The Ursinus Weekly, October 2, 1950

B-listers roll up big 63-40 victory over Dean\u27s team • Enrollment drops to 805; Freshmen number 197 • Pre-medders plan to present talks at their meetings • Co-editors of 1950 yearbook announce appointment of 13 department leaders • Japanese educator visits F. I. Sheeder and College • Y members clean recreation center • Curfew notice • Editor announces positions available on Lantern staff • Improper parkers served notice • Y schedules events for near future; Rally Wednesday • Thespians to hold reception Tuesday at Super House • Omwake leaves Ursinus to accept Virginia post • Robert Rosenberger confined to St. Joseph\u27s Hospital, Reading • Veterans notices • New course offered • Editorial: Destiny; Welcome • Councils clarify freshman customs • Frosh girl hails from Iraq • Scribe pens WSGA notes • Y reception committee expands activity; Wins plaudits for its freshmen program • Ursinus grad gains Bowling Green post • Public causes problems for seeing eye dogs • In memoriam • IRC plans Lehigh trip to hear talk on China • Whistler and cohorts boost morale as fighting spirit invades campus • Studio Cottage singers • Gurzynski first alumnus to guide Bears since 1931 • Booters start practice under genial Dr. Baker • Drexel whips Bears 26-0 to open \u2750 grid season • Gerry Roughton escapes Korean crisis; Evacuates Seoul during red onslaught • ETS announces law admission and grad record exam dates • Pancoast constructs new home; Summer work aids completionhttps://digitalcommons.ursinus.edu/weekly/1546/thumbnail.jp

Evaluating the Effect of Early Versus Late ARV Regimen Change if Failure on an Initial Regimen: Results From the AIDS Clinical Trials Group Study A5095

The current goal of initial antiretroviral (ARV) therapy is suppression of plasma human immunodeficiency virus (HIV)-1 RNA levels to below 200 copies per milliliter. A proportion of HIV-infected patients who initiate antiretroviral therapy in clinical practice or antiretroviral clinical trials either fail to suppress HIV-1 RNA or have HIV-1 RNA levels rebound on therapy. Frequently, these patients have sustained CD4 cell counts responses and limited or no clinical symptoms and, therefore, have potentially limited indications for altering therapy which they may be tolerating well despite increased viral replication. On the other hand, increased viral replication on therapy leads to selection of resistance mutations to the antiretroviral agents comprising their therapy and potentially cross-resistance to other agents in the same class decreasing the likelihood of response to subsequent antiretroviral therapy. The optimal time to switch antiretroviral therapy to ensure sustained virologic suppression and prevent clinical events in patients who have rebound in their HIV-1 RNA, yet are stable, is not known. Randomized clinical trials to compare early versus delayed switching have been difficult to design and more difficult to enroll. In some clinical trials, such as the AIDS Clinical Trials Group (ACTG) Study A5095, patients randomized to initial antiretroviral treatment combinations, who fail to suppress HIV-1 RNA or have a rebound of HIV-1 RNA on therapy are allowed to switch from the initial ARV regimen to a new regimen, based on clinician and patient decisions. We delineate a statistical framework to estimate the effect of early versus late regimen change using data from ACTG A5095 in the context of two-stage designs

The Ursinus Weekly, December 4, 1950

Gillespie to play at Friday night senior formal • Men students cast 107-71 vote against dorm amendment • Music organizations to present Messiah in Bomberger chapel Thursday night • Y Commissions to meet; PAC plans Xmas party • Response to WSSF is disappointing; Receipts total $350 • Critic hails Angel Street as vehicle for superb thespian dramatic acting • Hungarian to address Tuesday night Forum • Twelve to become Rosicrucians • Yule traditions dominate ensuing campus activities • Bloodmobile to be at Trinity church Thursday morning • 26 are accepted by local chapter of Pi Gamma Mu • Cafe Pigalle to return to gym Saturday night • Mary MacPherson chosen May Queen; Marge Paynter named pageant manager • Editorial: Dynamic force • WSGA notes • Delta Pi Sigma welcomes ten off-campus men • English Club admits members • Revived rec center attracts many • 45 future teachers approach termination of tribulation • IRC hears attorney speak on problems of western nations • Ruby schedules photos, pushes subscriptions • Pigskin parade • Bears top textile 64-50 in court season inaugural • Six close careers on soccer squad • Derr deadlocks Albright 6-6 • Four senior girls play hockey finale • Grid player scans all-state selections • Ursinus grid aggregation suffers loss of twelve graduating upper classmen • Penn triumphs 3-1 over Ursinus girls • Reid Watson became football manager when injury benched former grid star • Messiah reputation stems from mastery of simple techniques • Eight teams compete in debate tournament • Chess team loses • Kershner does dialect in fourth lit readinghttps://digitalcommons.ursinus.edu/weekly/1554/thumbnail.jp

