AIDS research and human retroviruses最新文献

{"title":"Early Implementation and Outcomes Among People with HIV Who Accessed Long-Acting Injectable Cabotegravir/Rilpivirine at Two Ryan White Clinics in the U.S. South.","authors":"Grace C Haser, Laurence Balter, Stephen Gurley, Marsha Thomas, Thomas Murphy, Jeri Sumitani, Eric Paul Leue, Angela Hollman, Maima Karneh, Leah Wray, Melissa Washington, Della Corbin-Johnson, Alton Condra, Larisa Niles-Carnes, Bradley L Smith, Wendy S Armstrong, Ameeta S Kalokhe, Jonathan A Colasanti, Lauren F Collins","doi":"10.1089/AID.2024.0007","DOIUrl":"10.1089/AID.2024.0007","url":null,"abstract":"<p><p>The use of long-acting injectable cabotegravir/rilpivirine (LAI-CAB/RPV) as maintenance therapy for persons with HIV (PWH), which may improve treatment access and outcomes, though real-world data on uptake are limited, was studied at two Ryan White clinics in Atlanta, Georgia. Among PWH referred from 4/1/2021 to 9/15/2022 to switch to LAI-CAB/RPV, characteristics were ascertained at time of referral; and disposition (initiated; ineligible; uninterested; pending) was recorded as of 9/15/2022. Among patients initiated on CAB/RPV, we assessed the drug procurement process and clinical outcomes through 6/1/2023. Among 149 PWH referred, 74/149 (50%) initiated CAB/RPV as of 9/15/2022, of whom, characteristics were median age 47 (Q1-Q3 36-55) years, 16% cisgender female, 72% Black race, median HIV duration 15 (Q1-Q3 9-19) years, and 64% had commercial health insurance. Of the 75 PWH not initiated, 35 were ineligible owing to a clinical concern (<i>n</i> = 16) or insurance issue (<i>n</i> = 19); 15 patients changed their mind about switching; and 25 were pending eligibility review or therapy initiation. Median time from CAB/RPV prescription to initiation was 46 (Q1-Q3 29-78) days. Of 731 total injections administered (median 11 injections/patient), 95% were given within 7 days of the target treatment date. Nearly all patients were virally suppressed upon referral and remained suppressed through follow-up. At two clinics in the U.S. South, half of the patients referred for LAI-CAB/RPV successfully accessed therapy nearly 2 years after U.S. drug approval. We identified barriers to uptake at the patient and structural levels, highlighting key areas to invest resource and personnel support to sustain and scale long-acting antiretroviral therapy programming.</p>","PeriodicalId":7544,"journal":{"name":"AIDS research and human retroviruses","volume":" ","pages":"690-700"},"PeriodicalIF":1.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11807906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141496840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of a Novel HIV-1 Circulating Recombinant Form (CRF150_Cpx) Among Men Who Have Sex with Men in China.","authors":"Min Chen, Huichao Chen, Jie Dai, Lijuan Dong, Yanling Ma, Manhong Jia","doi":"10.1089/AID.2024.0061","DOIUrl":"10.1089/AID.2024.0061","url":null,"abstract":"<p><p>Recent studies have reported increasing complexity in human immunodeficiency virus 1 (HIV-1) genotypes among men who have sex with men (MSM) in China. In an HIV-1 molecular epidemiological study conducted among MSM in Yunnan Province, China, we discovered that four samples could potentially represent a circulating recombinant form (CRF). In this study, we conducted further analysis on their nearly full-length genome (NFLG) sequences. The NFLG sequences formed a distinct monophyletic clade in the phylogenetic tree. Recombination analysis indicated that the four sequences were constructed upon the backbone of CRF149_01B, with the insertion of three CRF07_BC fragments. Consequently, they were designated as CRF150_cpx. Evolutionary analyses suggested that CRF150_cpx emerged between approximately 2014 and 2015. The identification of new CRFs not only deepens our understanding of HIV recombination but also aids in comprehending the prevalence and transmission history of HIV among specific populations.