Current opinion in HIV and AIDS最新文献

Purpose of review: HIV-associated tuberculosis (TB) remains a major driver of morbidity and mortality in children and adolescents younger than 15 years (CLWH). The purpose of this review is to highlight recent findings in the areas of prevention, diagnosis, and treatment of HIV-associated TB in CLWH and to highlight knowledge and implementation gaps.

Recent findings: We found that despite access to antiretroviral therapy (ART), high rates of HIV-associated TB are still reported, and with an unacceptably high mortality. There are no advances in screening for TB, but shorter courses of rifapentine-based TB preventive therapy are becoming available. The use of algorithms in TB diagnosis can potentially simplify the therapeutic decision making. There are more data supporting the use of dolutegravir (DTG) with rifampicin and a need to study unadjusted DTG especially in the youngest children. Short course therapy for nonsevere pulmonary TB is currently implemented and programmatic outcome should be studied in CLWH. Low uptake of ART and poor suppression remains an important driver of HIV-associated TB.

Summary: Although screening and diagnosis remains challenging, there are several advances in the prevention and treatment of HIV-associated TB. Effective implementation of these strategies is needed to advance the outcomes of CLWH.

Purpose of review: Adolescents and youth living with HIV (AYLHIV) have worse outcomes at all stages of the care cascade when compared with adults, yet adolescents and youth with unsuppressed viral load are typically excluded from phase 3 studies of novel HIV therapeutic agents and emerging strategies. Long-acting agents have the potential to radically change outcomes for young people struggling with adherence to daily oral HIV medications.

Recent findings: 1.5 million children aged less than 15 years live with HIV and more than 100 000 acquire HIV perinatally every year. Adolescents and youth aged 10-24 years comprise ∼40% of global incident HIV infections. Rates of viral suppression among AYLHIV vary markedly from 44 to 88%, resulting in morbidity and risks of transmission to partners and infants. Virological failure is mostly due to poor adherence, and AYLHIV express high levels of interest and acceptability of alternatives to oral daily medications, such as long-acting antiretroviral formulations. Emerging data regarding their use in populations with unsuppressed viral load are encouraging.

Summary: AYLHIV, including populations without virologic suppression, must be prioritized for the programmatic implementation and research of long-acting HIV drugs and other therapeutic strategies to prevent morbidity and mortality and to ultimately end the HIV epidemic.

Purpose of review: To analyse the main evidence and recommendations for the management of hepatitis co-infection in children living with HIV.

Recent findings: We analysed available data pertaining to the natural history of liver disease and treatment of co-infected children.

Summary: Viral hepatitis co-infection in people living with HIV (PLHIV) is a global problem owing to the shared routes of transmission, particularly in areas of high endemicity for the three viruses. Viral hepatitis co-infection can accelerate liver disease progression and increase morbidity and mortality, even in patients on suppressive antiretroviral treatment (ART). Viral hepatitis should be routinely screened in PLHIV and, once diagnosed with viral hepatitis, PLHIV should be closely monitored for liver disease progression and complications. Children living with HIV-HBV co-infection should be treated with ART containing agents which are active against both viruses. Children living with HIV-HCV co-infection should receive directly acting antivirals (DAA) to eradicate HCV infection. Prevention measures to reduce vertical and horizontal transmission of HBV and HCV (anti-HBV vaccination and immunoglobulins, anti-HBV treatment in pregnancy, anti-HCV DAAs in people of childbearing age, avoiding blood contact, sexual barrier precautions) should be adopted and encouraged, particularly in high endemicity countries.

Purpose of review: To review the latest data on prevention of HIV vertical transmission in Asia and Africa and discuss strategic directions to achieve an AIDS free generation by 2030.

Recent findings: Progress in vertical transmission elimination efforts in Africa and Asia have stalled in the last decade, with 130 000 new infections in 2022. Main causes of vertical transmissions vary; in Asia-Pacific due to its low-burden, thus low testing coverage, but high overall vertical transmission rates, in South and East Africa due to new HIV infections during pregnancy and breast/chestfeeding, whereas in Western and Central Africa due to low antiretroviral therapy (ART) coverage. Long-acting injectable ART and neutralizing antibodies for treatment and prevention show promise in supporting efforts to further reduce vertical transmissions. Integrated and more accessible pre- and postnatal care is needed to achieve an AIDS-free generation.

Summary: Much can be implemented to address existing HIV service gaps; including strengthening of HIV prevention services for youth and women of childbearing age and pregnant people, early detection and treatment, and the delivery of integrated services that can reach and retain pregnant and postpartum people living with HIV in care.

