Current HIV Research - Volume 23, Issue 3, 2025

“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.

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.

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.

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 low-productive proliferation of memory CD4⁺ T lymphocytes in INRs.

The concept of same-day antiretroviral therapy (ART) initiation entails initiating HIV treatment promptly upon diagnosis, ideally during the initial clinic visit or even on the same day as diagnosis. This study explores the factors leading to patient loss to follow-up after same-day ART initiation and the benefits and challenges associated with this approach.

A qualitative research design was employed to investigate healthcare providers’ perspectives regarding same-day ART initiation and its contribution to patient loss to follow-up following same-day ART initiation, benefits, and challenges. It is a qualitative study conducted in the form of in-depth cell phone interviews with physicians and nurses who are providing ART services within healthcare facilities in Ethiopia. Data collection was conducted from April 30, 2021, to March 22, 2022.

The findings revealed that same-day ART initiation offers both advantages and drawbacks. Findings show benefits such as shifts in perceptions and attitudes towards HIV, reduced transmission rates, enhanced service utilization, and viral suppression. However, disadvantages included its inappropriateness for critically ill patients’ refusal to accept results and suboptimal adherence, leading to increased risk of patient loss to follow-up.

Same-day ART initiation presents a dual nature, offering immediate benefits in HIV management and transmission reduction, yet facing challenges regarding suitability for critically ill patients and adherence issues. The authors recommend addressing factors such as patient education, stigma reduction, and tailored interventions, which are crucial in optimizing the effectiveness of this approach and minimizing patient loss to follow-up.

The concept of designer exosomes involves developing engineered exosomes to overcome the limitations of natural exosomes in targeted drug delivery and vaccine development.

In this study, the multiepitope constructs were designed based on immunogenic regions of mutant Nef protein of Human Immunodeficiency Virus-1 (HIV-1 Nef^mut) that were prone to high Post-Translational Modifications (PTMs), such as palmitoylation and myristoylation. These constructs with high scores in PTMs were selected for interactions with molecules involved in exosome biogenesis, anchoring of a protein in membranes, and enzymes involved in PTMs (e.g., the mutant enzyme ZDHHC21 p.T209S). Moreover, the selected multiepitope construct with the highest PTM score and stable linkage with these molecules was fused to the first exon of the HIV-1 Tat protein as an antigen candidate, and to GFP as a tracking tool for evaluating their effects on the PTM scores and affinity binding with various molecules.

Our data demonstrated that the multiepitope construct No.13 had better scores for incorporation into exosomes compared to the whole sequences of Nef^mut and wild-type Nef protein (Nef^wt). Furthermore, the linkage of Tat protein to construct No. 13 did not hinder its loading in exosomes compared to GFP, suggesting the use of this construct in vaccine development.

The multiepitope construct No.13 harboring potent Nef^mut epitopes can be applied for linkage with other viral antigens, enhancing their delivery into exosomes for therapeutic applications.

People with limited English proficiency (LEP) experience barriers to healthcare access and optimal outcomes. Language interpretation services can facilitate clear communication-which is key to effective HIV care and treatment.

We analyzed weighted data from the 2019 cycle of the Medical Monitoring Project (MMP), a cross-sectional, complex sample survey of U.S. adults with diagnosed HIV, and data from the 2021 MMP Facility Survey, a survey of facilities providing care to 2019 MMP respondents. We estimated the percentage of people with HIV (PWH) with LEP who received care at facilities offering language interpretation services and facilities providing language interpretation services, overall and by selected characteristics.

Overall, 89.9% of PWH with LEP received care at a facility with language interpretation services, and 83.6% of facilities provided language interpretation services. PWH with LEP who were unemployed were less likely than those who were employed to receive care at a facility with language interpretation services. Facilities that were Federally Qualified Health Centers, were not private practices, received Ryan White HIV/AIDS Program funding, and accepted public health care coverage were more likely to provide language interpretation services than facilities without these characteristics.

Most PWH with LEP obtained HIV care at health care facilities providing language interpretation services, a positive finding as language is a common barrier to accessing care for people with LEP. Most facilities also provided language interpretation services, an important step towards ensuring meaningful access for people with LEP, as required by law.

Our findings demonstrate that most HIV care facilities are providing access to language services to PWH with LEP in the United States.