</p>","PeriodicalId":7544,"journal":{"name":"AIDS research and human retroviruses","volume":" ","pages":"728-732"},"PeriodicalIF":1.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141900622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transmitted Antiretroviral Drug Resistance to Integrase Strand Transfer Inhibitors Class in São Paulo Metropolitan Area, Brazil.","authors":"Elaine Monteiro Matsuda, Jaqueline Helena da Silva Santos, Cintia Mayumi Ahagon, Giselle Ibete Silva López-Lopes, Luís Fernando de Macedo Brígido","doi":"10.1089/AID.2023.0127","DOIUrl":"10.1089/AID.2023.0127","url":null,"abstract":"<p><p>A newer integrase strand transfer inhibitor (INSTI) cabotegravir was recently approved for both therapy and prophylaxis and can play an essential role in the fight against AIDS. It shares similar resistance profile to dolutegravir, the cornerstone of Brazilian antiretroviral (ARV) treatment, with about 600 thousand people living with HIV in Brazil currently on regimens that contain this INSTI. Health services in the São Paulo metropolitan area are responsible for a large proportion of ARV dispensation in the country. Estimating transmitted drug resistance mutation (TDRM) in the area before cabotegravir introduction may provide a useful baseline information. Partial HIV-1 <i>pol</i> gene was sequenced (Sanger) from 192 newly diagnosed individuals from São Paulo and nearby cities (2020 to March 2023) at integrase, with 85 also at protease/reverse transcriptase regions. Retrotranscribed plasma RNA, amplified with nested PCR, was edited (Recall or Sequencher) and analyzed at Rega and Stanford db. Surveillance drug resistance mutations (SDRM) to INSTI class was detected in three cases (1.6%; 95% CI: 0.5%-5%), two E138K and one R263K, with 7.8% (95% CI: 5%-13%) with resistance mutations (major or accessory). SDRM for nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, and PI classes were identified in 7 (8.2% CI: 95% 4%-16%) cases. Subtype B predominated (69%), followed by subtype C (16%), now the second most prevalent infection in this area. Among 131 patients treated for over 6 months, 92% were virally suppressed below 200 copies/mL, with low TCD4 counts independently associated to failure. SDRM to INSTI class is rare in the area. Intermediate rates of transmitted resistance to other ARV classes are comparable to previous estimates. Viral suppression rates may depend on TCD4 counts, another negative impact of late diagnosis in care that deserves more attention.</p>","PeriodicalId":7544,"journal":{"name":"AIDS research and human retroviruses","volume":" ","pages":"713-717"},"PeriodicalIF":1.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Integrated DAIDS Laboratory Oversight Framework: Application of the DAIDS GCLP Guidelines.","authors":"Naana Cleland, Nina Kunwar, Usha Sharma, Jamal Dejli, Milton Maciel, Daniella Livnat, Judith Miller, Keith Crawford, Fatima Jones, M Patricia D'Souza","doi":"10.1089/AID.2024.0041","DOIUrl":"10.1089/AID.2024.0041","url":null,"abstract":"<p><p>The Division of AIDS (DAIDS) Good Clinical Laboratory Practice (GCLP) Guidelines establish a framework to guide the oversight of laboratories supporting DAIDS-sponsored clinical research or trials. Compliance with these guidelines promotes data reliability, consistency, and validity, and the safety of the clinical research or trial participants and laboratory staff, as well as ensures adherence to regulatory requirements. This article describes the application of the DAIDS GCLP Guidelines, the DAIDS Integrated Laboratory Oversight Framework, and the coordinated efforts of the collaborative oversight team of laboratory experts to support and monitor the performance of over 175 participating laboratories worldwide. Data from two self-administered online surveys conducted in 2017 and 2023 assessed the laboratory staff's experience implementing the GCLP Guidelines. The results of the 2017 survey were instrumental in informing changes to GCLP audit activities and promoting