Purpose of review: Universal antiretroviral (ART) coverage and virological suppression are fundamental to ending AIDS in children by 2030. Availability of new paediatric dolutegravir (DTG)-based ART formulations is a major breakthrough and will undoubtedly help achieve this goal, but treatment challenges still remain.

Recent findings: Paediatric formulations remain limited compared to those for adults, especially for young children, those unable to tolerate DTG or with DTG-based first-line ART failure. Tenofovir alafenamide is virologically superior to standard-of-care backbone drugs in second-line, but paediatric formulations are not widely available. The roles of resistance testing and recycling of backbone drugs following first-line ART failure remain to be determined. Results of trials of novel treatment strategies including dual therapy and long-acting agents are awaited. Although numbers are currently small, safe and effective ART options are urgently required for children developing DTG resistance.

Summary: The antiretroviral treatment gap between adults and children persists. The potential benefits from rollout of new paediatric DTG-based fixed-dose combination ART for first-line treatment are considerable. However, children remain disadvantaged when DTG-based first-line ART fails or cannot be used. Research efforts to address this inequity require prioritisation in order to ensure health outcomes are optimised for all ages in all settings.

Purpose of review: Durable HIV-1 remission has been reported in a person who received allogeneic stem cell transplants (SCTs) involving CCR5 Δ32/Δ32 donor cells. Much of the reduction in HIV-1 burden following allogeneic SCT with or without donor cells inherently resistant to HIV-1 infection is likely due to cytotoxic graft-versus-host effects on residual recipient immune cells. Nonetheless, there has been growing momentum to develop and implement stem cell therapies that lead to durable long-term antiretroviral therapy (ART)-free remission without the need for SCT.

Recent findings: Most current research leverages gene editing techniques to modify hematopoietic stem cells which differentiate into immune cells capable of harboring HIV-1. Approaches include targeting genes that encode HIV-1 co-receptors using Zinc Finger Nucleases (ZFN) or CRISPR-Cas-9 to render a pool of adult or progenitor cells resistant to de-novo infection. Other strategies involve harnessing multipotent mesenchymal stromal cells to foster immune environments that can more efficiently recognize and target HIV-1 while promoting tissue homeostasis.

Summary: Many of these strategies are currently in a state of infancy or adolescence; nonetheless, promising preclinical and first-in-human studies have been performed, providing further rationale to focus resources on stem cell therapies.

Purpose of review: HIV-1 infection contributes substantially to global morbidity and mortality, with no immediate promise of an effective prophylactic vaccine. Combination antiretroviral therapy (ART) suppresses HIV replication, but latent viral reservoirs allow the virus to persist and reignite active replication if ART is discontinued. Moreover, inflammation and immune disfunction persist despite ART-mediated suppression of HIV. Immune checkpoint molecules facilitate immune dysregulation and viral persistence. However, their therapeutic modulation may offer an avenue to enhance viral immune control for patients living with HIV-1 (PLWH).

Recent findings: The success of immune checkpoint inhibitor (ICI) therapy in oncology suggests that targeting these same immune pathways might be an effective therapeutic approach for treating PLWH. Several ICIs have been evaluated for their ability to reinvigorate exhausted T cells, and possibly reverse HIV latency, in both preclinical and clinical HIV-1 studies.

Summary: Although there are very encouraging findings showing enhanced CD8 + T-cell function with ICI therapy in HIV infection, it remains uncertain whether ICIs alone could demonstrably impact the HIV reservoir. Moreover, safety concerns and significant clinical adverse events present a hurdle to the development of ICI approaches. This review provides an update on the current knowledge regarding the development of ICIs for the remission of HIV-1 in PWH. We detail recent findings from simian immunodeficiency virus (SIV)-infected rhesus macaque models, clinical trials in PLWH, and the role of soluble immune checkpoint molecules in HIV pathogenesis.

Purpose of review: The 'PrEP cliff' phenomenon poses a critical challenge in global HIV PrEP implementation, marked by significant dropouts across the entire PrEP care continuum. This article reviews new strategies to address 'PrEP cliff'.

Recent findings: Canadian clinicians have developed a service delivery model that offers presumptive PEP to patients in need and transits eligible PEP users to PrEP. Early findings are promising. This service model not only establishes a safety net for those who were not protected by PrEP, but it also leverages the immediate salience and perceived benefits of PEP as a natural nudge towards PrEP use. Aligning with Behavioral Economics, specifically the Salience Theory, this strategy holds potential in tackling PrEP implementation challenges.

Summary: A natural pathway between PEP and PrEP has been widely observed. The Canadian service model exemplifies an innovative strategy that leverages this organic pathway and enhances the utility of both PEP and PrEP services. We offer theoretical insights into the reasons behind these PEP-PrEP transitions and evolve the Canadian model into a cohesive framework for implementation.