Current opinion in HIV and AIDS最新文献

Purpose of review: To describe the current research on geriatric syndromes in women with HIV (WWH) and their potential clinical implications.

Recent findings: Geriatric syndromes are multifactorial age-related changes that are associated with functional decline. In those without HIV, many geriatric syndromes have a higher prevalence in women. In those with HIV, there are important sex differences in frailty trajectories and sarcopenia. WWH demonstrate an increased risk for osteoporosis and cognitive decline compared to men and to women without HIV. Urinary incontinence and social isolation are also prevalent in WWH and impact quality of life. Several of these geriatric syndromes are modified by the menopausal transition in WWH.

Summary: Research is needed to identify the predictors of geriatric syndrome development and progression in WWH. These findings could inform timing of screening or intervention strategies for aging WWH.

Purpose of review: Recent findings on the critical pathogenic role of inflammatory pDC and type 1 interferons (IFN-I) in HIV-1 pathogenesis in humanized mice and its correlation with inflammatory diseases in people living with HIV-1 (PLWH) suggest that targeting the pDC/IFN-I signaling pathway will reverse HIV-induced inflammation to treat HIV-associated end-organ diseases and rescue anti-HIV immunity to reduce or control HIV-1 reservoirs.

Recent findings: In both humanized mice and in PBMC from people living with HIV-1 (PLWH), depletion of pDC or inhibition of IFN-I signaling resolves IFN-associated inflammation, rescues anti-HIV T cell functions and reduces HIV-1 reservoir cells. In humanized mice with HIV-1 persistent infection under effective HAART, persistent pDC activation and IFN-I signaling has been shown to induce HIV-associated tissue injury and anti-HIV T cell impairment. in HIV-infected mice with effective HAART, pDC depletion phenocopies what is achieved with blocking IFN-I signaling in reversing HIV-induced inflammation, rescuing anti-HIV T cells and reducing HIV-1 reservoirs. Interestingly, in both humanized mice and in PBMC from PLWH, depletion of pDC or inhibition of IFN-I signaling rescues anti-HIV TCF1+ (T cell factor 1) PD1+ (programmed cell death protein 1) CD8 T cell functions to enhance the effect of PD1 immune checkpoint inhibitor (ICI) to reduce HIV-1 reservoir cells.

Summary: These findings functionally define the role of the pDC/IFN-I pathway in HIV-associated inflammation, HIV-1 reservoir persistence and end-organ diseases, and suggest that inhibiting pDC or blocking IFN-I signaling will provide a novel therapeutic strategy to reverse inflammation-associated diseases and to rescue anti-HIV immunity that cooperates with PD1 ICI effect to reduce or control HIV-1 reservoirs.

Purpose of review: To summarize the relationship of vaginal and gut microbiomes with HIV transmission, pathogenesis, and treatment, focusing on women's health.

Recent findings: Bacterial vaginosis (i.e., vaginal microbiome dysbiosis) is a well established risk factor for HIV acquisition, and recent research focused on molecular mechanisms and biomarkers for HIV acquisition related to vaginal microbiota. Recent clinical trials reported on probiotics to treat bacterial vaginosis with the goal of HIV prevention; however, durability of treatment response remains sub-optimal. The vaginal microbiome may impact efficacy of preexposure prophylaxis (PrEP) and antiretroviral therapy (ART) in vaginal tissue, with recent literature examining vaginal microbiota and long-acting PrEP vaginal rings. Some research also suggests effects of PrEP or ART initiation on the vaginal microbiome. Regarding the gut microbiome, associations with HIV status may differ more by sexual practices than biological sex, and sex-specific roles of gut microbiota in HIV pathogenesis and treatment are unknown. Interactions of the gut microbiome with estrogens could underlie a role of gut microbiota in health of women with HIV.

Summary: The vaginal microbiome remains an important factor in HIV acquisition, prevention, and treatment in women. The gut microbiome has roles in HIV pathogenesis and treatment, but women-specific effects are unclear.

Purpose of review: To summarize women-specific contributors to cardiovascular disease (CVD) in women with HIV (WWH) and translate recent evidence on imaging, biomarkers, and prevention into practical strategies for assessment and management.

Recent findings: WWH experience higher rates of adverse pregnancy outcomes and cardiometabolic complications. Weight gain associated with some integrase inhibitors may compound postpartum risk. Early menopause is more common, and biochemical confirmation improves attribution of symptoms and risk. Subclinical myocardial injury is frequent; coronary microvascular dysfunction and cardiac magnetic resonance markers of fibro-inflammation appear even with viral suppression. Traditional calculators often underpredict CVD events. Novel tools, including triglyceride-glucose trajectories, and imaging-linked scores, show promise for earlier detection. The REPRIEVE trial demonstrated efficacy of primary prevention statins for people with HIV across sexes, yet women remain less likely to receive statins.

Summary: Care requires integration of sex-specific risk enhancers, trauma-informed approaches, and proactive cardiovascular surveillance. Consideration for annual risk assessment incorporating HIV-related immune and metabolic factors, early statin initiation when 10-year risk is ≥5% or enhancers are present, selective advanced imaging in advanced immunosuppression, and use of accessible biomarkers such as the triglyceride-glucose index. Priorities include validation of women-specific prediction tools and closing implementation gaps.

Purpose of review: Chronic liver disease is the leading cause of non-HIV-related mortality in women with HIV (WWH). We review the pathophysiology of liver injury in WWH, natural history and management of common liver diseases, and role of viral, pharmacologic, and sex hormone-related factors in exacerbating liver disease progression in WWH.

