This article discusses how the RV144 Phase 3 HIV-1 vaccine trial conducted over 15 years ago impacted the subsequent direction of research intended to create and evaluate vaccines with potentially greater efficacy. Follow-on Phase 2b and Phase 3 trials directly or indirectly inspired by the modest efficacy reported for the RV144 trial have not shown any significant protection against HIV-1 acquisition. No credibly protective new immunogens have emerged from the Correlates of Protection (CoP) or Risk (CoR) analyses conducted after RV144-inspired studies in either humans or various macaque models. Notably, the RV144 trial did not induce neutralizing antibodies (NAbs), only non-NAbs. However, only NAbs have been shown to be protective in macaque models. One possible but underappreciated explanation for the outcome of the RV144 trial could be trained innate immune responses against the non-HIV-1 canarypox virus vector antigens, considering the placebo group only received saline. In this article, the author outlines how monkey model research based directly or indirectly on the RV144 trial could still yield 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 immunogens that have a reasonable chance of inducing NAbs in humans, rather than expending more resources on 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.
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.
Introduction/objective: "Immunological non-responders" (INRs) are individuals living with HIV who are undergoing Highly Active Antiretroviral Therapy (HAART) but fail to restore their CD4⁺ T-cells count despite effective viral control. The incomplete immune restoration in INRs is often associated with the low-productive proliferation of memory CD4⁺ T lymphocytes. The ability of CD4⁺ T cells to divide is critically dependent on the glycolytic pathway, which supplies the necessary energy and building blocks for cell division. We hypothesize that impaired glycolytic activity in the memory CD4⁺ T cells of INRs contributes to their ineffective proliferation, ultimately limiting immune restoration.
Methods: This study involved two groups of HIV-infected HAART-treated subjects: INR and Immunological Responders (IR). A third group consisted of healthy controls, comprising uninfected volunteers. To identify the metabolic factors contributing to immunological non-response to therapy, glucose uptake, and lactate production were measured in the memory CD4⁺ T cells from all three groups.
Results: INR had the highest activation level in memory CD4+ T cells and the greatest glucose uptake. However, both groups of HIV-infected patients had significantly reduced lactate production compared to the healthy donors. Short-term phytohemagglutinin stimulation provoked an increase in lactate production in memory CD4+ T lymphocytes. Nevertheless, we found significantly reduced lactate production levels in activated memory CD4+ Т cells of INR an IR.
Conclusion: In INRs, there is a discrepancy between the highly activated phenotype of memory CD4⁺ T lymphocytes and their glycolytic activity. This reduced glycolysis may explain the lowproductive proliferation of memory CD4⁺ T lymphocytes in INRs.
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.
Anti-Retroviral Therapy (ART) is a fundamental principle in the management of Human immunodeficiency virus (HIV) infection, significantly improving the quality of life for individuals living with the virus. However, the success of ART crucially depends on patient adherence to complex medication regimens that come with the therapy. Patients must meticulously adhere to their prescribed treatment plans to maintain viral suppression and prevent the progression of HIV. Medication adherence, a multifaceted challenge in healthcare, becomes particularly entangled within the realm of ART. Patients are often prescribed a combination of antiretroviral medications, each with unique dosing schedules and dietary requirements as instructed by the physician. For individuals with varying levels of health literacy, language proficiency, and cultural backgrounds, comprehending and adhering to these regimens can be overwhelming and challenging. Non-adherence to these medications can result in treatment failure, drug resistance, and compromised health outcomes that burden the healthcare systems. In that perspective, the role of pictograms as visual aids emerges as part and parcel of patient education and counseling within healthcare systems. Pictograms are graphical representations of concepts or actions designed to transcend linguistic and literacy barriers. When used in conjunction with ART, they simplify complex medication instructions, empower patients with knowledge, and improve adherence. Generally, the role of pictograms in supporting medication adherence and patient counseling in antiretroviral therapy is a powerful testament that serves a purpose in bridging communication and literacy gaps within the healthcare systems. By simplifying complex medication regimens, empowering patients with knowledge, and fostering adherence, pictograms contribute to better health outcomes and the overall success of ART. As healthcare providers and systems continue to harness the potential of pictograms, patient education and adherence in the management of HIV and other chronic conditions stand to be greatly enhanced.
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