Current opinion in HIV and AIDS最新文献

Purpose of review: There is growing consensus that eliciting CD8 + T cells in addition to antibodies may be required for an effective HIV vaccine for both prevention and cure. Here, we review key qualities of vaccine-elicited CD8 + T cells as well as major CD8 + T cell-based delivery platforms used in recent HIV vaccine clinical trials.

Recent findings: Much progress has been made in improving HIV immunogen design and delivery platforms to optimize CD8 + T cell responses. With regards to viral vectors, recent trials have tested newer chimp and human adenovirus vectors as well as a CMV vector. DNA vaccine immunogenicity has been increased by delivering the vaccines by electroporation and together with adjuvants as well as administering them as part of a heterologous regimen. In preclinical models, self-amplifying RNA vaccines can generate durable tissue-based CD8 + T cells. While it may be beneficial for HIV vaccines to recapitulate the functional and phenotypic features of HIV-specific CD8 + T cells isolated from elite controllers, most of these features are not routinely measured in HIV vaccine clinical trials.

Summary: Identifying a vaccine capable of generating durable T cell responses that target mutationally vulnerable epitopes and that can rapidly intercept infecting or rebounding virus remains a challenge for HIV. Comprehensive assessment of HIV vaccine-elicited CD8 + T cells, as well as comparisons between different vaccine platforms, will be critical to advance our understanding of how to design better CD8 + T cell-based vaccines for HIV.

Purpose of review: Ending the HIV epidemic will require the development of additional effective immune-mediated and nonimmune-mediated means of HIV prevention. Evaluating novel interventions requires large, controlled trials demonstrating efficacy. Recent advances in the field of HIV prevention necessitate new approaches to efficacy trial design.

Recent findings: Three classes of efficacy trial designs are possible: standard of prevention-controlled trials, active-controlled trials, and active-controlled trials augmented with external control data. Recent experience with these approaches provides lessons on considerations around and success of the designs. Additional experience and development is needed for the augmented active-controlled trial design.

Summary: Efficacy trials of new HIV prevention interventions are feasible but require careful consideration, given the complexity and dynamic state of the prevention field. While standard of prevention-controlled efficacy trials are reasonable approaches for HIV vaccine and monoclonal antibody efficacy trials, trials of new antiretroviral agents may require active-controlled designs.

Purpose of review: Several anti-HIV-1 broadly neutralizing antibodies (bNAbs) with exceptional breadth and potency, and targeting different HIV-1 envelope epitopes have entered clinical trials. bNAbs are being evaluated for their potential as long-acting alternatives to antiretrovirals in HIV-1 prevention and therapy, and for potential role in strategies aiming at long-term viral remission. Here, we discuss recent findings from bNAb clinical studies.

Recent findings: bNAbs targeting distinct HIV-1 envelope epitopes have shown, in general, favorable safety profiles, and engineered bNAb variants have demonstrated improved pharmacokinetics. Single bNAb infusions transiently decreased viremia with subsequent selection of escape variants, while a combination of two bNAbs successfully maintained viral suppression in individuals harboring antibody-sensitive viruses after antiretroviral therapy (ART) was discontinued. Studies in animal models suggest that bNAbs can modulate immune responses and potentially interfere with the establishment or composition of the latent reservoir, and ongoing clinical studies aim to assess potential bNAb-mediated effects on HIV-1 persistence and host immune responses.

Summary: Early clinical studies support additional evaluation of bNAbs. Antibodies may offer advantages over standard ART for HIV-1 prevention and therapy, and as components of immunologic strategies to achieve sustained virologic control. The evaluation of engineered bNAbs with multispecificity, extended half-lives and increased potency, as well as alternative bNAb-delivery systems are being pursued.

Purpose of review: There is an urgent need to understand new population-level approaches that achieve high levels of treatment and viral suppression for persons living with HIV.

Recent findings: The SEARCH Universal test and treat (UTT) trial conducted in Kenya and Uganda aimed to reduce HIV incidence and improve community health. SEARCH offered HIV and multidisease testing at health fairs followed by home testing for nonparticipants in 32 communities, each with approximately 10 000 persons. In the 16 intervention communities, UNAIDS 90-90-90 targets were achieved within 3 years, reaching '92-95-90' and 79% population-level viral suppression. HIV incidence declined by 32% between year 1 and 3 of follow-up. Key principles of SEARCH's approach included community engagement, integration of HIV with multidisease services, rapid ART start upon HIV diagnosis, and patient-centered, streamlined care. SEARCH's community health approach also reduced HIV mortality, annual TB incidence, and uncontrolled hypertension compared with a country standard of care. Population-level viral suppression increased beyond the UNAIDS 73% target in women and men and reached levels well above recent country estimates across much of sub-Saharan Africa.

Summary: SEARCH provides one example of how to rapidly surpass UNAIDS 90-90-90 targets while addressing community health on the path to HIV epidemic control.

Purpose of review: Sensitive, scalable and affordable assays are critically needed for monitoring the success of interventions for preventing, treating and attempting to cure HIV infection. This review evaluates current and emerging technologies that are applicable for both surveillance of HIV drug resistance (HIVDR) and characterization of HIV reservoirs that persist despite antiretroviral therapy and are obstacles to curing HIV infection.

Recent findings: Next-generation sequencing (NGS) has the potential to be adapted into high-throughput, cost-efficient approaches for HIVDR surveillance and monitoring during continued scale-up of antiretroviral therapy and rollout of preexposure prophylaxis. Similarly, improvements in PCR and NGS are resulting in higher throughput single genome sequencing to detect intact proviruses and to characterize HIV integration sites and clonal expansions of infected cells.

Summary: Current population genotyping methods for resistance monitoring are high cost and low throughput. NGS, combined with simpler sample collection and storage matrices (e.g. dried blood spots), has considerable potential to broaden global surveillance and patient monitoring for HIVDR. Recent adaptions of NGS to identify integration sites of HIV in the human genome and to characterize the integrated HIV proviruses are likely to facilitate investigations of the impact of experimental 'curative' interventions on HIV reservoirs.

Purpose of review: As demand for preexposure prophylaxis (PrEP) increases, we are learning more about what people want from sex and PrEP.

Recent findings: PrEP demand has reached a tipping point in the USA and is increasing rapidly. Although the primary benefit of PrEP use is biological, to reduce risk of HIV infection, PrEP users often express an alternative set of social and emotional benefits that are provided by PrEP. These collateral benefits of PrEP have salience, affect, and are experienced in the present, which are compelling drivers of human behavior. PrEP use has been associated with feeling safe during sex, usually in contrast to ruminations related to fear of HIV or intimate partner violence or control. PrEP can create empowerment, or agency, defined as the capacity and autonomy to act on one's own behalf, because it provides control over one's vulnerability to HIV and relief to women and men who may otherwise worry about whether their partners will use a condom, take antiretroviral therapy, or disclose their HIV status accurately. Planning for sexual and social goals in calm moments is also empowering. These highly desired collateral benefits of PrEP could be undermined, or eliminated, if PrEP is implemented in ways that are coercive or that foment fear of sexual risk compensation, drug resistance, toxicity, or moral judgment.

Summary: Current PrEP implementation provides direct and indirect benefits that are highly desired.