harmonization in the approach to laboratory oversight. A key finding from the 2023 survey results is the preference for hybrid GCLP training, encompassing face-to-face and online modules. Overall, both surveys acknowledged satisfaction with applying and implementing GCLP Guidelines. The need to effectively disseminate information about DAIDS laboratory oversight requirements to support the improved implementation of GCLP Guidelines was notable from both survey results. The collaborative team of laboratory experts and the integrated oversight approach promote knowledge-sharing and accountability to support the application of the GCLP Guidelines and compliance monitoring. The systematic implementation of the integrated laboratory oversight activities helped identify valuable lessons for improving laboratory performance and opportunities to strengthen quality oversight for laboratories participating in clinical research or trials.</p>","PeriodicalId":7544,"journal":{"name":"AIDS research and human retroviruses","volume":" ","pages":"615-621"},"PeriodicalIF":1.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141553946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PET/CT Targeted Tissue Sampling Reveals Intravenously Administered HGN194 IgG1 Affects HIV Distribution after Rectal Exposure.","authors":"Roslyn A Taylor, Sixia Xiao, Ann M Carias, Michael D McRaven, Divya N Thakkar, Mariluz Araínga, Ramon Lorenzo-Redondo, Edward J Allen, Kenneth A Rogers, Sidath C Kumarapperuma, Siqi Gong, Meegan R Anderson, Yanique Thomas, Patrick J Madden, Davide Corti, Elisabetta Cameroni, Antonio Lanzavecchia, Beth Goins, Peter Fox, Francois J Villinger, Ruth M Ruprecht, Thomas J Hope","doi":"10.1089/AID.2024.0019","DOIUrl":"10.1089/AID.2024.0019","url":null,"abstract":"<p><p>Neutralizing monoclonal antibodies hold great potential for prevention of human immunodeficiency virus (HIV) acquisition. IgG is the most abundant antibody in human serum, has a long half-life, and potent effector functions, making it a prime candidate for an HIV prevention therapeutic. We combined Positron Emission Tomography imaging and fluorescent microscopy of ⁶⁴Cu-labeled, photoactivatable-green fluorescent protein HIV (PA-GFP-BaL) and fluorescently labeled HGN194 IgG1 to determine whether intravenously instilled IgG influences viral interaction with mucosal barriers and viral penetration in colorectal tissue 2 h after rectal viral challenge. Our results show that IgG1 did not alter the number of virions found throughout the colon or viral penetration into the epithelium of the rectum or descending colon. A minor increase in virions was observed in the transverse colon of IgG1 treated animals. Overall, the number of viral particles found in the mesenteric lymph nodes was low. However, IgG1 administration resulted in a significant reduction of virions found in mesenteric lymph nodes. Taken together, our results show that HGN194 IgG1 does not prevent virions from penetrating into the colorectal mucosa but may perturb HIV virion access to the lymphatic system.</p>","PeriodicalId":7544,"journal":{"name":"AIDS research and human retroviruses","volume":" ","pages":"637-648"},"PeriodicalIF":1.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11876819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141892654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Receipt of Prostate-Specific Antigen Test in Medicaid Beneficiaries With and Without HIV in 2001-2015 in 14 States.","authors":"Filip Pirsl, Keri Calkins, Jacqueline E Rudolph, Eryka Wentz, Xiaoqiang Xu, Yiyi Zhou, Bryan Lau, Corinne E Joshu","doi":"10.1089/AID.2023.0142","DOIUrl":"10.1089/AID.2023.0142","url":null,"abstract":"<p><p>Studies have reported lower incidence of prostate cancer in men living with HIV compared with men without HIV for reasons that remain unclear. Lower prostate cancer screening in men living with HIV could explain these findings. We describe receipt of prostate-specific antigen (PSA) test each calendar year by