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

Episomal Viral cDNAs Identify a Reservoir That Fuels Viral Rebound after Treatment Interruption and That Contributes to Treatment Failure

Viral reservoirs that persist in HIV-1 infected individuals on antiretroviral therapy (ART) are the major obstacle to viral eradication. The identification and definition of viral reservoirs in patients on ART is needed in order to understand viral persistence and achieve the goal of viral eradication. We examined whether analysis of episomal HIV-1 genomes provided the means to characterize virus that persists during ART and whether it could reveal the virus that contributes to treatment failure in patients on ART. For six individuals in which virus replication was highly suppressed for at least 20 months, proviral and episomal genomes present just prior to rebound were phylogenetically compared to RNA genomes of rebounding virus after therapy interruption. Episomal envelope sequences, but not proviral envelope sequences, were highly similar to sequences in rebounding virus. Since episomes are products of recent infections, the phylogenetic relationships support the conclusion that viral rebound originated from a cryptic viral reservoir. To evaluate whether the reservoir revealed by episomal sequence analysis was of clinical relevance, we examined whether episomal sequences define a viral population that contributes to virologic failure in individuals receiving the CCR5 antagonist, Vicriviroc. Episomal envelope sequences at or near baseline predicted treatment failure due to the presence of X4 or D/M (dual/mixed) viral variants. In patients that did not harbor X4 or D/M viruses, the basis for Vicriviroc treatment failure was indeterminate. Although these samples were obtained from viremic patients, the assay would be applicable to a large percentage of aviremic patients, based on previous studies. Summarily, the results support the use of episomal HIV-1 as an additional or alternative approach to traditional assays to characterize virus that is maintained during long-term, suppressive ART

Episomal Viral cDNAs Identify a Reservoir That Fuels Viral Rebound after Treatment Interruption and That Contributes to Treatment Failure

Viral reservoirs that persist in HIV-1 infected individuals on antiretroviral therapy (ART) are the major obstacle to viral eradication. The identification and definition of viral reservoirs in patients on ART is needed in order to understand viral persistence and achieve the goal of viral eradication. We examined whether analysis of episomal HIV-1 genomes provided the means to characterize virus that persists during ART and whether it could reveal the virus that contributes to treatment failure in patients on ART. For six individuals in which virus replication was highly suppressed for at least 20 months, proviral and episomal genomes present just prior to rebound were phylogenetically compared to RNA genomes of rebounding virus after therapy interruption. Episomal envelope sequences, but not proviral envelope sequences, were highly similar to sequences in rebounding virus. Since episomes are products of recent infections, the phylogenetic relationships support the conclusion that viral rebound originated from a cryptic viral reservoir. To evaluate whether the reservoir revealed by episomal sequence analysis was of clinical relevance, we examined whether episomal sequences define a viral population that contributes to virologic failure in individuals receiving the CCR5 antagonist, Vicriviroc. Episomal envelope sequences at or near baseline predicted treatment failure due to the presence of X4 or D/M (dual/mixed) viral variants. In patients that did not harbor X4 or D/M viruses, the basis for Vicriviroc treatment failure was indeterminate. Although these samples were obtained from viremic patients, the assay would be applicable to a large percentage of aviremic patients, based on previous studies. Summarily, the results support the use of episomal HIV-1 as an additional or alternative approach to traditional assays to characterize virus that is maintained during long-term, suppressive ART

Modeling Clinical Endpoints as a Function of Time of Switch to Second-line ART With Incomplete Data on Switching Times

Modeling clinical endpoints as a function of change in antiretroviral therapy (ART) attempts to answer one simple but very challenging question: was the change in ART beneficial or not? We conceive a similar scientific question of interest in the current manuscript except that we are interested in modeling the time of ART regimen change rather than a comparison of two or more ART regimens. The answer to this scientific riddle is unknown and has been difficult to address clinically. Naturally, ART regimen change is left to a participant and his or her provider and so the date of change depends on participant characteristics. There exists a vast literature on how to address potential confounding and those techniques are vital to the success of the method here. A more substantial challenge is devising a systematic modeling strategy to overcome the missing time of regimen change for those participants who do not switch to second-line ART within the study period even after failing the initial ART. In this paper, we adopt and apply a statistical method that was originally proposed for modeling infusion trial data, where infusion length may be informatively censored, and argue that the same strategy may be employed here. Our application of this method to therapeutic HIV/AIDS studies is new and interesting. Using data from the AIDS Clinical Trials Group (ACTG) Study A5095, we model immunological endpoints as a polynomial function of a participant’s switching time to second-line ART for 182 participants who already failed the initial ART. In our analysis, we find that participants who switch early have somewhat better sustained suppression of HIV-1 RNA after virological failure than those who switch later. However, we also found that participants who switched very late, possibly censored due to the end of the study, had good HIV-1 RNA suppression, on average. We believe our scientific conclusions contribute to the relevant HIV literature and hope that the basic modeling strategy outlined here would be useful to others contemplating similar analyses with partially missing treatment length data

The Ursinus Weekly, October 23, 1950

Bears trounce Garnet for first victory, 35-14 • Campus group will sponsor political rally • IRC plans events for near future • YM-YW commission to discuss president\u27s anti-red bill veto • Future teachers meet • Czech tells of red-occupied homeland to Bomberger Hall Forum audience • Group to organize unit of Red Cross • Senior class to sponsor masquerade Saturday • Clark, Deitch, Friedlin, and Maliken head freshman class • Congressman addresses Founders Day assembly • Curtain Club picks three members of Angel Street cast • Customs declared over by student councils • Phantasy reported in full rehearsal • Hundred and fifty girls attend annual junior-frosh breakfast • Editorial: Price of victory; Let\u27s send that TV set • Athletes keep new trainer busy • Scribe pens WSGA notes • Reporter ferrets facts about South, where life is chaotic but pleasant • MSGA discusses inter-dorm council, concession, and announcement limits • Delta Pi Sigma frat emerges as recognized social group • Bruins to clash with Seahawks at Staten Island • JV hockey squad whips Albright 11-0 • Booters tie alumni on Old Timers Day after mid-week 4-2 loss to Lafayette • Hockey team opens with 2-1 win over East Stroudsburg • Swarthmore bows 35-14 in first victory for Bears • Library to get additional tier of book racks • McPherson reigns as harvest queen at Varsity Club ball • Senior quartet makes debut on televisionhttps://digitalcommons.ursinus.edu/weekly/1549/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

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

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