Current HIV Research最新文献

Despite recent advances in other prevention strategies, an effective vaccine is still needed to guarantee a sustained end to the HIV/AIDS pandemic. However, the traditional ap-proaches of vaccinology have thus far failed to produce an effective vaccine. More basic research may be needed to enhance our understanding of HIV immunity and the immunological principles behind vaccination and to leverage advanced technologies before applied research activities can be successfully used to develop a distributable HIV vaccine. US Government funding plays a crucial role in promoting, enabling, and advising independent scientists and experts to perform such research. This article was written to provide, to the broader scientific community, detail about the tools NIAID uses for research funding, how and why they were used for HIV vaccine development, and how they have been helpful; it is written from the perspective of a Program Officer's experiences while working for more than 25 years in the Division of AIDS (DAIDS) of NIAID at the NIH (the US National Institutes of Health). Several types of funding activities pro-mote HIV vaccine development efforts, but three types of such activities and their impact on HIV vaccine development will be discussed in more detail.

Introduction: The effectiveness of antiretroviral therapy (ART) in treating HIV is in-fluenced by the clinical response of patients, which, in turn, impacts the development of drug resistance. This study aimed to assess the correlation between clinical treatment response and resistance to first-line reverse transcriptase inhibitors in HIV patients receiving treatment for ≤12 and >12 months in South Sulawesi, a province in Indonesia.

Methods: In this cross-sectional study, 36 people living with HIV (PLHIV) experiencing viro-logical failure (VF) were sampled from HIV services in the province from August 2022 to January 2023. HIV-1 viral RNAs were extracted, sequenced, and analyzed for drug sensitivity and re-sistance classification using the Stanford University HIV Drug Resistance Database (HIVdb) ac-cording to World Health Organization (WHO) recommendations, determining resistance levels and HIV subtypes. Phylogenetic analysis of PR-RT sequences (~1200 base pairs) was performed using the Muscle program and MEGA11 software, utilizing the neighbor-joining method with the Kimura two-parameter model.

Results: Genotyping of plasma samples revealed that a significant proportion of patients exhib-ited mutations associated with resistance to both nucleoside reverse transcriptase inhibitors (NRTIs) and non-NRTIs (NNRTIs) (48.6% and 51.4%, respectively). Clinical response indica-tors, such as initial body mass index and occurrence of opportunistic infections, were found to correlate with specific drug resistance, highlighting the importance of monitoring treatment re-sponse. Moreover, virologic response showed strong associations with resistance to specific drugs, suggesting the need for tailored therapeutic approaches. Patient behaviors related to trans-mission risk factors were also found to be linked to resistance levels, underscoring the multifac-torial nature of resistance development.

Conclusion: Overall, this study underscores the importance of considering treatment response in managing HIV and suggests implications for optimizing therapy regimens to mitigate resistance emergence.

This article discusses how the RV144 Phase 3 HIV-1 vaccine trial conducted over 15years ago impacted the subsequent direction of research intended to create and evaluate vaccineswith potentially greater efficacy. Follow-on Phase 2b and Phase 3 trials directly or indirectlyinspired by the modest efficacy reported for the RV144 trial have not shown any significantprotection against HIV-1 acquisition. No credibly protective new immunogens have emergedfrom the Correlates of Protection (CoP) or Risk (CoR) analyses conducted after RV144-inspiredstudies in either humans or various macaque models. Notably, the RV144 trial did not induceneutralizing antibodies (NAbs), only non-NAbs. However, only NAbs have been shown to beprotective in macaque models. One possible but underappreciated explanation for the outcome ofthe RV144 trial could be trained innate immune responses against the non-HIV-1 canarypox virusvector antigens, considering the placebo group only received saline. In this article, the authoroutlines how monkey model research based directly or indirectly on the RV144 trial could stillyield useful information on the possible role of trained immunity in short-term vaccine protection.However, non-human primate research, in general, should now focus on testing new immunogensthat have a reasonable chance of inducing NAbs in humans, rather than expending more resourceson CoP/CoR studies inspired by the RV144 trial and its follow-ups.

Robust assay technologies and reference reagents are essential components in efforts to develop safe and effective antibody-mediated prevention strategies for HIV-1. Here, we de-scribe current approaches used to conduct standardized assessments of neutralizing, binding, and Fc receptor-mediated effector functions of vaccine-elicited antibodies, with an emphasis on recent developments that enable early precursors and intermediates of broadly neutralizing antibodies (bnAbs) to be monitored. We also describe how these assay technologies were adapted to facili-tate clinical evaluations of passively delivered bnAbs for HIV-1 prevention.

Controversy exists around the relative merits of Fc functions in controlling or prevent-ing HIV-1 infection. Proponents point to general correlations of Fc functions with control of HIV, indicating that non-neutralizing antibodies could force immune escape, as observed in the early experiments with Fc mutants of the b12-neutralizing monoclonal antibody. Nay-sayers point to the primary role of neutralization in the control of HIV, the general failure of vaccine trials in-cluding antibodies with Fc functions, and the lack of additional benefit with newer broadly neu-tralizing monoclonal antibodies, such as PGT121. The truth may lie somewhere in between and there are lessons to be learned from the utility of Fc functions in other viral infections. In general, however, the additional benefit of Fc function over and above robust anti-HIV neutralizing anti-bodies may be modest. The intense primary research focus on delivering and inducing potent and broadly neutralizing antibodies, regardless of their Fc function potential, is justified.