The Ursinus Weekly, January 8, 1951

Group attends NSA meeting during holiday • French Club conducts meeting and lists plans • Final examinations to continue January 18-26; Schedule posted • Chess Club to play • Rice to give talk on Atlantic Union • Sophomore class to sponsor square dance Friday night • President McClure issues statement on present draft situation at Ursinus • College offers new two-term Summer school • Graduate featured in magazine story • Curtain Club announces next group production • Students participate in television show • Forty attend Philly luncheon of Ursinus Women\u27s Club • New Rosicrucians feted • Miller appears on Quaker City TV University • Ursinus grad to hold state executive office • Opinions on Korea: Ursinus representatives speak their minds • Double-duty secretary gowns directors for processions, manages switchboard • Downpour predicted; Waterproof notes, dry textbooks, precautions prescribed • Prognostication shows alteration of future strife in college life • Bears upset F&M 73-55 in pre-holiday thriller • Grapplers win opener over Muhlenberg, 23-9 • Grizzlies absorb second cage loss to Pharmacy five • Bruins top Drexel 80-74 in initial league contest • Trials highlight MSGA pre-vacation meetinghttps://digitalcommons.ursinus.edu/weekly/1556/thumbnail.jp

Relationship between latent and rebound viruses in a clinical trial of anti-HIV-1 antibody 3BNC117.

A clinical trial was performed to evaluate 3BNC117, a potent anti-HIV-1 antibody, in infected individuals during suppressive antiretroviral therapy and subsequent analytical treatment interruption (ATI). The circulating reservoir was evaluated by quantitative and qualitative viral outgrowth assay (Q2VOA) at entry and after 6 mo. There were no significant quantitative changes in the size of the reservoir before ATI, and the composition of circulating reservoir clones varied in a manner that did not correlate with 3BNC117 sensitivity. 3BNC117 binding site amino acid variants found in rebound viruses preexisted in the latent reservoir. However, only 3 of 217 rebound viruses were identical to 868 latent viruses isolated by Q2VOA and near full-length sequencing. Instead, 63% of the rebound viruses appeared to be recombinants, even in individuals with 3BNC117-resistant reservoir viruses. In conclusion, viruses emerging during ATI in individuals treated with 3BNC117 are not the dominant species found in the circulating latent reservoir, but frequently appear to represent recombinants of latent viruses

Mass spectrometry imaging of hair identifies daily maraviroc adherence in HPTN 069/ACTG A5305

Objective measures of adherence for antiretrovirals used as pre-exposure prophylaxis (PrEP) are critical for improving preventative efficacy in both clinical trials and real-world application. Current objective adherence measures either reflect only recent behavior (eg days for plasma or urine) or cumulative behavior (eg months for dried blood spots). Here, we measured the accumulation of the antiretroviral drug maraviroc (MVC) in hair strands by infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) mass spectrometry imaging (MSI) to evaluate adherence behavior longitudinally at high temporal resolution. An MSI threshold for classifying daily adherence was established using clinical samples from healthy volunteers following directly observed dosing of 1 to 7 doses MVC/week. We then used the benchmarked MSI assay to classify adherence to MVC-based PrEP regimens in hair samples collected throughout the 48-week HPTN069/ACTGA5305 study. We found that only ~32% of investigated hair samples collected during the study’s active dosing period showed consistent daily PrEP adherence throughout a retrospective period of 30 days, and also found that profiles of daily individual adherence from MSI hair analysis could identify when patients were and were not taking study drug. The assessment of adherence from MSI hair strand analysis was 62% lower than adherence classified using paired plasma samples, the latter of which may be influenced by white-coat adherence. These findings demonstrate the ability of MSI hair analysis to examine daily variability of adherence behavior over a longer-term measurement and offer the potential for longitudinal comparison with risk behavior to target patient-specific adherence interventions and improve outcomes