HIV status in Medicaid beneficiaries enrolled in 14 U.S. states, 2001-2015. A total of 15,299,991 Medicaid beneficiaries aged 18-64 with ≥7 months of continuous enrollment were included in analyses. HIV diagnosis and PSA tests were identified using non-drug claims. Incidence rate ratios comparing receipt of PSA test by HIV status adjusted for age, race/ethnicity, state of residence, calendar year, comorbid conditions, benign prostatic conditions, and receipt of testosterone-replacement therapy were estimated using Poisson regression. Models were also stratified by state, and estimates were pooled using random-effects meta-analysis to account for heterogeneity by state. Models were additionally stratified by age and race/ethnicity. There were 42,503 PSA tests over 314,273 person-years and 1,669,835 PSA tests over 22,023,530 person-years observed in beneficiaries with and without HIV, respectively. The incidence of PSA test was slightly lower in men living with HIV than men without HIV (incidence rate ratio [IRR] = 0.98; 95% confidence interval [CI]: 0.97, 0.99) when adjusting for state. In the pooled estimate, the rate was higher among men living with HIV (IRR = 1.11; 95% CI: 0.97, 1.27). Pooled estimates indicated approximately equal or higher rates of PSA test in men living with HIV compared with men without HIV across models stratified by age and race/ethnicity groups. Findings do not support the hypothesis that differences in prostate cancer screening explain differences in incidence by HIV status.</p>","PeriodicalId":7544,"journal":{"name":"AIDS research and human retroviruses","volume":" ","pages":"649-658"},"PeriodicalIF":1.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141260836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparing Gold-Standard Sanger Sequencing with Two Next-Generation Sequencing Platforms of HIV-1 <i>gp160</i> Single Genome Amplicons.","authors":"David J Nolan, Jonathan DaRoza, Robin Brody, Krishna Ganta, Katherine Luzuriaga, Chris Huston, Simon Rosenthal, Susanna L Lamers, Rebecca Rose","doi":"10.1089/AID.2024.0012","DOIUrl":"10.1089/AID.2024.0012","url":null,"abstract":"<p><p>Our goal was to assess the accuracy of next generation sequencing (NGS) compared with Sanger. We performed single genome amplification (SGA) of HIV-1 <i>gp160</i> on extracted tissue DNA from two HIV+ individuals. Amplicons (<i>n</i> = 30) were sequenced with Sanger or reamplified with barcoded primers and pooled before sequencing using Oxford Nanopore Technologies (ONT) and Pacific Biosciences (PB). For each amplicon, a consensus sequence for NGS reads was obtained by (1) mapping reads to the Sanger sequence when available (\"reference-based\") or (2) mapping reads to a \"pseudo-reference\" sequence, i.e., a consensus sequence of a subset of NGS reads (\"reference-free\"). PB reads were clustered based on genetic similarity. A Sanger consensus sequence was obtained for 23/30 amplicons, for which all NGS consensus sequences were identical (<i>n</i> = 9) or nearly identical (<i>n</i> = 14) compared with Sanger. For the nine mismatches between Sanger/NGS, the nucleotide in the NGS sequence matched all other sequences from that patient. Of the 7/30 amplicons without a Sanger sequence, NGS sequences had ≥35 ambiguous calls in five amplicons and 0 ambiguities in two amplicons. Analysis of the electropherograms showed failure of a single sequencing primer for the latter two amplicons (consistent with a single template) and overlapping peaks for the other five (consistent with multiple templates). Clustering results closely followed the Sanger/NGS consensus results, where amplicons derived from a single template also had a single cluster and vice versa (with one exception, which could be the result of barcode misidentification). Representative sequences from the clusters contained 2-13 differences compared with Sanger/NGS. In summary, we show that both ONT and PB can produce amplicon consensus sequences with similar or higher accuracy compared with Sanger and, importantly, without the need for a known reference sequence. Clustering could be useful in some circumstances to predict or confirm the presence of multiple starting templates.