Current Opinion in HIV and AIDS

Current Issue Highlights

Development of adjuvanted HIV vaccines tailored for early life: immunologic rationale, clinical experience, and future directions
November 2026: 21(6):488-498
Purpose of review
This review highlights the rationale for and clinical experience in advancing age-specific adjuvantation systems to develop well tolerated and effective pediatric HIV vaccines.
Recent findings
Due to both cellular and soluble factors, infant immunity is distinct from that of older children and adults, featuring Th2 bias, tolerogenic APC programming, and reduced Tfh support. Due to distinct functional responses downstream of pattern recognition receptor signaling, adjuvant action is age-specific. Despite a growing pipeline of adjuvants and increasing interest in developing early-life immunization strategies against HIV, few adjuvants have been rigorously evaluated for use in pediatric HIV vaccines. In line with FDA Modernization Act 2.0, systems vaccinology and age-specific immunoprofiling in vivo and in vitro can inform down selection and optimization of age-specific adjuvanted HIV vaccine formulations. Several adjuvants have been assessed as components of HIV vaccines in infants including Alum, the oil-in-water emulsion MF59 and the TLR4 agonist glucopyranosyl lipid A (GLA).
Summary
There is strong rationale to develop an infant HIV vaccine to provide early-life protection, and several adjuvants have been assessed thus far in early-phase clinical studies. With a growing adjuvant pipeline, much work remains to assess which adjuvants should be advanced for an infant HIV vaccine. Leveraging age-specific preclinical studies including immune profiling and human in-vitro modeling can inform down selection to identify adjuvantation systems offering safety and antigen dose sparing, while enhancing breadth and durability of vaccine immunogenicity.
Weight gain, adipose tissue remodeling and cardiometabolic disease in people with HIV
November 2026: 21(6):480-487
Purpose of review
Weight gain and associated adipose tissue remodeling have been partly linked to HIV infection and to some current antiretroviral therapy (ART) regimens in ART-naive and ART-controlled people with HIV (PWH). This review addresses recent findings on adipose tissue distribution and remodeling in PWH, receiving dolutegravir, bictegravir and/or tenofovir alafenamide (TAF), highlighting how visceral adiposity contributes to cardiometabolic comorbidities.
Recent findings
Preclinical models exposed to dolutegravir, bictegravir, tenofovir disoproxil fumarate (TDF) and/or TAF demonstrate alterations in adipose tissue, including mitochondrial dysfunction, fibrosis, inhibited beiging, and insulin resistance. Transcriptomic studies of abdominal subcutaneous fat from ART-controlled PWH further revealed elevated inflammation, fibrosis and insulin resistance. Increased visceral adiposity raises the risk of cardiometabolic disorders such as insulin resistance and diabetes, metabolic-dysfunction-associated steatotic liver disease and cardiovascular diseases. Reversing weight gain linked to ART, by switching regimens or adding antiobesity medications like the GLP-1 receptor agonist semaglutide, has shown potential in reducing adipose tissue remodeling, visceral adiposity and cardiometabolic risk factors.
Summary
Weight gain and increased visceral adiposity partly driven by some ARTs are associated with higher cardiometabolic risk. HIV and ART can either activate or suppress the fat beiging/browning phenotype. Reversing weight gain and visceral adiposity in at-risk PWH is a critical clinical goal.
Reframing obesity in aging people with HIV: sarcopenic obesity, muscle quality, and frailty
November 2026: 21(6):473-479
Purpose of review
As people with HIV (PWH) age, obesity is increasingly prevalent, yet body weight alone inadequately captures the functional and metabolic consequences of adverse body composition remodeling. This review examines emerging evidence supporting a shift from weight-centric approaches toward a framework centered on sarcopenic obesity, muscle quality, and frailty in aging PWH.
Recent findings
Weight gain in the contemporary antiretroviral therapy era often reflects increased visceral and ectopic adiposity. Sarcopenic obesity is a clinically relevant phenotype characterized by the coexistence of excess adiposity and impaired muscle mass or function, with important implications for healthy aging. Emerging evidence highlights myosteatosis and impaired muscle quality as potential mechanistic links between adiposity and functional decline. Exercise-based interventions, particularly those incorporating resistance training, demonstrate promise for preserving physical function, reducing frailty, and improving body composition. In contrast, pharmacologic weight loss may raise concerns regarding lean tissue preservation if implemented without a concurrent focus on muscle health.
Summary
Obesity in aging PWH should be reframed as a body composition and functional health problem rather than simply excess body weight. Clinical and research priorities should emphasize early identification of vulnerability, preservation of muscle health, and interventions that support long-term physical resilience and independence.
The next frontier: AI, multi-omics, and predictive models for weight gain in HIV
November 2026: 21(6):467-472
Purpose of review
People with HIV (PWH) are increasingly susceptible to excess weight gain and obesity after initiation of antiretroviral therapy. However, there is substantial variation in individual weight gain that is difficult to predict with clinical factors alone. We review emerging methods in machine learning and multi-omics that address the biology and prediction of weight gain and weight-associated conditions, persistent challenges, and future directions.
Recent findings
PWH continue to have increasing burden of excess weight gain and obesity. Obesity has a complex pathophysiology with an interplay between biological and environmental factors that make weight gain prediction challenging. Few studies in PWH have used omics or machine learning to capture weight gain trajectories. These studies highlight the promise and challenges of leveraging multi-omics and machine learning for modeling weight gain.
Summary
Advances in machine learning and scalable multi-omics have accelerated research defining pathways of human health and disease. These tools may have an important role in defining the biology and predictors of weight gain in PWH, ultimately to improve risk stratification and identify targeted interventions to improve health outcomes in PWH.
Weight gain in people with HIV in Africa and Asia: a review of causes, consequences, and management implications
November 2026: 21(6):460-466
Purpose of review
To examine weight gain epidemiology in people with HIV (PLWH) across Africa and Asia, focusing on data published in the preceding 18 months, and to identify clinical and programmatic implications, acknowledging that regionally derived evidence remains sparse.
Recent findings
New population-level data from East Africa demonstrate that the nutrition transition is accelerating faster than ART-related weight gain. Thus, HIV-negative individuals gained more weight than PLWH on ART over the transition to dolutegravir regimens in rural Kenya and Uganda. In Asian cohorts, men gained more weight than women after ART initiation. This is the reverse of the sex-specific changes in body weight seen in Africa, and this is particularly worrisome because standard BMI thresholds systematically underestimate cardiometabolic risk in this population. Programmatic data from Uganda have shown that dolutegravir exposure doubles the risk of incident hypertension even after adjustment for BMI change. ART switch trials conducted in high-income settings (DEFINE, ACTG A5391) confirm that regimen changes do not reverse established obesity; however, emerging data from a South African randomized trial (Opti-DOR) suggest that regimen at ART initiation influences weight trajectory. GLP-1 therapies demonstrate compelling efficacy for both weight loss and cardiometabolic health improvement in PLWH, including in Africa, but remain economically inaccessible.
Summary
Weight gain in people with HIV in Africa and Asia reflects the convergence of the nutrition transition, ART pharmacology, and immune reconstitution, disproportionately affecting women in African cohorts and men in Asian cohorts. Cardiometabolic consequences, particularly hypertension, are now robustly documented in African programmatic data, but equivalent evidence from Asia remains sparse. Switching ART does not reverse established obesity, although regimen choice at initiation influences weight trajectory. Access to antiobesity medications may be the defining health policy challenge for these populations over the next decade.

