Current Opinion in HIV and AIDS

PURPOSE OF REVIEW: We explore the current status of research on HIV-1 subtype-specific variations and their impact on HIV-1 latency. We also briefly address the controversy surrounding the decision-making process governing the ON/OFF states of HIV-1 transcription, specifically focusing on the regulatory elements, the long terminal repeat (LTR), and Tat. Understanding the decision-making process is crucial for developing effective intervention strategies, such as the 'shock-and-kill' approach, to reactivate latent HIV-1...

PURPOSE OF REVIEW: The public health challenge of overweight and obesity increasingly affects people living with HIV (PWH). These effects have also accelerated as the prevalence of antiretroviral therapy (ART) use has increased among PWH. It is therefore also critical that we examine and understand the pathogenesis of obesity among PWH.This review will aim to summarize relevant and recent literature related to the risks of weight gain and obesity associated with HIV disease progression, cardiometabolic disease, and multimorbidity among PWH...

PURPOSE OF REVIEW: HIV epidemics are increasing in many emerging economy countries, whilst the very process of 'economic emergence' is obesogenic. Annual deaths related to obesity and overweight are now four times more than for HIV globally. We describe the intersections between HIV and obesity in emerging economies, and highlight potential mitigation options, including antiobesity medications (AOMs), which are safe and effective, but inaccessibly priced. RECENT FINDINGS: We summarize what is known about weight-change in HIV and review strategies including public health policies and clinical interventions for emerging economy countries to fight obesity...

PURPOSE OF REVIEW: People with HIV (PWH) on antiretroviral therapy (ART) globally are disproportionately affected by obesity, with prevalence rates highest among women with HIV. The purpose of this review is to discuss rates of obesity, factors associated with obesity, and adverse consequences of obesity among PWH. RECENT FINDINGS: Among PWH on ART, rates of obesity have increased over the last several decades and tend to be higher than the general population. Weight gain with the initiation of new ART regimens such as integrase strand transfer inhibitor (INSTI)-based regimens are thought to contribute to higher rates of obesity among PWH on ART...

PURPOSE OF REVIEW: With the introduction of novel and more potent antiretroviral therapies (ART), persons with HIV (PWH) are living longer lives and experiencing higher rates of age- and weight-related comorbidities, including cardiovascular and metabolic diseases. Women with HIV (WWH) experience disproportionate rates of obesity, as evidenced by longitudinal observational cohorts both in the United States and globally. RECENT FINDINGS: In this article, we aim to review major research findings regarding WWH and obesity over the past few years...

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PURPOSE OF REVIEW: Design of an HIV vaccine that can induce broadly neutralizing antibodies (bnAbs) is a major goal. However, HIV bnAbs are not readily made by the immune system. Rather HIV bnAbs are disfavored by a number of virus and host factors. The purpose of the review is to discuss recent progress made in the design and use of immunogens capable of inducing HIV bnAbs in the Duke Consortia for HIV/AIDS Vaccine Development. RECENT FINDINGS: New immunogens capable of binding with high affinity to unmutated common ancestors (UCAs) of bnAb B cell lineages have been designed and strategies for stabilization of HIV Env in its prefusion state are being developed...

PURPOSE OF REVIEW: Recent advances in the understanding of the difficult immunologic requirements for the induction of broadly neutralizing antibodies for HIV have spurred interest in optimizing vaccine approaches intended to stimulate a robust germinal center reaction. In preclinical models, techniques to optimize the germinal center response have included alterations in the timing, dose, and delivery method of immunogens and have resulted in substantially enhanced germinal center responses in lymph nodes and neutralizing antibodies in serum...

PURPOSE OF REVIEW: There is growing consensus that eliciting CD8+ T cells in addition to antibodies may be required for an effective HIV vaccine for both prevention and cure. Here, we review key qualities of vaccine-elicited CD8+ T cells as well as major CD8+ T cell-based delivery platforms used in recent HIV vaccine clinical trials. RECENT FINDINGS: Much progress has been made in improving HIV immunogen design and delivery platforms to optimize CD8+ T cell responses...

PURPOSE OF REVIEW: In the past two decades, there has been an explosion in the discovery of HIV-1 broadly neutralizing antibodies (bnAbs) and associated vaccine strategies to induce them. This abundance of approaches necessitates a system that accurately and expeditiously identifies the most promising regimens. We herein briefly review the background science of bnAbs, provide a description of the first round of phase 1 discovery medicine studies, and suggest an approach to integrate these into a comprehensive HIV-1-neutralizing vaccine...