</p>","PeriodicalId":7544,"journal":{"name":"AIDS research and human retroviruses","volume":" ","pages":"659-669"},"PeriodicalIF":1.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141465488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Knockdowns of CD3zeta Chain in Primary NK Cells Illustrate Modulation of Antibody-Dependent Cellular Cytotoxicity Against Human Immunodeficiency Virus-1.","authors":"Sho Sugawara, Esther Lee, Melissa A Craemer, Alayna Pruitt, Harikrishnan Balachandran, Simon B Gressens, Kyle Kroll, Cordelia Manickam, Yuxing Li, Stephanie Jost, Griffin Woolley, R Keith Reeves","doi":"10.1089/AID.2023.0114","DOIUrl":"10.1089/AID.2023.0114","url":null,"abstract":"<p><p>Multifaceted natural killer (NK) cell activities are indispensable for controlling human immunodeficiency virus (HIV)-1 transmission and pathogenesis. Among the diverse functions of NK cells, antibody-dependent cellular cytotoxicity (ADCC) has been shown to predict better HIV-1 protection. ADCC is initiated by the engagement of an Fc γ receptor CD16 with an Fc portion of the antibody, leading to phosphorylation of the CD3 ζ chain (CD3ζ) and Fc receptor γ chain (FcRγ) as well as downstream signaling activation. Though CD3ζ and FcRγ were thought to have overlapping roles in NK cell ADCC, several groups have reported that CD3ζ-mediated signals trigger a more robust ADCC. However, few studies have illustrated the direct contribution of CD3ζ in HIV-1-specific ADCC. To further understand the roles played by CD3ζ in HIV-1-specific ADCC, we developed a CD3ζ knockdown system in primary human NK cells. We observed that HIV-1-specific ADCC was inhibited by CD3ζ perturbation. In summary, we demonstrated that CD3ζ is important for eliciting HIV-1-specific ADCC, and this dynamic can be utilized for NK cell immunotherapeutics against HIV-1 infection and other diseases.</p>","PeriodicalId":7544,"journal":{"name":"AIDS research and human retroviruses","volume":" ","pages":"631-636"},"PeriodicalIF":1.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141747177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Strengthening the Application of the DAIDS GCLP Guidelines: The Implementation of an Integrated Laboratory Oversight Framework.","authors":"Loc Nguyen, Anne Leach, Estelle Piwowar-Manning, Mark Marzinke, Allan Levesque, Claudine Gregorio, Kristen Skinner, Tiri Towindo, Heidi Hanes, Kwabena Sarpong, Christian Kasongo, Natasha Samsunder, Grace Aldrovandi, Kathie G Ferbas, Andries Engelbrecht, Michael Stirewalt, Emily Anyango, Sasiwimol Ubolyam, Pamela Lankford-Turner, Marcella Sarzotti-Kelsoe","doi":"10.1089/AID.2024.0042","DOIUrl":"10.1089/AID.2024.0042","url":null,"abstract":"<p><p>The Division of AIDS (DAIDS) Good Clinical Laboratory Practice (GCLP) Guidelines establish a framework to guide the oversight of laboratories supporting DAIDS-sponsored clinical research or trials. Compliance with these guidelines promotes data reliability, validity, and safety of the clinical research or trial participants and laboratory staff and ensures adherence to regulatory requirements. Acknowledgment and adoption of the DAIDS GCLP Guidelines are critical in building laboratory capacity and preparedness for conducting clinical trials. In collaboration with DAIDS, laboratory experts support the implementation of the DAIDS Integrated Laboratory Oversight Framework (Framework) activities. This article describes the implementation of the GCLP Guidelines, the Framework activities, and the coordinated efforts to strengthen laboratory performance. The Framework activities include four components: Quality Assurance Oversight, GCLP Audits, GCLP Training, and Laboratory Quality Improvement. Comparison of GCLP Guidelines with other regulations or standards, including U.S. Clinical Laboratory Improvement Amendments