Current opinion in HIV and AIDS最新文献

Purpose of review: Direct-acting antivirals (DAAs) have transformed hepatitis C virus (HCV) management. People with HIV (PWH) are prioritized in elimination strategies due to higher HCV prevalence, faster progression, and linkage to HIV care. This review summarizes evidence on HCV elimination in PWH, highlighting progress, gaps, and future directions toward WHO elimination targets.

Recent findings: DAAs achieve cure rates above 95% in PWH across stages and contexts, with pangenotypic regimens enabling integration into HIV services. Studies in high-income countries report steep declines in HCV viremia among PWH, some nearing microelimination. Yet gaps persist as subsets remain untreated, with lower uptake among women, heterosexual men, migrants, and people who inject drugs (PWID). Reinfections cluster among MSM and PWID, though overall incidence has declined with treatment-as-prevention. In contrast, low-income and middle-income countries face restricted access, high costs, limited harm reduction, stigma, and criminalization, leaving interim 2025 goals unmet. Integrated HIV-HCV-substance use care, point-of-care diagnostics, telehealth, and community outreach improve linkage and treatment completion.

Summary: HCV elimination among PWH is feasible in well resourced settings, but global progress remains uneven. Universal screening, unrestricted DAA access, harm reduction, and sustained political commitment are essential to consolidate gains and prevent setbacks.

Purpose of review: In the European region of the WHO, the largest part of tuberculosis (TB)/HIV co-infection is found in parts of Eastern Europe. In other parts of Europe, TB among people with HIV has been declining with migrants at highest risk. This review provides an overview of the epidemiology, determinants, regional differences, diagnostic and therapeutic standards, and future challenges of TB/HIV co-infection in Europe.

Recent findings: Socioeconomic factors, including substance abuse, incarceration and migration as well as persistent gaps in early HIV and TB diagnosis, and lack of antiretroviral therapy (ART) continue to drive TB incidence and poor outcomes; meanwhile, new shorter (all-oral) TB regimens and diagnostic innovations offer major advances, but their impact is uncertain due to unequal access and emerging drug resistance.

Summary: Addressing TB/HIV co-infection in the WHO European region requires scaling up early HIV and TB testing, and ART coverage; integration of HIV, TB, and substance-use services within person-centered care models; strengthening laboratory and surveillance systems in Eastern Europe and Central Asia; and addressing social determinants-such as poverty, stigma, and substance use disorders-that drive much of the TB/HIV burden in the region.

Purpose of review: To summarize recent advances in drug-resistant tuberculosis (DR-TB) treatment for people with HIV (PWH), including drug-drug interactions, investigational medications and host-directed therapy, as well as emerging evidence on novel treatment regimens, post-TB complications, and DR-TB medication resistance among PWH.

Recent findings: Treatment for DR-TB has evolved to shorter, all-oral regimens with reduced drug-drug interactions. However, emerging dolutegravir resistance may necessitate protease inhibitor-based ART regimens resulting in interactions that complicate DR-TB management. Investigational TB medications including BTZ-043, sutezolid, and delpazolid demonstrate promising bactericidal activity in early phase trials. Several clinical trials have demonstrated the efficacy of 6-9 month DR-TB regimens and have included PWH; however, all successful shortened regimens currently contain bedaquiline, which limits options for PWH in areas with emerging bedaquiline resistance. While treatments targeting Mycobacterium tuberculosis are the mainstay of treatment, host-directed therapy is being evaluated both as an intervention for treatment and for the prevention of immune reconstitution inflammatory syndrome and post-tuberculosis lung disease.

Summary: Treatment options for DR-TB have improved dramatically with less toxic, more effective regimens, but managing HIV-associated DR-TB continues to require careful attention to drug-drug interactions and HIV related co-morbidities. Research into novel DR-TB regimens, especially for people with bedaquiline resistance, and host-directed therapies are critical to realize continued improvement in HIV-associated DR-TB outcomes.

Purpose of review: This review describes the drastic changes in the epidemiology, treatment and prevention landscape of hepatitis D virus (HDV), one of the more severe forms of viral hepatitis, that have occurred over the last decade in the context of HIV and hepatitis B virus (HBV).

Recent findings: HBV/HDV infection appears mostly concentrated within specific groups where the HIV-epidemic is localized and more general where HIV is endemic; nevertheless, epidemiological data are lacking, especially for individuals currently in care. New treatments bearing anti-HDV activity have been or are currently being developed. Meanwhile, HBV vaccines with a novel CpG-adjuvant have produced higher rates of vaccination response.

Summary: Recent European guidance recommends that all individuals with HBV, regardless of HIV-status, undergo anti-HDV antibody testing. HDV testing must clearly be increased, which could be aided by reflex HBV/HDV testing. Individuals with active infection should be considered for treatment and close monitoring. Of all novel anti-HDV agents, only bulevirtide has been evaluated in HIV/HBV/HDV infection and extended treatment durations are possible to increase response rates. Newer vaccinations should be used for those without HBV vaccination, especially when no longer using tenofovir-containing regimens, to prevent both HBV/HDV infection.

Purpose of review: mpox vaccination remains the only effective drug-based tool against mpox. Currently, there are two third-generation vaccines: LC16m8 and MVA-BN. Immunogenicity, observational and modelling data have demonstrated their efficacy in preventing mpox. However, evidence of waning immunity from 1 year after mpox vaccination has emerged, while mpox is still circulating worldwide, and there is a threat of a more contagious and virulent clade.

Recent findings: We review the available data on immunogenicity of mpox vaccines, after primary and booster dose. There are pros and cons to recommending a booster dose. Immunogenicity data showed that an MVA-BN booster can effectively induce a humoral response, which is important for protective immunity. However, without a validated correlate of protection, clinical data are needed, and public policy considerations such as the limited numbers of doses available must be taken into account.

