Current Opinion in HIV and AIDS最新文献

Purpose of review: Tenofovir-based oral PrEP has been effective in reducing population-level HIV incidence in multiple settings, although disparities remain. Injectable cabotegravir-based PrEP is an alternative that may be attractive to individuals with adherence challenges or who do not desire to take a daily medication. We review promises and challenges of cabotegravir-based PrEP.

Recent findings: Cabotegravir has demonstrated higher effectiveness than oral PrEP in two randomized trials, with a hazard ratio of 0.31 for HIV incidence among MSM and transgender women across multiple settings [95% confidence interval (CI) 0.18-0.62] and 0.11 for cisgender women in sub-Saharan Africa (95% CI 0.040.32). Cabotegravir was also highly effective among populations with disproportionate HIV incidence. Although cabotegravir breakthrough was rare, diagnosis was delayed with use of antigen/antibody-based HIV tests, and resistance occurred with breakthrough infections. Implementation will need to overcome several challenges, including HIV RNA laboratory monitoring not being widely available, requirement for additional staff time and clinic space, and need to provide oral medication during interruptions in dosing.

Summary: Cabotegravir-based PrEP is a highly effective additional PrEP option that will expand HIV prevention options. For successful roll-out, strategies for streamlined and accessible delivery of cabotegravir in real-world settings will need to be developed.

Purpose of review: HIV preexposure prophylaxis (PrEP) is a key tool in ending the HIV epidemic. Long-acting cabotegravir (LA- CAB) phase II/III studies revealed promising efficacy in preventing HIV acquisition. Here, we discuss key considerations for implementing LA-CAB in low- and middle-income countries (LMIC).

Recent findings: PrEP roll out in LMIC is still far from ideal, and contextual factors within LMIC vary widely. Implementation science studies are urgently needed to optimize the implementation of LA-CAB in different settings, consider effective service delivery models, and ensure program sustainability. Preferences and concerns regarding LA-CAB among potential users are unknown but likely specific to local context. Demedicalized and simplified PrEP service delivery increases uptake, and ways to safely and effectively do the same for LA- CAB need to be explored. Although ideally LA-CAB should be an additional choice of HIV prevention method, its cost will be the major determinant in deciding its position as a first line choice or restricted second-line option.

Summary: LA-CAB has the potential to enhance PrEP uptake. However, several implementation challenges need to be explored and addressed to ensure it can be accessed and utilized in different settings by those who need it the most.

Purpose of review: With oral antiretroviral therapy, HIV has become a manageable chronic illness. However, UNAIDS targets for virologic suppression have not yet been attained in many low-income and middle-income countries (LMICs). Long-acting drug formulations hold promise to improve treatment outcomes. In this rapidly evolving area of research, we aim to review recent literature on the treatment of HIV with long-acting agents and identify implementation considerations for LMICs.

Recent findings: Randomized controlled trials have shown that monthly long-acting injectable cabotegravir (CAB) and rilpivirine (RPV) is noninferior to oral ART, and 2-monthly CAB/RPV is noninferior to monthly injections. However, few people from LMICs were included. A modelling study predicts that in sub-Saharan Africa, injectable CAB/RPV is best targeted to those with poor adherence (HIV viral load >1000 copies/ml) in whom cost-effectiveness is greatest and risk of contributing to further resistance is no greater than continuation of oral ART. Other promising agents, such as lenacapavir are under investigation and may prove particularly useful in heavily treatment-experienced adults.

Summary: Long-acting regimens are a promising advance in HIV treatment. By extending the dosing interval, increasing convenience and being discreet these regimens may reduce HIV treatment challenges. However, there are multiple implementation considerations in LMICs including the need for exclusion of hepatitis B, cold chain, oral bridging in case of missed dosing and switching during tuberculosis therapy. Efficacy and safety data are also awaited for settings without routine access to baseline resistance testing or regular viral load monitoring and for special populations, such as pregnancy, children and the elderly.

Purpose of review: Broadly neutralizing antibodies (bNAbs) are a potential new therapeutic strategy to treat HIV infection. This review explores possible mechanisms of action of bNAbs and summarizes the current evidence supporting their immunomodulatory properties, which might lead to sustained virological remission - the 'vaccinal effect'.

Recent findings: Antiretroviral therapy (ART) is required to confer lasting HIV suppression; stopping ART almost invariably leads to HIV recrudescence from a persistent pool of virally infected cells - the HIV reservoir. HIV-specific broadly neutralizing antibodies (bNAbs) may confer viral control after ART cessation predominantly through blockade of viral entry into uninfected target cells. In some human and animal studies, HIV bNAbs also conferred lasting viral suppression after therapeutic bNAb plasma levels had declined. Immune-modulatory mechanisms have been postulated to underlie this observation - the 'vaccinal effect'. Hypothesized mechanisms include the formation of immune complexes between bNAbs and HIV envelope protein, thereby enhancing antigen presentation and uptake by immune cells, with boosted adaptive immune responses subsequently controlling the HIV reservoir.

Summary: There is emerging evidence for potent antiviral efficacy of bNAb therapy. Whether bNAbs can induce sustained viral suppression after dropping below therapeutic levels remains controversial. Mechanistic data from on-going and future clinical trials will help answer these questions.

Purpose of review: Key populations are disproportionately affected by human immunodeficiency virus (HIV). Access, retention, and adherence are important barriers for the efficacy of preexposure prophylaxis (PrEP) and HIV treatment among these populations. Long-acting (LA) antiretrovirals hold the promise to solve some of these backdrops. The objective of the current review is to update the perceptions of key populations and PLWH about LA, based on their opinion, acceptability, and willingness to use it.

Recent findings: According to the review preferences for LA vary with the population studied. Regarding people living with HIV (PLWH), male having sex with men are interested in having different options, adolescents are interested in LA (strong preference for implants), yet also perceive substantial obstacles to using biomedical prevention; transgender women aimed to nonvisible small implants, with long-lasting effects or LA injections that can be applied in other areas than buttocks, and women who experienced history of medical injections might increase preference for LA (except for history of people who inject drugs [IDU]). Female sex workers and IDU both showed interest in LA-PrEP. Regarding antiretroviral therapy, LA increased treatment satisfaction and acceptance, mainly among those receiving injections every 2 months. LA helped overcome pill fatigue, stigma, and adherence issues.

Summary: Knowing preferences for biomedical interventions will contribute to better understanding and developing effective strategies for these populations.

Purpose of review: The purpose of this review is to identify themes across articles that aimed to explore HIV-related syndemics in 2020 and 2021 and to discuss their implications for research on syndemics.

Recent findings: We identified 189 articles on syndemics between 2020 and 2021. Key themes across studies included COVID-19; mental health and psychosocial challenges; substance use; socio-structural factors; protective factors; and methodological approaches. COVID-19's implications for HIV syndemic research were discussed. Mental health and substance use research largely examined linkages with sexual practices or reduced HIV care retention. Researchers examined associations between socio-structural variables (e.g. poverty) and elevated HIV exposure, reduced HIV testing and poorer health. Concepts of water insecurity and 'ecosyndemics' were also raised, as was the importance of attending to noncommunicable diseases and comorbidities. Most studies did not assess interactions between health conditions, signalling the need for methodological grounding in the foundational concepts of syndemic theory.

Summary: Most studies recommended that HIV prevention and care research attend to the interplay between poor mental health, substance use and multidimensional violence. Increased attention to structural factors, particularly exacerbated poverty in the COVID-19 pandemic, is required. Research can identify protective factors to harness to advance HIV prevention and care.