Latest Articles

Immune cell phenotypes across tissues in people with HIV
Current Opinion in HIV and AIDS. October 27, 2026
Purpose of review
This review summarizes our current understanding of immune cell phenotypes across human tissues in the context of HIV infection, with particular emphasis on insights from postmortem studies.
Recent findings
Rapid autopsy cohorts enable systematic collection of multiple anatomical sites within hours of death, including tissues inaccessible during life. Together with biopsy studies, these approaches have revealed tissue-specific phenotypes and functions of HIV-susceptible cells, of long-lived HIV reservoir cells that are the main barrier to cure, and of CD8⁺ T cells and NK cells as effectors that can recognize and eliminate HIV-infected cells.
Summary
Immune cell phenotypes relevant to HIV susceptibility, persistence, and antiviral control diverge across anatomical sites and differ substantially from their counterparts in peripheral blood.
Central nervous system reservoirs and neuroHIV: lessons from rapid research autopsy studies
Current Opinion in HIV and AIDS. October 19, 2026
Purpose of review
Tissue HIV-1 (HIV) reservoirs, particularly within the central nervous system (CNS), remain understudied because of limited access to well preserved human tissues. This review aims to highlight insights from rapid research autopsy studies into HIV persistence in the CNS, with a particular focus on viable-cell approaches, BMCs/microglia as cellular reservoirs, and the mechanisms underlying HIV latency and neuroinflammation. We also discuss key knowledge gaps and how these approaches may inform strategies to target CNS HIV reservoirs.
Recent findings
Recent rapid research autopsy studies demonstrate the value of combining tissue-based assays, viable CNS cell approaches, and advanced multiomics to investigate CNS HIV reservoirs, latency, viral–host interactions, and neuropathogenesis. Brain myeloid cells (BMCs)/microglia appear to be major CNS reservoirs that can harbor inducible, replication-competent HIV during suppressive ART, with latency regulated largely by epigenetic mechanisms. Persistent HIV transcription is associated with IFN-I signaling activation and neuroinflammation, potentially contributing to synaptic dysfunction and neuronal injury underlying HIV-associated neurocognitive disorders (HAND).
Summary
HIV persists in the CNS despite durable ART, with BMCs/microglia emerging as key reservoirs and potential targets for HIV cure strategies. The roles of CNS T cells, astrocytes, and pericytes as bona fide reservoirs remain to be established. Rapid-autopsy programs have enabled complementary tissue-based, viable-cell, phylogenetic, and multiomic approaches to resolve the complexity of CNS HIV persistence. Emerging evidence further links epigenetically regulated HIV latency and persistent IFN-I signaling to HIV reservoir maintenance and CNS injury. Future integration of viable-cell and spatial approaches with longitudinal clinical data will be critical for defining reservoir interactions and developing strategies to eliminate CNS HIV.
The interaction of comorbidities, aging, and HIV persistence in tissues
Current Opinion in HIV and AIDS. October 09, 2026
Purpose of review
The review examines the how the HIV reservoir and its tissue distribution intersect with aging and comorbidity development in people with HIV (PWH) on suppressive antiretroviral therapy (ART) and considers implications for cure-directed research in an aging population.
Recent findings
PWH on ART carry a disproportionate and accelerating comorbidity burden, with multimorbidity projected to rise from 63 to 70% by 2030. Neurocognitive disorders, liver disease, lung disease, cardiovascular disease, and frailty are all elevated, and linked to the viral reservoir through chronic inflammation and direct viral mechanisms. Coinfections (HCV, HBV, CMV) compound this issue by amplifying the reservoir while independently driving the same comorbidities, particularly liver disease, and cardiovascular and frailty outcomes.
Summary
Reservoir persistence and comorbidity burden in aging PWH are mechanistically intertwined, with chronic inflammation as a common driver. These findings underscore the need for longitudinal, tissue-resolved studies spanning the lifespan, as well as inclusion of aged and comorbid individuals in cure-directed trials, given that immune-engagement-dependent cure strategies may exhibit differential efficacy in this growing population.