The International Workshop on HIV Persistence during Therapy provides a forum in which HIV/AIDS researchers gather to share the latest research findings related to viral reservoirs and cure. The Tenth Workshop, which was attended by over 400 delegates, extended over 4 days and comprised eight sessions covering topics from the basic science of viral persistence to therapeutic approaches to HIV cure. Furthermore, satellite sessions on the first day of the Conference featuring cure research endeavours being pursued by the Bill and Melinda Gates Foundation as well as those being coordinated under the National Institutes of Health Martin Delaney Collaboratory program, provided important updates on research advances being made in these initiatives. As with previous conferences, the International Workshop on HIV Persistence during Therapy is primarily abstract-driven with only one invited talk for each of the sessions. This format, therefore, increases the number of presentations from early-stage investigators. Furthermore, presentations by Community representatives illustrated approaches to creating cure research literacy with effective messaging for the Community. The following article offers a synopsis of the meeting sessions. Due to space constraints, some presentations may have only been briefly discussed. Nevertheless, the Workshop abstracts can be found online (https://www/sciencedirect.com/journal/journal-of-virus-eradication/vol/8/suppl/S).

In this comparative effectiveness study, we compare the survival outcomes for hospitalized COVID-19 patients treated with remdesivir (RDV) upon admission vs. those not treated with RDV. We used the Premier Healthcare Database to examine patients hospitalized between Aug-Nov 2020 and treated with RDV within 2 days of hospitalization vs. those who did not receive RDV during their hospitalization. Preferential within-hospital propensity score matching with replacement was used. Patients were matched on baseline oxygen requirement and 2-month admission period and were excluded if discharged within 3 days of RDV initiation (to exclude anticipated discharges/transfers within 72 hrs consistent with ACTT-1 study). Cox Proportional Hazards models were used to examine 14- and 28-day mortality overall and for patients on no supplemental oxygen (NSO), low-flow oxygen (LFO), high-flow oxygen/non-invasive ventilation (HFO/NIV) and invasive mechanical ventilation/ECMO (IMV/ECMO) separately. RDV patients (n=28,855) were matched to unique non-RDV patients (n=16,687). The two groups were balanced. At baseline, 28% required NSO, 48% LFO, 20% HFO/NIV and 4% IMV/ECMO. Mortality in RDV patients was 10.6% and 15.4% on days 14 and 28, respectively. For non-RDV patients, mortality was 15.4% and 19.1% on days 14 and 28, respectively. After adjusting for baseline and clinical covariates, RDV patients had significantly lower risk of mortality at 14-days (HR[95% CI]: 0.76[0.70−0.83]) and 28-days (0.89[0.82−0.96]). This mortality benefit was also seen for NSO, LFO and IMV/ECMO patients at 14-days (NSO: 0.69[0.57−0.83], LFO: 0.68[0.80−0.77], IMV/ECMO: 0.70[0.58−0.84]) and 28-days (NSO: 0.80[0.68−0.94], LFO: 0.77[0.68−0.86], IMV/ECMO: 0.81[0.69−0.94]). Additionally, HFO/NIV RDV patients had a significantly lower risk of mortality at 14-days (0.81[0.70−0.93]); but not at 28-days. In this observational study, treatment with RDV was associated with statistically significant reduction in mortality among hospitalized COVID-19 patients. These results complement the findings from the ACTT-1 and contribute to the growing body of evidence on the survival benefits of RDV.

Individual sperm cells are resolved from a syncytium during late step of spermiogenesis known as individualization, which is accomplished by an Individualization Complex (IC) composed of 64 investment cones. mulet encodes Tubulin-binding cofactor E-like (TBCEL), suggesting a role for microtubule dynamics in individualization. Indeed, a population of ∼100 cytoplasmic microtubules fails to disappear in mulet mutant testes during spermatogenesis. This persistence, detected using epi-fluorescence and electron microscopy, suggests that removal of these microtubules by TBCEL is a prerequisite for individualization. Immunofluorescence reveals TBCEL expression in elongated spermatid cysts. In addition, testes from mulet mutant males were rescued to wild-type using tubulin-Gal4 to drive TBCEL expression, indicating that the mutant phenotype is caused by the lack of TBCEL. Finally, RNAi driven by bam-GAL4 successfully phenocopied mulet, confirming that mulet is required in the germline for individualization. We propose a model in which the cytoplasmic microtubules serve as alternate tracks for investment cones in mulet mutant testes.

