This review summarizes the epidemiology of Cytomegalovirus infections in children exposed to or infected with HIV and the impact of CMV infection on overall health outcomes in this population. CMV infections and cCMV remain a significant burden in HIV exposed and HIV infected children requiring close long-term follow-up. While CMV disease occurs rarely in HIV-infected individuals in the ART-era, the complex interplay between CMV and HIV could have a major impact on childhood health outcomes in HIV-infected and exposed children. Congenital CMV infection (cCMV) is well recognized as the most common congenital viral infection and the leading cause of sensorineural hearing loss (SNHL). CMV-HIV co-infections have been shown to increase the incidence of cCMV, but effect on long-term outcomes remains largely undetermined at this time.
The central nervous system (CNS) remains a relatively understudied reservoir of HIV that may have significant implications for HIV cure and the pathogenesis of cognitive disorders that persist despite viral suppression with antiretroviral therapy (ART). This review will describe our current understanding of the nature, size and composition of the CNS reservoir and the possible contribution of viral persistence in the CNS on viral replication, neuroinflammation and cognitive disease. Reservoirs of intact and defective HIV proviral DNA have recently been detected in both the brain parenchyma and cerebrospinal fluid (CSF) of ART-suppressed PWH. Moreover, viruses from these sites are transcriptionally and translationally active, with the potential to propagate infection ex vivo in the absence of ART. Ongoing viral persistence likely contributes to elevated risk of comorbid neurocognitive issues and measures of neuroinflammation support a pathological impact of HIV reservoirs on the brain. However, it is becoming clear that the sub-regions of the CNS including the brain parenchyma and CSF contain unique reservoir characteristics including cellular sources and reservoir dynamics which likely impart different effects on neuropathology. The CNS represents a heterogeneous reservoir of HIV with sub-regional differences in reservoir maintenance and cellular sources, highlighting the need to consider these nuances in HIV treatment, neuropathology and cure strategies.
This review discusses recent advances in understanding the mechanisms of CNS HIV invasion and persistence and examines how these processes relate to the neurologic complications of HIV. Recent studies have provided compelling evidence that HIV can persist within CNS macrophages and microglia despite long-term suppressive ART, supporting the existence of a CNS reservoir. Updates to treatment of neurosymptomatic CSF HIV RNA escape include evaluation of CNS-specific drug resistance patterns and ART optimization. Evaluation of cognitive symtpoms in persons with HIV should include a comprehensive medical and neurologic evaluation, cessation of Efavirenz, and evaluation of HIV disease activity and immune dysregulation. Novel HIV cure strategies, including shock-and-kill approaches, block-and-lock strategies, and broadly neutralizing antibodies have highlighted the importance of understanding CNS reservoir dynamics and potential neurotoxicity when designing HIV cure strategies. HIV enters the CNS during early infection and may establish a persistent viral reservoir. CNS HIV persistence has important clinical implications, including symptomatic CSF HIV RNA escape and cognitive dysfunction, and may represent a barrier to HIV cure.
This review examines emerging PrEP delivery models designed to expand access to HIV prevention outside of traditional clinic settings. It aims to synthesize recent evidence from these models on PrEP uptake, acceptability, and persistence, as well as geographic, social, and structural challenges, drawing on both the research literature and insights from recent programs. Recent studies have highlighted the potential of decentralized PrEP delivery approaches, including community-based distribution, pharmacy-based PrEP provision, telePrEP, and automated PrEP dispensing. These models can improve access, reduce stigma, and provide more personalized care. Hybrid approaches and integration of digital tools and peer support have also shown promise in enhancing adherence and retention. However, challenges related to effectiveness, scalability, regulatory constraints, and cost-effectiveness remain. Decentralized PrEP delivery models offer flexible, client-centered solutions that can significantly expand access to HIV prevention for vulnerable groups. Future research should focus on implementation and policy innovation to support integratration of these models into existing health systems and reach underserved populations.