An effective HIV-1 vaccine should elicit diverse immune responses, including broadly neutralizing antibodies (bNAbs). Such antibodies recognize regions of the viral envelope glyco-protein (Env) that are conserved among the diverse HIV-1 clades and strains. They are isolated from people living with HIV-1 to protect animals from experimental viral exposure and reduce HIV-1 acquisition in clinical settings. However, despite efforts spanning several decades, bNAbs have not been elicited through immunization. The HIV Env efficiently binds bNAbs, but not their unmutated (germline, gl) precursors. In contrast, Env readily engages the germline precursors of antibodies with no, or very narrow, cross-neutralizing activities (non-neutralizing antibodies, nnAbs). That, in part, explains why Env-based immunogens consistently elicit nnAbs, but not bNAbs. In the past decade, Env-derived proteins have been specifically designed to engage the germline precursors of diverse bNAbs. These 'germline-targeting' Env immunogens activate the corresponding naive B cells in vivo, but are unable to guide their proper maturation towards their broadly neutralizing forms. For this, immunizations with currently not well-defined heterologous Envs are required. Here, we discuss the development of germline-targeting Env immunogens, their in vivo evaluation, and the strategies currently under evaluation that aim to rapidly guide the mat-uration of germline-precursor BCRs into their broadly neutralizing forms.

Background: Since the first recorded HIV-1 infection in 1998, Jiaxing City has seen increasing HIV infections among men who have sex with men (MSM), necessitating targeted research to understand HIV-1 subtypes and drug resistance patterns to improve prevention and treatment strategies.

Objectives: The study aimed to assess the variety of HIV-1 subtypes, the pre-treatment drug resistance (PDR) among MSM in Jiaxing, China, and transmission dynamics of drug-resistant strains. The findings may contribute to the development of targeted HIV prevention and control strategies for the MSM population.

Methods: Plasma samples from all newly reported cases of HIV-1 transmitted through male-tomale sexual contact in Jiaxing City from 2020 to 2022 were retrospectively analyzed. Demographic and epidemiological data were collected. Partial pol gene regions were amplified, sequenced, and analyzed for drug resistance mutations (DRMs) using the Stanford HIV Drug Resistance Database. The Calibrated Population Resistance (CPR) program was utilised to identify Surveillance Drug Resistance Mutation (SDRM). A molecular transmission network was constructed to investigate the scale of transmitted drug resistance (TDR) strains.

Results: We obtained a total of 298 eligible genetic sequences, revealing a diverse distribution of HIV-1 subtypes, with CRF07_BC, CRF01_AE, and CRF55_01B as the most prevalent. Pretreatment DRMs were detected in 91 cases (30.5%), yielding an overall PDR prevalence of 11.0%. Resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) was most frequent (5.4% each). TDR prevalence reached 7.0%, showing an increasing trend (2020-2022). The molecular network analysis indicated sporadic dissemination of drug-resistant cases rather than large-scale transmission chains.

Conclusion: The convergence of high HIV-1 subtype diversity, elevated PDR prevalence, rising TDR rates, and sporadic resistant strain transmission within MSM networks necessitates the sustained resistance surveillance and precision public health interventions.

Aims: In people living with human immune deficiency (PLHIV), the rates of human papillomavirus (HPV) infection, mixed types, and high-risk (HR) strains increase, while the virus clearance does not occur. Here, we report HPV genotyping in PLHIVs from Iran and the Middle East region for the first time.

Methods: HPV genotyping in referring individuals from different provinces to our laboratory was evaluated over 2023-2024. For this, the HPV types in specimens were detected through the INNO- LiPA HPV genotyping kit. Statistical analysis was conducted with a 95% confidence interval (95%CI) and P < 0.05. Accordingly, 481 subjects from various provinces participated in this study.

Results: The rate of HPV infection was 45.7%, of which 14% were HIV-infected women referred from all provinces. The most prevalent types included 6, 51, and 18, but not 16 HR types. Mixed infections in dually infected women were significantly more than in HPV-infected ones. The HPV+/HIV+ subgroup had the lowest median age. The prevalence of HPV types and mixed infection in PLHIVs was congruent with the previous reports, except for the low rate of type 16 infection, perhaps due to the healthy nature of our subjects. Only HIV+/HPV+ cases' age was similar to the previous reports, perhaps because of sample collection and study designs. Among all factors, age and gender affected the HPV type distribution notably.

Conclusion: The current study corroborated the results of many prior reports, demonstrating the considerable impact of HIV status on HPV distribution. The authors recommend implementing a national HPV vaccination and more comprehensive reports of HPV genotyping in PLHIVs.

Background: Family support is an important component of family-oriented care and a vital element in the care of patients with chronic illnesses, including HIV/AIDS. We investigated the association between perceived family support and depression among adolescents living with HIV in northern Nigeria.

Methods: This was a cross-sectional study on 125 adolescents (10-19 years of age) presenting for care at a large urban outpatient HIV clinic in Kano, Nigeria. We assessed family support utilizing the Perceived Social Support Family Scale (PSS-Fa) tool, and depression using the Patient Health Questionnaire-9 (PHQ-9) tool. Logistic regression was done to determine the independent relationship between perceived family support and depression.

Results: Approximately half of the respondents were males (49.6%). The median age (±IQR) of the participants was 16 (± 4) years. The overall prevalence of depression was 56%. More than half (57.6%) of the respondents reported having strong family support. Depression was independently associated with no family support (adjusted odds ratio, aOR = 3.85, 95% confidence interval, CI = 1.10-13.43), weak family support (aOR = 3.16, 95% CI = 1.04-9.63), and feelings of shame about their HIV status (aOR = 5.20, 95% CI = 1.76-15.35).

Conclusion: Depression is common among adolescents presenting for HIV care in northern Nigeria and is independently associated with perceived family support and feelings of shame regarding HIV diagnosis. Our findings support routine screening for depression among adolescents with HIV, coupled with the integration of family-oriented care and counseling into routine HIV services for this population.