Recent findings: In the current era of effective antiretroviral therapy (ART), viral hepatitis related liver disease has decreased in prevalence, while alcohol-associated and metabolic dysfunction associated steatotic liver disease (MASLD) have become more common. Several mechanisms cause accelerated fibrogenesis in WWH, including direct cytopathic effects from HIV, ART, gastrointestinal barrier impairments, and microbiome alterations. The menopausal transition is a critical period in which WWH develop a profibrogenic state exacerbated by HIV-associated estrogen deficiency. Glucagon-like peptide-1 use in WWH holds promise in reversing hepatic steatosis. Higher rates of hazardous alcohol use and psychiatric comorbidities in WWH, compared to men with HIV, increases the risk of alcohol and viral hepatitis related liver disease.

Summary: WWH experience unique challenges to achieving optimal liver disease care due to social marginalization, biological sex differences, and HIV infection itself. Future research investigating mechanisms and potential interventions is needed to improve liver health outcomes in this high-risk population.

Purpose of review: Although current antiretroviral therapy effectively suppresses HIV-1 replication, it does not eliminate infected cells. The virus persists in a latent form within long-lived reservoir cells, leading to viral rebound after treatment interruption. Developing novel therapeutic strategies capable of targeting and eliminating these persistent reservoirs remains a major obstacle to achieving a cure. This review explores the emerging role of CD4 mimetic compounds (CD4mc) in enhancing nonneutralizing antibody (nnAb)-based HIV-1 immunotherapies.

Recent findings: We review recent advances in the development of distinct families of CD4mc, focusing on their ability to prevent viral entry, sensitize HIV-1 virions and infected cells to nnAb-mediated immune responses, and block the immunomodulatory activities of soluble gp120. We also discuss the design of nnAb-CD4mc cocktails and fusion molecules, and the evidences supporting their in vitro and in vivo efficacy.

Summary: CD4mc exhibit multifunctional activities that enhance nnAb-based HIV-1 immunotherapies. They represent a promising component of future strategies aimed at eliminating the HIV-1 reservoir.

Purpose of review: Women with HIV (WWH) face unique gynecologic and reproductive health challenges related to HIV infection itself, antiretroviral therapy (ART) and medication-interactions with ART.

Recent findings: WWH experience higher incidence of co-infection with many sexually transmitted infections (STIs), including hepatitis and human papilloma virus (HPV)-related dysplasia and cancers. Regular preventive care and vaccination are key. WWH additionally experience higher rates of unplanned pregnancy than the general population, with a high unmet need for contraception. For WWH in mixed-status relationships who desire conception, there is a shift towards preexposure prophylaxis and treatment as prevention, and away from older assisted reproductive interventions, such as sperm washing. ART is well tolerated and critically important in both pregnancy and breastfeeding, for both maternal health and prevention of perinatal transmission. Given the emergence of increased safety data for breastfeeding in the setting of perinatal and postpartum transmission, the United States guidelines have shifted to recommend shared decision making around infant feeding.

Summary: Recommendations to optimize gynecologic and reproductive healthcare for WWH include patient centered counseling, shared decision making, and access to the full spectrum of treatment and prevention options, integrated into HIV care.

Purpose of review: As more women with HIV survive into older age, the menopausal transition has emerged as a critical yet underexplored determinant in HIV pathogenesis. Declining exposure to estrogens during menopause alters innate and adaptive immunity, driving inflammation, comorbidities, and viral persistence.

Recent findings: Estrogen influences both innate and adaptive immune responses. Estradiol enhances plasmacytoid dendritic cell type I interferon (IFN) production through Toll-like Receptor 7 (TLR7), promotes natural killer (NK) cell activity, and tempers monocyte/macrophage activation. Menopause reverses these effects, contributing to elevated inflammatory mediators. On the adaptive side, estrogen loss increases T-cell activation and exhaustion, impairs B-cell responses, and removes estrogen receptor (ER)-mediated suppression of HIV transcription. Together, these shifts may promote stabilization or expansion of the HIV reservoir in perimenopausal women with HIV, in contrast to the gradual decay often observed in men on antiretroviral therapy (ART).

Summary: Estrogen depletion during menopause reshapes immunity in women with HIV, fueling chronic inflammation, comorbidity risk, and HIV reservoir persistence. Integrating reproductive aging into HIV cure and comorbidity research, and testing hormone-based and anti-inflammatory interventions, will be essential to improve health outcomes for aging women with HIV.

Purpose of review: HIV infects a broad array of tissues throughout the body. Consequently, any successful HIV cure strategy will need to target tissue HIV reservoirs, in addition to peripheral blood. Here we review recent immunotherapy approaches for HIV cure, with a focus on their ability to target viral tissue reservoirs, including immune privileged sites like the central nervous system (CNS).

Recent findings: Recent clinical trials of immunotherapy for HIV cure have demonstrated viral control in a subset of participants. T cell therapies, especially chimeric antigen receptor (CAR) T cells that can be targeted to lymphoid tissue, are highly promising, as are monoclonal antibody therapies such as broadly neutralizing antibodies to suppress HIV viremia and immune checkpoint inhibitors to enhance immune function. Despite this success, the penetration of many of these agents into the CNS is limited, and this remains a barrier to more widespread success of these therapies.

Summary: Immunotherapies represent a promising path toward an HIV cure, however their ability to target viral reservoirs within tissues represents a major challenge. Combination approaches leveraging multiple immunotherapy strategies, and other agents to reduce the HIV reservoir will likely be required to achieve viral control in the absence of antiretroviral therapy.