AIDS Research and Human Retroviruses

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...

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...

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 (PET) imaging and fluorescent microscopy of 64Cu-labeled, photoactivatable-GFP 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 two hours after rectal viral challenge...

The recently FDA-approved cabotegravir has demonstrated efficacy as an antiretroviral agent for HIV treatment and prevention, becoming an important tool to stop the epidemic in the USA. However, the effectiveness of cabotegravir can be compromised by the presence of specific integrase natural polymorphisms, including T97A, L74M, M50I, S119P, and E157Q, particularly when coupled with the primary drug resistance mutations G140S and Q148H. Cabotegravir's recent approval as a pre-exposure prophylaxis may increase the number of individuals taking cabotegravir, which, at the same time, could increase the number of epidemiological implications...

OBJECTION: To assess the causal effect of syphilis on HIV infection by Mendelian randomization analysis. METHODS: The data of syphilis and HIV infection were obtained from genome-wide association studies, Mendelian randomization analyses were conducted using methods such as weighted median, MR Egger, and inverse variance to evaluate the causal relationship between syphilis and HIV infection. Gene expression data of persons living with HIV (PLWH) and single-cell RNA sequencing profiles were obtained from the GEO database...

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 (1-3). ADCC is initiated by the engagement of an Fcg receptor CD16 with an Fc portion of the antibody, leading to phosphorylation of the CD3z chain (CD3) and Fc receptor g chain (FcRg) as well as downstream signaling activation...

Cytokines are key mediators of immune regulation, orchestrate communication between immune cells, and play a pivotal role in shaping the immune landscape during chronic infection and cancer. The therapeutic potential of IL-15/IL-15Rα and IL-12 has been explored individually in various immunotherapeutic strategies, though not as a combination. Therefore, we investigated whether the combination of IL-15/IL-15Rα and IL-12 treatment would enhance the potency and quality of either NK cells, SIV-specific CD8 T cells, or both, compared to single cytokine treatment...

Objectives 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 treatment (ARV), 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 to a large proportion of ARV dispensation in the country...

The border areas of Yunnan Province in China are severely affected by human immunodeficiency virus (HIV). To investigate the risk of HIV transmission and assess the prevalence of pretreatment drug resistance (PDR) in the border area, blood samples were collected from individuals with newly reported HIV in 2021 in three border counties (Cangyuan, Gengma, and Zhenkang) in Yunnan Province. Among the 174 samples successfully genotyped, eight circulating recombinant forms (CRFs), two subtypes, and several unique recombinant forms (URFs) were identified...

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...

Continuous recombination and variation during replication could lead to rapid evolution and genetic diversity of HIV-1. Some studies had identified that it was easy to develop new recombinant strains of HIV-1 among the populations of men who have sex with men (MSM). Surveillance of genetic variants of HIV-1 in key populations was crucial for comprehending the development of regional HIV-1 epidemics. The finding was reported the identification of two new unique recombinant forms (URF 20110561 and 21110743) from individuals infected with HIV-1 in Tongzhou, Beijing in 2020-2022...

Transgender women are disproportionately burdened by HIV. Though there is a substantial body of research exploring barriers and facilitators of HIV prevention among transgender women, many barriers remain unaddressed. This study identifies strategies to make HIV prevention trials more congruent with transgender women's preferences and needs to boost trials participation and ultimately enhance initiation and uptake of PrEP. We conducted in-depth interviews (IDIs) with 15 sexually active, HIV-negative transgender women in New York City to understand: (1) preferences concerning long-acting injectable cabotegravir (CAB-LA) for PrEP, and (2) ideas on how to make HIV prevention trial environments more comfortable...

BACKGROUND AND OBJECTIVE: Human T-cell lymphotropic virus type 1 (HTLV-1) is associated with adult T-cell leukemia/lymphoma (ATLL), a fetal malignant infection. Recently, The HTLV-1 new Asymptomatic careers (ACs) have frequently been reported among blood donors. Reaching the profound concept of HTLV-1-associated molecular pathogenesis could result in finding novel therapeutic strategies. The current study aimed to determine leukemia-related signaling regulation in ATLL. MATERIALS AND METHOD: 30 participants were evaluated in three groups, including 10 ATLL patients, 10 ACs, and 10 normal controls...

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, 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...

INTRODUCTION: As the number of older people with HIV (PWH) grows, accidental falls and their associated negative health outcomes are of increasing concern. Fall risk can be measured using novel screening tools such as evaluating postural stability using force plate technology. The aims of this study were to test this technology to assess fall risk among older PWH. METHODS: In a cross-sectional, observational study of people with and without (PWoH) with a range of fall risk, participants underwent balance assessment using the validated BTrackS balance plate...

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...

HIV-1 is characterized by remarkable genetic diversity resulting from its high replication rate, error-prone reverse transcriptase enzyme and recombination events. In Uganda, HIV-1 subtype diversity is mostly dominated by subtypes A, D, and A1/D Unique Recombinant Forms (URFs). In this study, deep sequences of HIV from patients with known antiretroviral therapy (ART) status were analyzed to determine the subtypes and to identify drug-resistance mutations circulating in the study population. Of the 187 participant samples processed for next-generation sequencing (NGS), 137 (73%) were successfully classified...

BACKGROUND: When an initial antiretroviral (ART) regimen is effective and well-tolerated, it can be maintained for years as long as the patient adheres. Prior research has revealed that shorter initial ART duration is associated with regimen type, female sex, injection drug use (IDU) as the HIV transmission risk factor, and lower baseline CD4 count. We examined initial ART duration in ART-naïve individuals newly enrolling in HIV care in the DC Cohort. METHODS: We included ART naïve-individuals with detectable HIV RNA enrolled in the DC Cohort after January 2011 with >6 months of follow-up...

Our goal was to assess the accuracy of next generation sequencing (NGS) compared to Sanger. We performed single genome amplification (SGA) of HIV-1 gp160 on extracted tissue DNA from two HIV+ individuals. Amplicons (n=30) were sequenced with Sanger, or re-amplified with barcoded primers and pooled before sequencing using Oxford Nanopore Technologies [ONT] and Pacific Bioscience [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...

OBJECTIVE: The objective of this study was to estimate the structure and relationships between four hypothesized frailty dimensions (physical, emotional, cognitive, and social) and the extent to which personal and HIV-related factors and comorbidity associate with these frailty dimensions. DESIGN AND METHODS: This is a secondary analysis of an existing dataset arising from Positive Brain Health Now (+BHN) study (n=856) in people aging with HIV (mean age: 52.3±8...