Office of AIDS Research

The automatic identification of surface defects in industrial goods by visual inspection has increasingly supplanted human methods for identifying defects in steel strips, establishing itself as an essential component of surface defect detection in this context. A variety of steel items display several surface imperfections. Furthermore, these abnormalities exhibit considerable variation and similarity, presenting difficulty in their categorization. The existing models employed for defect identification exhibit low accuracy, presenting significant prospects for improvement. In this paper, we used light weight MobileNetV2 as a feature extractor and LGBM as a classifier for the classification of six distinct types of defects on steel surfaces. The proposed model achieved the highest accuracy of 97.5%. The experimental findings indicate that our suggested technique can proficiently categorize various steel surface flaws. A comparison with cuttingedge techniques demonstrates the advantages of the suggested strategy. Lastly, we applied explainable artificial intelligence using deep learning visualization techniques to highlight the area that is more used for the decision making by the model.

House object detection plays a pivotal role in enabling intelligent home automation, surveillance, and assistive technologies. The proposed model architecture integrates advanced modules—including convolutional layers, feature fusion blocks, and optimized detection heads—facilitating accurate multi-class localization. A robust data augmentation pipeline was employed using techniques like blur, grayscale conversion, and CLAHE to improve generalization. Experimental evaluation on the custom HomeObjects-3K dataset comprising 404 validation images with 3,466 object instances demonstrated strong detection performance. The model achieved an overall precision of 0.734, recall of 0.683, mAP@0.5 of 0.729.Notably photo frame (mAP@0.5: 0.876), sofa (0.878), and table (0.841) were detected with high accuracy.

Post-translational modification of proteins is a crucial biological reaction that regulates protein functions by altering molecular properties. The specific detection of such modifications in proteins has made significant contributions to molecular biology research and holds potential for future drug development applications. In HIV research, for example, tyrosine sulfation at the N-terminus of C-C chemokine receptor type 5 (CCR5) is considered to significantly enhance HIV infection efficiency. However, antibodies specific to sulfated CCR5 still need to be developed. In this study, we successfully generated an antibody that specifically recognized the sulfated N-terminal peptide of CCR5 through rabbit immunization and panning via phage display using a CCR5 N-terminal peptide containing sulfate modification. We used various physicochemical methods in combination with molecular dynamics simulation to screen for residues that could be involved in recognition of the sulfated peptide by this antibody. We also confirmed that this antibody recognized the sulfated full-length CCR5 on the cell surface, which suggested it should be useful as a research tool that could lead to the development of novel therapeutics. Although the antibody binding did not inhibit HIV infection, it could be also described as sulfation site-specific binding, beyond sulfation-specific binding.

IntroductionTenofovir‐based oral pre‐exposure prophylaxis is currently approved for HIV prevention; however, adherence in women has been low. A vaginal gel containing tenofovir (TFV) demonstrated partial protection to HIV but protection was not confirmed in additional studies. Vaginal rings offer user‐controlled long‐acting HIV prevention that could overcome adherence and protection challenges. TFV may also help prevent herpes simplex virus type 2 acquisition when delivered intravaginally. We evaluated the pharmacokinetics, safety, adherence and acceptability of a 90‐day TFV ring.MethodsBetween January and June 2019, Microbicide Trials Network (MTN)‐038 enrolled 49 HIV‐negative participants into a phase 1, randomized (2:1) trial comparing a 90‐day ring containing 1.4 grams (g) TFV to a placebo ring. TFV concentrations were quantified in plasma, cervicovaginal fluid (CVF), rectal fluid and cervical tissue, and TFV‐diphosphate (TFV‐DP) in cervical tissue. Used rings were analysed for residual TFV. Safety was assessed by adverse events (AEs); acceptability and adherence by self‐report.ResultsMean age was 29.5; 46 identified as cisgender‐female and three gender non‐conforming. There were no differences in the proportion of participants with grade ≥2 genitourinary AEs in the TFV versus placebo arms (p = 0.41); no grade ≥3 AEs were reported. Geometric mean TFV concentrations increased through day 34 in CVF/rectal fluid and day 59 in plasma, but declined across compartments by day 91. Geometric mean TFV‐DP tissue concentrations exceeded the 1000 fmol/mg target through day 56, but fell to 456 fmol/mg at day 91. Among 32 rings returned at the end of the study, 13 had no or low (<0.1 g) residual TFV. Residual TFV did not differ by socio‐demographics, sexual activity, Nugent Score or vaginal microbiota. Most participants reported being fully adherent to ring use: 85% and 81% in the TFV and placebo arms, respectively (p = 1.00). A majority of participants reported liking the ring (median 8 on a 10‐point Likert scale) and reported a high likelihood of using the ring in the future, if effective (median 9).ConclusionsThe 90‐day TFV ring was well‐tolerated, acceptable and exceeded target cervical tissue concentrations through day 56, but declined thereafter. Additional studies are needed to characterize the higher release from TFV rings in some participants and the optimal duration of use.