With the widespread availability of effective antiretroviral therapy, the spectrum of cognitive impairment in people with HIV has changed from a subcortical dementia to milder impairment. The 2007 criteria for HIV-associated neurocognitive disorders (HAND) provided a methodological approach to classify milder and asymptomatic forms. Research using these criteria found that around 45
Purpose of the Review This review examines the multifaceted barriers and facilitators influencing PrEP uptake among priority populations, including MSM, PWUD, sex workers, transgender individuals, and AGYW, with a focus on generating actionable recommendations for governments, providers, and community organisations to scale effective HIV prevention models globally. Recent Findings Despite PrEP's proven efficacy, uptake remains constrained by intersecting individual, provider, structural, and systemic barriers. Key challenges include limited awareness, misinformation, provider-level stigma, structural discrimination, legal repression, prohibitive costs, and healthcare inaccessibility, burdens that fall disproportionately on priority populations in low- and middle-income countries. Conversely, evidence from sub-Saharan Africa, Asia, Europe, and the Americas demonstrates that community-led awareness campaigns, integration of PrEP into sexual and reproductive health services, long-acting injectable formulations, mobile clinics, peer support structures, and digital health and telemedicine tools meaningfully improve access and adherence, particularly among youth and rural populations. Policy-level interventions, including decriminalisation of sex work, same-sex relationships, and drug use, alongside subsidised access and inclusion in universal health coverage frameworks, are identified as critical enablers of equitable reach. Summary Achieving global HIV prevention targets requires more than biomedical innovation. This review underscores that rights-based, community-embedded, and culturally affirming strategies paired with structural reform and sustained investment are essential to expanding PrEP access and equity. PrEP must be positioned not merely as a clinical tool, but as a cornerstone of an equity-driven HIV prevention architecture.
To provide a summary of epigenetic studies of HIV with a focus on DNA methylation-based biomarkers of aging. We examine first, second, and third generation epigenetic clocks, and how these biomarkers relate to molecular and phenotypic outcomes in people with HIV (PWH). Current studies show novel associations of epigenetic aging with cellular senescence, human endogenous retroviruses and transposable elements, metabolic changes, neurological injury, and sex-based aging differences in PWH. First-generation epigenetic clocks of chronological age show an average of 5–7 years of age acceleration in PWH compared to people without HIV. Second-generation epigenetic clocks demonstrate accelerated aging-related phenotypes in PWH, including greater predicted morbidity and mortality. Third-generation epigenetic clocks provide novel insights into mechanisms of aging including DNA damage and beneficial adaptations, human endogenous retroviruses and transposable DNA elements, and distinct aging patterns in different organ systems. Epigenetic clocks offer the promise of accurate, quantitative biological markers of aging in research and clinical settings for PWH.
This paper explores how womanist theory. a framework grounded in the lived experiences, cultural knowledge, and spiritual traditions of Black women, can enhance HIV implementation science. We ask: How can womanist theory advance more equitable, effective, and culturally congruent HIV prevention, care, and treatment for Black women? Black women account for 55
The HIV-1 pandemic is characterized by extensive viral genetic diversity, with strains that can be classified into distinct clades or subtypes based on sequence relatedness. Biological differences between subtypes have also been reported. HIV-1 subtype B, predominant in North America and Europe is most studied, but non-B subtypes represent the majority of infections globally and in sub-Saharan Africa, which accounts for more than two-thirds of people living with HIV. Whereas the implications of genetic and biological diversity overall for HIV prevention, treatment and cure strategies are recognized, the impact of clade differences is contested. Here we review how viral and host diversity, including subtype-specific differences may shape HIV pathogenesis, reservoir characteristics and cure strategies, highlighting data from regions where non-B subtypes circulate. Studies from African and global cohorts highlight differences in epidemiological spread and disease progression among HIV-1 subtypes that may be attributed to viral genetic sequence variations and resultant distinct properties in viral replication capacity, immune evasion, interferon resistance, co-receptor usage, latency regulation and reservoir biology. HIV-1 diversity has implications for virus biology, transmission and clinical outcomes. Clade-specific differences therefore warrant consideration in the development and design of prevention, treatment and cure strategies, including diagnostic and monitoring assays. Incorporating multi-clade research and regionally relevant cohorts will advance and accelerate efforts toward a universally applicable HIV cure.
Weight gain and development of obesity has been well-described with contemporary antiretroviral therapy (ART), and management has proven difficult. It remains unclear whether weight gain can be mitigated or reversed by switching ARV classes. We aim to summarize recent literature on ART switch to attenuate weight gain. Recent studies have recognized integrase strand transfer inhibitors (INSTI) and tenofovir alafenamide (TAF) as significant independent contributors to weight gain. The mechanisms for weight gain may stem from adipose tissue hypertrophy and fibrosis. The reversibility of the weight gain appears to be limited, with trials evaluating switching to more “weight-neutral” ART not proving effective. Discontinuing INSTI- and/or TAF-based regimens has not led to significant changes in weight, suggesting that alternative strategies may be required to modify weight trajectories in individuals who experience excessive weight gain after initiating INSTI-based ART.