PURPOSE OF REVIEW: Ending the HIV epidemic will require the development of additional effective immune-mediated and nonimmune-mediated means of HIV prevention. Evaluating novel interventions requires large, controlled trials demonstrating efficacy. Recent advances in the field of HIV prevention necessitate new approaches to efficacy trial design. RECENT FINDINGS: Three classes of efficacy trial designs are possible: standard of prevention-controlled trials, active-controlled trials, and active-controlled trials augmented with external control data...

PURPOSE OF THE REVIEW: Nonhuman primates (NHPs) are seen as the closest animal model to humans in terms of anatomy and immune system makeup. Here, we review how preclinical studies in this model system are teaching the field of HIV vaccinology the basic immunology that is needed to induce broadly neutralizing antibodies (bnAbs) with vaccination and elicit protective T cell responses. These lessons are being translated into clinical trials to advance towards protective active vaccination against HIV-1 infection...

PURPOSE OF REVIEW: There is a need to conduct multiple experimental medicine trials in regions with significant burden of disease to ensure the global relevance of vaccines under development including the African context. RECENT FINDINGS: African scientists can support accelerated HIV vaccine development by leading EMVTs in the region in a complementary fashion to global efforts and augment evidence generated to optimize and advance relevant vaccines towards licensure...

PURPOSE OF REVIEW: Explore whether immunization with germline-targeting Env immunogens during ART, followed by ATI, leads to the identification of viral envelope glycoproteins (Envs) that promote and guide the full maturation of broadly neutralizing antibody responses. RECENT FINDINGS: The HIV-1 envelope glycoprotein (Env) does not efficiently engage the germline precursors of broadly neutralizing antibodies (bnAbs). However, Env-derived proteins specifically designed to precisely do that, have been recently developed...

PURPOSE: Active and passive immunization strategies are challenged by the extraordinary diversity of HIV, and the need for high titers of neutralizing antibodies to confer protective immunity. This review summarises recent studies and the barrier that these interventions will need to overcome to prevent viral resistance. RECENT FINDINGS: Studies from the antibody mediated prevention trial identified a measure of protective titers, finding that higher titers than anticipated will be needed to prevent infection...

PURPOSE OF REVIEW: The improved health of persons with HIV (PWH) resulting from antiretroviral therapy (ART) has led to recommendations for reduced laboratory monitoring. We studied, for all PWH in care over 20 years at the Southern Alberta Clinic (SAC), Canada, the changing use and results of HIV-specific laboratory testing [i.e., CD4+ testing, plasma HIV viral load (PVL), and genotypic antiretroviral resistance testing (GART)].In this descriptive retrospective longitudinal cohort observational study, we examined HIV-specific laboratory testing for all PWH from 2000 to 2020 within the context of HIV-related health outcomes, program costs, and mortality...

PURPOSE OF REVIEW: This review highlights advances in HIV transcription and epigenetic latency mechanisms and outlines current therapeutic approaches to eliminate or block the HIV-1 latent reservoir. RECENT FINDINGS: Novel host factors have been reported to modulate HIV-1 transcription and latency. Chromatin affinity purification strategies followed by mass spectrometry (ChAP-MS) identified the chaperone protein p32 to play an important role in HIV-1 transcriptional regulation via interactions with the viral transcriptional activator Tat...

PURPOSE OF REVIEW: CD8+ T cell responses are a key component of the host immune response to human immunodeficiency virus (HIV) but vary significantly across individuals with distinct clinical outcomes. These differences help inform the qualitative features of HIV-specific CD8+ T cells that we should aim to induce by vaccination. RECENT FINDINGS: We review previous and more recent findings on the features of dysfunctional and functional CD8+ T cell responses that develop in individuals with uncontrolled and controlled HIV infection, with particular emphasis on proliferation, cytotoxic effector function, epitope specificity, and responses in lymph nodes...

PURPOSE OF REVIEW: The success of HIV-1 eradication strategies relies on in-depth understanding of HIV-1-infected cells. However, HIV-1-infected cells are extremely heterogeneous and rare. Single-cell multiomic approaches resolve the heterogeneity and rarity of HIV-1-infected cells. RECENT FINDINGS: Advancement in single-cell multiomic approaches enabled HIV-1 reservoir profiling across the epigenetic (ATAC-seq), transcriptional (RNA-seq), and protein levels (CITE-seq)...