Abstract The success of antiretroviral therapy (ART) has led to an aging of the population of people with HIV (PWH). In the United States, over 50% of the 1.3 million PWH are currently over the age of 50. Studies have shown that PWH have advanced biological age as compared to the general population. Little is known about HIV and cancer characteristics in older PWH and the impact of these conditions on survival outcomes in this population. To evaluate this we conducted a retrospective review of PWH over the age of 60 years with cancer at the HIV and AIDS Malignancy Branch at the National Cancer Institute (NCI) from March 2001 to December 2021. We evaluated characteristics by age of intial cancer diagnosis (&amp;lt;60 years vs. &amp;gt;60 years) to determine the proportion of older PWH with a prior cancer diagnosis over their lifespan. We collected patient demographics, cancer and HIV characteristics, and other medical comorbidities. We calculated overall survival of patients from the age of 60 to last follow-up/death by Kaplan-Meier method and stratified by age at initial cancer diagnosis. We identified 32 patients (29 cisgender male, 3 cisgender female) who were seen in our clinic at the age of 60 years or older. 18 (56%) patients were diagnosed with cancer &amp;lt; 60 years and 14 (44%) were diagnosed &amp;gt; 60 years. 25 (78%) patients were non-Hispanic White and 7 (22%) were non-Hispanic Black. Kaposi sarcoma (20, 62%) was the most common cancer and cardiovascular disease (18, 56%) was the most common medical comorbidity in both age groups. Of the patients with cancer &amp;lt; 60 years, 12 (67%) were diagnosed with 1 cancer, and 6 (33%) had two or more cancer diagnoses. Of the patients diagnosed with cancer aged &amp;gt; 60 years, 8 (57%) were diagnosed with 1 cancer, and 6 (43%) were diagnosed with 2 or more cancers. Although patients diagnosed with cancer after 60 years presented with more comorbidities than patients diagnosed with cancer before 60, this was not significant (P= 0.72). HIV was well-controlled in all patients (median: 0 copies/mL, range: 0-216). The median CD4+ T cell count at age of cancer diagnosis was 420 cells/µl (range: 21-950) in those diagnosed &amp;lt;60 and 196 cells/µl (range: 20-682) diagnosed &amp;gt;60, which was not a significant difference (P= 0.54). All patients received cancer-directed therapy for their conditions. Of all patients 60 years and over who were evaluated, 12 patients (36%) died during follow-up, 10 of whom died of cancer. Of those who died during follow-up, 5 (26%) were diagnosed with cancer before 60 while 7 (50%) were diagnosed with cancer after age 60. Among all patients, the median overall survival was 6.8 years with a 5-year survival of 63%. There was no survival difference among those who were diagnosed with cancer before or after age 60 (P=0.10). As life expectancy improves among PWH, patients aged 60 years and over can experience one or more cancer diagnoses. Cancer care in this population requires a multidisciplinary approach that accounts for concurrent medical comorbidities that can impact the treatment course and survival outcomes. Citation Format: Tishiya Carey, Ralph Mangusan, Anaida Widell, Irene Ekwede, Kathyrn Lurain, Ramya Ramaswami. Survival outcomes in older people living with HIV and cancer [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B008.

