner Infections in the HIV Prevention Trials Network 052 Trial.

HIV Prevention Trials Network 052 demonstrated that antiretroviral therapy (ART) prevents HIV transmission in serodiscordant couples. HIV from index-partner pairs was analyzed to determine the genetic linkage status of partner infections. Forty-six infections were classified as linked, indicating that the index was the likely source of the partner's infection. Lack of viral suppression and higher index viral load were associated with linked infection. Eight linked infections were diagnosed after the index started ART: 4 near the time of ART initiation and 4 after ART failure. Linked infections were not observed when the index participant was stably suppressed on ART.

Asymmetry assessment using cone beam CT. A Class I and Class II patient comparison.

OBJECTIVE: To estimate possible differences in skeletal asymmetry between patients with skeletal Class I and skeletal Class II relationships. MATERIALS AND METHODS: Cone beam computed tomography (CBCT) images were examined from 70 consecutive patients who presented for orthodontic care and fit the inclusion criteria. Asymmetry was quantified using an asymmetry index developed by Katsumata et al. Anatomic landmarks were defined and reference planes were established to determine the asymmetry of the landmarks using a constructed coordinate plane system. Thirty randomly selected patients were reanalyzed to assess the reliability of the method. RESULTS: Statistical analysis did not find any significant relationship between asymmetry and A-P skeletal relationship for any of the landmarks. Asymmetry index scores were reproducible within a certain range of agreement for each landmark. CONCLUSIONS: Based on this study, the discrepant jaw growth resulting in a Class II skeletal pattern results in no more skeletal asymmetry than Class I skeletal patterns.

Improved lateral cephalometric superimposition using an automated image fitting technique.

OBJECTIVE: To test the feasibility of automated lateral cephalometric radiograph (LCR) superimposition using an image fitting algorithm. MATERIALS AND METHODS: Using radiopaque markers, we identified seven cephalometric landmarks on three dry skulls, took digital LCRs on each in several rotated positions, and used a custom software program (XRay3D) to automatically superimpose each rotated image on the initial image using an anterior cranial base reference. We measured superimposition error at each landmark and adjusted image brightness levels to simulate potential fitting error due to exposure variation. RESULTS: The greatest mean error for 24 image rotation trials of less than 10 degrees was less than 0.5 mm. Rotations of 10 degrees or more were not reliably superimposed. Errors of 0.2-1.6 mm occurred for +/-10% brightness but increased exponentially with further brightness alteration. CONCLUSION: Automated superimposition of LCRs, using this fitting technique, has great potential when rotation is less than 10 degrees and brightness variation is less than 10%.