Summary: Implementing a booster dose in guidelines requires a careful consideration of dose allocation globally, a better characterization of the burden of mpox, and clinical data on vaccine effectiveness to define vaccination objectives.

Purpose of review: The 2022 global Mpox outbreak was characterised by prominent cutaneous and mucocutaneous findings, often with significant associated pain, that posed unique challenges for clinicians. To date, there are no known effective treatments that reduce time to lesion resolution.

Recent findings: Although clade IIb Mpox is generally milder than endemic forms, this outbreak was notable for localized lesions to head, genital or perianal skin as a result of direct inoculation, often with co-infection of other sexually transmitted infections. Bacterial superinfection is among the most common complications of Mpox infection, and can increase the risk of long-term scarring. Complications and more severe illness are more frequent in patients with advanced HIV and low CD4+ T cell count.

Summary: Excellent supportive care for the diverse cutaneous lesions of Mpox is critical to reduce the risk of complications and long-term sequelae of infection. The identification of therapeutics that lead to rapid lesion resolution and reduce local pain and inflammation associated with infection could further improve outcomes.

Purpose of review: Spontaneous control of HIV replication has been primarily associated with cellular immune responses. However, it remains multifactorial, and viral determinants, innate and humoral immune responses could be additional relevant contributors. Furthermore, posttreatment control cases reveal new roles for humoral responses. This review describes the direct, indirect and passive roles of humoral responses in HIV control.

Recent findings: New evidence supports the role of the humoral responses in the natural control of HIV. Indeed, a strong association has been reported between polyfunctional humoral responses and slow disease progression, highlighting the active role of both neutralizing and nonneutralizing antibodies in natural control. Moreover, broadly neutralizing antibodies (bNAbs) are being considered as therapeutic interventions to directly or indirectly mediate HIV control in cure strategies. Data from the latest clinical trials show that treatment with bNAbs may induce high-quality CD8 T-cell responses, pointing to bNAbs as a major indirect strategy to induce durable HIV control. Finally, humoral responses can serve as biomarkers for monitoring elite controllers and have been useful to identify stable aviremic controllers, providing new clinical monitoring tools.

Summary: Humoral responses are relevant for understanding immune mechanisms of control, for defining therapeutic interventions and for the clinical follow-up of elite controllers.

Purpose: Studies in spontaneous controllers of HIV and, more recently, post-treatment controllers have shown that effective HIV-specific CD8+ T cell responses may mediate control of the virus in the absence of antiretroviral therapy. The purpose of this review is to first discuss the unique features of HIV-specific CD8+ T cells in spontaneous controllers. We will then explore how qualities of these cells might be harnessed using T cell engineering strategies.

Summary of recent findings: Several recent studies have deepened our understanding of HIV-specific CD8+ T cell responses in spontaneous controllers. These have included studies elucidating mechanisms by which preferential antigen restriction, specificity, sensitivity, and breadth promote enhanced T cell responses in spontaneous controllers, as well as studies demonstrating that manipulating the differentiation state or localization of HIV-specific T cells might alter their ability to control the virus. In parallel, many recently-developed approaches to engineer anti-cancer T cells could be used to recapitulate key properties of HIV-specific CD8+ T cells from spontaneous controllers (e.g., sensitive antigen receptors, targeted recognition of evolutionarily conserved and/or mutationally constrained epitopes, T cell stem/memory-like functional capacity).

Summary: We identify several opportunities to apply novel approaches being developed in immuno-oncology to enhance the function of engineered T cells for HIV.

Purpose of review: Two-drug regimens (2DR) for antiretroviral therapy are increasingly being recommended for people living with HIV to reduce pill burden and reduce short and long-term toxicity. The exclusion of tenofovir and lamivudine or emtricitabine has implications for acquisition of and reactivation of hepatitis B.

Recent findings: A number of case-series, cohort studies and randomized-controlled trials of 2Drs have reported on the risk of HBV acquisition and HBV-reactivation (HBVr). The risk of HBVr appears negligible in those switching to 2DRs containing lamivudine, and overall low (~1%) in those switching to tenofovir and lamivudine/emtricitabine-free therapy. Even remote HBsAg positivity is associated with a significant risk of HBVr.

Summary: For people with HIV switching to 2DRs careful attention needs to be paid to preswitch HBV serological patterns. For those without previous exposure, and absence of HBsAb, vaccination is important. The risk of HBVr of switching to lamivudine-containing regimens is negligible, and low without tenofovir and lamivudine/emtricitabine. Careful monitoring and preswitch counselling is advised.

Purpose of review: Women with HIV (WWH) face worse HIV care continuum outcomes than men with HIV due to factors such as delayed diagnosis, limited access to care, and increased risk for comorbidities, all of which are exacerbated by social determinants of health and substance use. We reviewed currently available research on substance use and intersecting issues among WWH, with a concentration on how multilevel factors influence women's health. We end with a call to expand research and develop tailored interventions for WWH who use substances.

Recent findings: HIV care continuum outcomes among WWH did not meaningfully improve between 2015 and 2019. Among multiple factors, research suggests that social determinants of health and substance use are key contributors. Substance use, particularly stimulant use, consistently predicts poor HIV outcomes. Very few interventions have been developed to support WWH who use substances. However, existing evidence suggests that interventions designed specifically for women, and which integrate HIV, substance use treatment, and harm reduction services, would help improve outcomes.

Summary: There is a critical need to develop and test integrated care interventions that address the needs of WWH who use substances. Successful interventions could improve individual health and support Ending the HIV Epidemic goals.