Over the past two decades there have been major advances in the development of interventions promoting mental health and well-being in low- and middle-income countries (LMIC), including delivery of care by non-specialist providers, incorporation of mobile technologies and development of multilevel community-based interventions. Growing inequities in mental health have led to calls to adopt similar strategies in high-income countries (HIC), learning from LMIC. To overcome shared challenges, it is crucial for projects implementing these strategies in different global settings to learn from one another. Our objective was to examine cases in which mental health and well-being interventions originating in or conceived for LMIC were implemented in the USA. The cases included delivery of psychological interventions by non-specialists, HIV-related stigma reduction programmes, substance use mitigation strategies and interventions to promote parenting skills and family functioning. We summarise commonly used strategies, barriers, benefits and lessons learnt for the transfer of these innovative practices among LMIC and HIC. Common strategies included intervention delivery by non-specialists and use of digital modalities to facilitate training and increase reach. Common barriers included lack of reimbursement mechanisms for care delivered by non-specialists and resistance from professional societies. Despite US investigators’ involvement in most of the original research in LMIC, only a few cases directly involved LMIC researchers in US implementation. In order to achieve greater equity in global mental health and well-being, more efforts and targeted funding are needed to develop best practices for global health reciprocal innovation and iterative learning in HIC and LMIC.

There is an urgent need to increase diversity among scientific investigators in the HIV research field to be more reflective of communities highly affected by the HIV epidemic. Thus, it is critical to promote the inclusion and advancement of early-stage scholars from racial and ethnic groups underrepresented in HIV science and medicine. To widen the HIV research career pathway for early-stage scholars from underrepresented minority groups, the National Institutes of Health supported the development of the Centers for AIDS Research (CFAR) Diversity, Equity, and Inclusion Pathway Initiative (CDEIPI). This program was created through partnerships between CFARs and Historically Black Colleges and Universities and other Minority Serving Institutions throughout the United States. Seventeen CFARs and more than 20 Historically Black Colleges and Universities and Minority Serving Institutions have participated in this initiative to date. Programs were designed for the high school (8), undergraduate (13), post baccalaureate (2), graduate (12), and postdoctoral (4) levels. Various pedagogical approaches were used including didactic seminar series, intensive multiday workshops, summer residential programs, and mentored research internship opportunities. During the first 18 months of the initiative, 257 student scholars participated in CDEIPI programs including 150 high school, 73 undergraduate, 3 post baccalaureate, 27 graduate, and 4 postdoctoral students. Numerous student scholars from a wide range of educational levels, geographic backgrounds, and racial and ethnic minority groups have engaged in CDEIPI programs. Timely and comprehensive program evaluation data will be critical to support a long-term commitment to this unique training initiative.

The aim of this study was to evaluate baseline differences by HIV status and the impact of pomalidomide on lymphocyte counts and T-cell subsets in patients with Kaposi sarcoma. We prospectively evaluated CD4 + and CD8 + T-cell phenotypes in 19 participants with Kaposi sarcoma enrolled on a phase 1/2 study of pomalidomide (NCT01495598), seven without HIV and 12 with HIV on antiretroviral therapy. Trial participants received pomalidomide 5 mg orally for 21 days of 28-day cycles for up to 1 year. Flow cytometry was performed on peripheral blood mononuclear cells at baseline, after three cycles, and at end-of-treatment. Lymphocyte count and T-cell subset comparisons were evaluated by Wilcoxon signed-rank and Mann--Whitney tests. At baseline, HIV + participants had lower CD4 + cell counts (median 416 vs. 742 CD4 + T cells/μl, P = 0.006), and a decreased proportion of CD57 + (senescent) CD8 + T cells ( P = 0.007) compared with HIV - participants. After three cycles, pomalidomide led to an increased proportion of CD45RO + CD27 + (central memory) CD4 + ( P = 0.002) and CD8 + ( P = 0.002) T cells, a decrease in CD45RO - CD27 - (effector) CD4 + cells ( P = 0.0002), and expansion of CD38 + /HLADR + (activated) CD4 + ( P = 0.002) and CD8 + ( P ≤ 0.0001) T cells. Increased numbers of activated CD8 + T cells persisted at end-of-treatment ( P = 0.002). After three cycles and at end-of-treatment, there was reduction in the proportion of CD57 + (senescent) CD4 + ( P = 0.001, 0.0006), and CD8 + ( P = < 0.0001, 0.0004) T cells. Administration of pomalidomide decreased T-cell senescence and increased T-cell activation in patients with Kaposi sarcoma, suggesting pomalidomide activity in Kaposi sarcoma stems in part from its immunomodulatory effects.