HIV further complicates the already complex clinical course of chronic HBV infection. Here we present a personal view of the current state of HBV-specific T-cell immunology and key questions about how T-cell immunity is altered during HBV/HIV co-infection. While HIV usually exacerbates liver disease and increases mortality, higher rates of HBV functional cure – defined as HBsAg loss – are observed after initiation of antiretroviral therapy compared to HBV monoinfection. This creates an exciting opportunity to observe the mechanisms of HBV control during treatment induced immune reconstitution in real time. We discuss how HIV-induced immune CD4 depletion and altered CD8 T-cell differentiation might intersect in distinct ways with the complex natural history of chronic hepatitis B and the different scenarios of co-infection. We also propose how innovative T-cell studies applied to well-designed prospective co-infection cohorts could dramatically enhance our insights into the mechanisms of HBV control and persistence and inform development of novel immunotherapies for people living with HBV and HIV.
Cytomegalovirus (CMV) infection is nearly universal among people with HIV (PWH) and contributes to chronic inflammation, immune senescence, and accelerated biological aging despite suppressive antiretroviral therapy (ART). This review summarizes recent advances in understanding the role of CMV in multimorbidity and aging in PWH, focusing on immune and tissue-based mechanisms, comorbidities, and emerging interventions. CMV reactivation drives clonal T-cell expansion, innate immune reprogramming, adipose tissue inflammation, metabolic rewiring, and durable cellular epigenetic changes that amplify risks for vascular disease, frailty, brain health disorders, diabetes mellitus, and cancer. Early interventional data indicate that letermovir can reduce inflammation and improve immune and frailty outcomes in PWH, while vaccines are advancing in clinical evaluation. CMV is a modifiable driver of immune dysfunction and aging in PWH. Targeted antiviral, vaccine, and host-directed approaches may reduce multimorbidity and promote healthy aging, particularly in populations at greatest risk. Cytomegalovirus (CMV) is nearly universal among people with HIV (PWH) and persists despite suppressive antiretroviral therapy (ART), driving chronic immune activation and accelerated biological aging. CMV is mechanistically linked to clonal T-cell expansion, innate immune reprogramming, metabolic rewiring, and durable epigenetic imprinting. Clinical consequences span multiple aging-related disorders, including frailty cardiovascular disease (CVD), cognitive decline, diabetes mellitus, and cancer. Therapeutic strategies under evaluation include anti-CMV drugs like letermovir and vaccines. Future directions emphasize precision, multimorbidity-focused interventions to extend healthspan in aging PWH.
Antiretroviral therapy (ART) has transformed HIV from a fatal disease into a manageable condition by effectively suppressing viral replication. However, ART does not eradicate HIV due to the persistence of latent reservoirs—mainly replication-competent proviruses in resting CD4⁺ T cells and tissue sanctuaries—that reignite infection upon treatment interruption. This review examines how ART timing and duration influence the size, composition, and stability of the HIV reservoir. Initiating ART during acute infection limits reservoir seeding, reduces genetic diversity, and promotes faster decay of intact proviruses compared to delayed ART, which permits widespread viral integration into long-lived memory T cells and clonal expansion of replication-competent viruses. Anatomical sites such as lymph nodes, gut-associated lymphoid tissue, and the central nervous system act as critical reservoir niches. These insights are central to current HIV cure efforts, which aim for either a sterilizing cure (complete eradication of the virus) or a functional cure (durable remission without ART). Cure strategies—such as “shock-and-kill,”“block-and-lock,” gene editing, and immunotherapy—are being optimized based on reservoir dynamics. Evidence suggests that early-treated individuals, with smaller and more homogeneous reservoirs, are better candidates for these interventions. Although no strategy has yet achieved a cure, combining early ART with targeted interventions may improve outcomes. Understanding how ART influences reservoir dynamics is essential for developing effective HIV cure strategies. We emphasize the importance of prioritizing early-treated individuals in cure trials and advocate for integrated therapeutic approaches to achieve lasting viral remission or complete eradication.
People living with HIV (PLWH) on contemporary antiretroviral therapy experience high rates of overweight/obesity, which predisposes to cardiometabolic disease and multiple other conditions with negative health consequences in this aging population. We aim to summarize the epidemiology and pathophysiology of obesity in PLWH and review recent advances in the therapeutic management of obesity. The prevalence of overweight/obesity in PLWH mirrors long-standing trends in the general population. Obesity and weight gain have a complex, multifactorial pathogenesis and directly mediate detrimental metabolic changes that are common in PLWH. While lifestyle changes are important, surgical weight loss and recent advances in medical therapeutics are more effective at reducing obesity and obesity-related complications. Obesity in PLWH substantially increases the risk for cardiometabolic complications and poor health outcomes. Surgical and medical weight loss interventions are effective treatments to reduce obesity and obesity-related complications, though further research in PLWH is needed to define optimal management.