regulation 42 CFR 493, College of American Pathologists, World Health Organization GCLP, and International Organization for Standardization, ISO 15189:2012 standards, highlighted the differences and similarities to guide integration and harmonization efforts. Processes related to the Framework activities are outlined in detail, including key data derived from the managed activities of over 175 laboratories worldwide. Via the evolution of the DAIDS GCLP Guidelines and laboratory oversight workflows, the laboratories participating in DAIDS-sponsored clinical research and trials have successfully participated in internal and external regulatory audits. The collaborative and integrated oversight approach promotes knowledge-sharing and accountability to support the implementation of the DAIDS GCLP Guidelines and compliance monitoring. Lessons learned have helped with the implementation of the DAIDS integrated laboratory oversight approach and quality oversight programs at multiple laboratories worldwide.</p>","PeriodicalId":7544,"journal":{"name":"AIDS research and human retroviruses","volume":" ","pages":"622-630"},"PeriodicalIF":1.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141970413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study APV20002: Safety and Efficacy Results Through Week 684 for Pediatric Participants Living with HIV-1 Treated with Ritonavir-Boosted Fosamprenavir Oral Solution-Based Antiretroviral Therapy.","authors":"Lisa L Ross, Mark F Cotton, Haseena Cassim, Harmony P Garges, Sven C van Dijkman, Kishen Morarji, Supriya Karthika, Susan Danehower, Jacob Radford, David Butcher","doi":"10.1089/AID.2024.0020","DOIUrl":"10.1089/AID.2024.0020","url":null,"abstract":"<p><p>APV20002 was a multicenter, international, open-label study that began in 2003 investigating the pharmacokinetics, efficacy, and safety of ritonavir-boosted fosamprenavir (FPV/r) oral solution (OS) in combination with nucleoside reverse transcriptase inhibitor-based antiretroviral therapy (ART) in participants living with HIV-1 aged 4 weeks to <2 years with a primary endpoint at Week 48 (48W). Participants in APV20002 could continue in the study post-48W until FPV OS was locally available in their countries. Children were required to discontinue after reaching >39 kg or if FPV OS had no clinical benefit. Fifty-nine participants were enrolled; 5/59 received a single FPV OS visit for pharmacokinetic determinations. Most (38/54; 70%) were antiretroviral experienced; 39/59 participants had >48 weeks on treatment, 4/39 of whom discontinued after 48 weeks due to an adverse event (AE). At 48W, 88% of participants had HIV-1 RNA <400 copies/mL by Observed analysis; the proportion with HIV-1 RNA <400 copies/mL remained high (84%-100%) through Week 684. The median CD4⁺ cell count was 1,235 cells/mm³ [<i>n</i> = 51] at baseline, 1,690 cells/mm³ (<i>n</i> = 41) at Week 48, and 1,280 cells/mm³ (<i>n</i> = 21) at Week 180. From baseline to Week 684, 54/59 (92%) participants had ≥1 treatment-emergent AE regardless of causality; 42/59 (71%) had a treatment-emergent grade 2-4 AE, predominantly maximum toxicity: grade 2; 21/59 (36%) and 21/59 (36%) had severe or grade 3/4 AEs. From baseline to Week 684, 14/54 (26%) participants met virologic failure (VF) criteria, 9/14 before 48W. HIV from 1/9 VFs through 48W developed treatment-emergent reduced susceptibility to FPV and 1/9 to lamivudine/emtricitabine. Post-48W, 4/5 participants with VF had phenotype results; all were still susceptible to all study drugs at VF. In conclusion, FPV OS-based ART was efficacious and generally well tolerated in this long-running pediatric study through 684 weeks of treatment, with a safety profile consistent with experience in adults and older children.</p>","PeriodicalId":7544,"journal":{"name":"AIDS research and human retroviruses","volume":" ","pages":"606-613"},"PeriodicalIF":1.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141553948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}