AIDS Clinical Trials Group study A5308 found reduced T-cell activation and exhaustion in HIV controllers initiating antiretroviral therapy (ART). We further assessed HIV-specific T-cell responses and post-ART viral loads. Pre-ART, the 31% of participants with persistently undetectable viremia had more robust HIV-specific T-cell responses. On ART, significant decreases were observed in a broad range of T-cell responses. Eight controllers in A5308 and the SCOPE cohort showed no viremia above the level of quantification in the first 12 weeks after ART discontinuation. ART significantly reduced HIV-specific T-cell responses in HIV controllers but did not adversely affect controller status after ART discontinuation.

BACKGROUND Despite low plasma HIV RNA, HIV controllers have evidence of viral replication and elevated inflammation. We assessed the effect of antiretroviral therapy (ART) on HIV suppression, viral reservoir, immune activation, and quality of life in this population. METHODS A5308 was a prospective, open-label study of rilpivirine/emtricitabine/tenofovir disoproxil fumarate in ART-naïve HIV controllers (N=35), defined as having HIV RNA <500 copies/mL for ≥12 months. The primary outcome measured change in %CD38+HLA-DR+ CD8+ T cells. Residual plasma viremia was measured by the integrase single-copy assay (iSCA) and reservoir size by total HIV DNA in CD4+ T cells. Quality of life (QoL) was measured by the EQ-5D questionnaire. Outcomes were evaluated by repeated measures GEE models. RESULTS Before ART, HIV controllers with undetectable residual viremia <0.6 HIV-1 RNA copies/mL had higher CD4+ counts and lower levels of T cell activation than those with detectable residual viremia. ART use was effective in further increasing the proportion of individuals with undetectable residual viremia (pre-ART vs. after 24-48 weeks of ART: 19% vs. 94%, P<0.001). Significant declines were observed in the %CD38+HLA-DR+CD8+ T cells at 24-48 (-4.0%, P=0.001) and 72-96 (-7.2%, P<0.001) weeks after ART initiation. ART use resulted in decreases of several cellular markers of immune exhaustion and in a modest but significant improvement in self-reported QoL. There were no significant changes in CD4+ counts or HIV DNA. CONCLUSIONS ART in HIV controllers reduces T cell activation and improves markers of immune exhaustion. These results support the possible clinical benefits of ART in this population.

Catherine Godfrey,1 Michael C. Thigpen,1 Keith W. Crawford,1 Patrick Jean-Phillippe,1 Deenan Pillay,2 Deborah Persaud,3 Daniel R. Kuritzkes,4 Mark Wainberg,5,† Elliot Raizes,6 and Joseph Fitzgibbon1 1National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland; 2University College London, United Kingdom; 3Johns Hopkins University, Baltimore, Maryland; 4Brigham and Women’s Hospital, Boston, Massachusetts; 5McGill University, Montreal, Canada; and 6Centers for Disease Control and Prevention, Atlanta, Georgia

Einleitung: Die Therapie der HCV Infektion besteht aus verschiedenen Kombinationen direkt antiviraler Medikamente (DAAs)± pegyliertes Interferon-alpha und/oder Ribavirin (R). Der HCV Genotyp (GT) ist der wichtigste Faktor für die Auswahl der optimalen Therapie. Der rekombinante GT2k/1b wird bei routinemäßigen Genotypisierungen nicht erkannt und als GT2 bestimmt, wenn nicht die 5' und 3' Regionen des HCV Genoms analysiert werden. Dies kann zur medikamentösen Unterversorgung führen, da sich die Behandlung von GT2 und GT1 Patienten unterscheidet.

Antiretroviral therapies have proved life‐saving in HIV infection, dramatically reducing morbidity and mortality. With longer survival, morbidities and mortalities in HIV infection are increasingly similar to the morbidities and mortalities associated with ageing. In treated HIV infection, the risk of these morbidities and mortalities is linked to immune activation, inflammation and coagulation indices. And in persons with treated HIV infection, failure to restore circulating CD4 T cell numbers is associated with a greater risk of morbidities and mortalities as well as to heightened levels of inflammation and coagulation. The drivers of immune activation, inflammation and coagulation in treated HIV infection are incompletely defined and could be related to sustained low levels of viral replication in tissues, to translocation of microbial products across a damaged gut mucosa, to replication of co‐pathogens such as cytomegalovirus, to increased levels of inflammatory lipids, or to homeostatic responses to lymphocytopenia that may drive expansion of CD8 T cell numbers. We present here models that link inflammation and coagulation to morbid outcomes as well as to the pathogenesis of CD4 T cell restoration failure and CD8 T cell expansion.

Although current antiretroviral therapy (ART) for human immunodeficiency virus (HIV) successfully controls infection and reduces mortality, curing infection is an important goal. This article reviews the cases of patients who might be appropriate candidates for an attempt at curing HIV infection, elite controllers, the role of HIV reservoirs, and the development of therapeutic vaccines to cure HIV infection.