The Ursinus Weekly, May 7, 1951

Bill LeKernec to edit next year\u27s Lantern • Sororities elect new officers, plan events • Varsity banquet tonight • W. A. A. holds election • Y members plan 1951-52 activities at camp retreat • Campus ready for May Day; Pageant, play to be big events • Professors tackle broad questions in first panel • YM-YW name cabinet, heads of commission • Graduation announcements available to seniors • Students cast primary votes for officers • Election of Curtain Club officers listed • Chi Alpha to elect • Editorials: System a success • Making of foreign policy • Letters to the editor • Three officials embroiled • Ursinus mentioned in Gramercy Ghost • May Day histories reveal variety of festivities • Weekly scribe sheds light on life of famous Ursinus College athlete • Local lassies win 4-1 over Rosemont • Interfraternity track meet to begin this Wednesday • Temple women defeat local tennis squad on May 2 • Cindermen win as Eshbach, Scheirer and Loomis are double winners • Bears capitalize on four hits to beat Garnet • Moravian, Elizabethtown suffer as netmen extend streak to four • Ursinus enters three in intercollege tennis • Bearettes shut-out Albright squad • Lincoln nine halts rally to defeat Grizzlies, 6 to 3 • Curtis clinches first place slots in both leagues • Women\u27s softball team defeats Drexel, Temple • Forum speaker tells of Turkey\u27s position • Dr. Rice invited to Washington for Atlantic Union Conference • Ann Knaur elected President of French Club • Rec center party planned • Women day students hold senior dinner • Supper tickets on sale • Chess Club ends successful season • Shaw named prexyhttps://digitalcommons.ursinus.edu/weekly/1568/thumbnail.jp

Quantitative Deep Sequencing Reveals Dynamic HIV-1 Escape and Large Population Shifts during CCR5 Antagonist Therapy In Vivo

High-throughput sequencing platforms provide an approach for detecting rare HIV-1 variants and documenting more fully quasispecies diversity. We applied this technology to the V3 loop-coding region of env in samples collected from 4 chronically HIV-infected subjects in whom CCR5 antagonist (vicriviroc [VVC]) therapy failed. Between 25,000–140,000 amplified sequences were obtained per sample. Profound baseline V3 loop sequence heterogeneity existed; predicted CXCR4-using populations were identified in a largely CCR5-using population. The V3 loop forms associated with subsequent virologic failure, either through CXCR4 use or the emergence of high-level VVC resistance, were present as minor variants at 0.8–2.8% of baseline samples. Extreme, rapid shifts in population frequencies toward these forms occurred, and deep sequencing provided a detailed view of the rapid evolutionary impact of VVC selection. Greater V3 diversity was observed post-selection. This previously unreported degree of V3 loop sequence diversity has implications for viral pathogenesis, vaccine design, and the optimal use of HIV-1 CCR5 antagonists

Genotypic Susceptibility Scores and HIV Type 1 RNA Responses in Treatment-Experienced Subjects with HIV Type 1 Infection

This study compared the role of genotypic susceptibility scores (GSS) as a predictor of virologic response in a group (n = 234) of HIV-infected, protease inhibitor (PI)-experienced subjects. Two scoring methods [discrete genotypic susceptibility score (dGSS) and continuous genotypic susceptibility score (cGSS)] were developed. Each drug in the subject's regimen was given a binary susceptibility score using Stanford inferred drug resistance scores to calculate the dGSS. In contrast to the dGSS, the cGSS model was designed to reflect partial susceptibility to a drug. Both GSS were independent predictors of week 16 virologic response. We also compared the GSS to a phenotypic susceptibility score (PSS) model on a subset of subjects that had both GSS and PSS performed, and found that both models were predictive of virologic response. Genotypic analyses at enrollment showed that subjects who were virologic nonresponders at week 16 revealed enrichment of several mutated codons associated with nucleoside reverse transcriptase inhibitors (NRTI) (codons 67, 69, 70, 118, 215, and 219) or PI resistance (codons 10, 24, 71, 73, and 88) compared to subjects who were virologic responders. Regression analyses revealed that protease mutations at codons 24 and 90 were most predictive of poor virologic response, whereas mutations at 82 were associated with enhanced virologic response. Certain NNRTI-associated mutations, such as K103N, were rapidly selected in the absence of NRTIs. These data indicate that GSS may be a useful tool in selecting drug regimens in HIV-1-infected subjects to maximize virologic response and improve treatment outcomes

Proteinuria, CrCl, and Immune Activation in Antiretroviral-Naïve HIV-Infected Subjects

Because both renal disease and immune activation predict progression to AIDS, we evaluated the relationships between dipstick proteinuria ≥1+ [7% of 1012 subjects], CrCl <90mL/min [18% of 1071 subjects], and percentages of peripheral activated CD8 cells (CD8+CD38+HLA-DR+) in antiretroviral-naïve, HIV-infected subjects enrolled into AIDS Clinical Trials Group studies 384 and A5095. Proteinuria, but not CrCl, was associated with higher percentages of CD8+CD38+HLA-DR+ cells [55% vs. 50%; P=0.01], with even more pronounced differences in men and among Blacks and Hispanics. Proteinuria may be a surrogate measure of greater immune activation in HIV-infected patients initiating antiretroviral therapy