Cytotoxic CD4 T cells (CD4 CTL) have long been recognized for their potentially protective role in people with HIV, but only recently have their contributions in HIV-1 pathogenesis and viral persistence been appreciated. This review summarizes evidence highlighting their critical role in HIV-1-mediated CD4 T cell depletion and in maintaining the viral reservoir, with special consideration for their abundance and development in the gut. CD4 CTL are increased in frequency in people with HIV (PWH). Granzyme B activity in CD4 CTL promotes HIV-1 mediated death of gut CD4 T cells. CD4 CTL that express survival markers such as BCL-2, TNFR2/CD120b, and OX40 appear to resist HIV-1 mediated cell death, potentially contributing to the viral reservoir. Multiple cytokine (IL-2, IL-15) and transcriptional (BACH2, EOMES) pathways were implicated in CD4 CTL differentiation and maintenance. In the gut, CD4 CTL activity appears to be intricately linked to the microbiome, as cytotoxic protein expression can develop in response to bacterial exposure. CD4 CTL from the gut, induced by the presence of bacteria in vitro, are highly infectable by HIV-1. CD4 CTL may act as dual agents in HIV-1 infection, amplifying tissue damage and serving as resilient cellular reservoirs. Understanding the mechanisms regulating their differentiation, cytotoxicity, and survival could inform new therapeutic strategies aimed at restoring gut mucosal integrity, resolving chronic inflammation, and targeting the persistent HIV-1 reservoir.
Adolescents and young adults (AYA) face disproportionately worse outcomes along the HIV prevention and care continuum. Despite global commitments to AYA engagement, AYA remain underrepresented in research, programming, and policy development. We summarize recent innovations in AYA engagement within the HIV literature and reflect on the 2023 Blueprint Collaborative, a UNICEF/WHO/UNAIDS initiative where AYA (ages 10–30) shaped global adolescent HIV strategy. Our review found examples of AYA engagement across the intervention life cycle, including in shaping research agendas, designing interventions, and building AYA capacity for sustainability. For the Blueprint Collaborative, which featured a AYA-led evidence synthesis and global open call, we assessed AYA engagement using the RIGHTS framework. A major strength of the Blueprint Collaborative was the robust AYA engagement, moving beyond AYA consultations to AYA leadership. AYA shared decision-making authority with adults as researchers, organizers, and open call judges. Through a “learning by doing” approach, AYA gained skills in research and multidisciplinary collaboration. Blueprint results were presented to senior leadership, developed into strategy, and disseminated through publications and AYA networks. AYA leadership can provide several benefits for AYA research and programming, such as institutionalizing community engagement, improving research relevance, and advancing equity. AYA are eager and capable of driving HIV strategy and policy, but senior partners should step back to enable these opportunities. Senior partners might better serve to support AYA leadership in strategic planning to align programming with AYA priorities and build research and advocacy skills.
Herpes simplex virus type 2 (HSV-2) infection is one of the most prevalent sexually transmitted infections worldwide, with implications for HIV acquisition, transmission, and disease progression. This review synthesizes current evidence and guidance on HSV-2 serologic screening, emphasizing its relevance for HIV prevention and care. International guidelines advise against routine general population-level serologic screening for HSV-2 in asymptomatic persons. Key limitations include poor test specificity, the absence of potent antivirals or therapeutic vaccines, lack of curative therapy, no demonstrated population-level benefit, and psychosocial harms associated with diagnosis. Current practice instead emphasizes diagnostic testing in symptomatic persons and targeted screening in defined contexts—such as among people with HIV in specific clinical situations, sex partners of those with HSV-2 infection, certain pregnant women, persons seeking sexual health care, and persons with recurrent or atypical symptoms—where results may directly inform management. Emerging technologies, including highly specific assays, novel potent antivirals, therapeutic vaccines, and curative strategies, may eventually shift the cost–benefit balance of general screening. Evidence supports targeted rather than general population-level screening to maximize clinical benefit while minimizing harm. New evidence demonstrating that interventions can achieve measurable population-level reductions in disease burden or transmission, together with future advances in diagnostics and therapeutics, may eventually justify integrating routine HSV-2 screening into broader contexts, including into HIV prevention and care.
Asset mapping aims to engage members of a community to explore and map assets that are solutions to social issues such as homelessness or access to health care. The purpose of this scoping review was to determine the scope of asset mapping as an approach to HIV care cascade outcomes, synthesize available evidence on this method’s application in research, and identify opportunities for future interventions and research based in this methodology. This scoping review follows the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for Scoping Reviews checklist. Databases used were: PubMed, CINAHL, EMBASE, and Scopus. Only articles featuring studies targeting the HIV care cascade were included. Our focus was studies that explored, described, or mapped tangible or intangible assets, employed a strengths-based approach, and addressed capacity to develop solutions. Several researchers independently reviewed all abstracts and full text articles. A total of 305 articles were found. After removal of duplicates, 207 articles remained. From the title and abstract review, 189 articles (91
