Current HIV Research - Online First

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.

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.

Plasma samples from all newly reported cases of HIV-1 transmitted through male-to-male 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.

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.

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.

The COVID-19 pandemic caused disruptions in the diagnosis, follow-up and treatment of non-COVID-19 patients due to the burden on the healthcare system. This may lead to missed early diagnosis opportunities in people living with HIV (PLWH). This study aimed to investigate the effects of the COVID-19 pandemic on the demographic characteristics, clinical and laboratory findings, diagnosis, follow-up, and treatment processes of PLWH, and the frequency of opportunistic infections (OIs), AIDS-defining malignancies (ADMs), and late diagnosis (LD).

In this study, 246 PLWH were identified. During the pandemic period, the mean age of PLWH was lower (p=0.025), the use of 2 nucleoside reverse transcriptase inhibitor (NRTI) + protease inhibitor (PI/r) decreased (p=0.026) and antiretroviral therapy (ART) adher-ence was higher (p=0.015). LD (48.8% vs. 47.5%) was similar for the two periods, OIs rate (22.6% vs. 18.5%) was lower and ADMs rate (4.8% vs. 6.2%) was higher in the pandemic period. Our study was designed as a retrospective cohort study. Individuals over the age of 18 years who were newly diagnosed with HIV infection in our hospital between 2018 and 2023 were included in the study.

During the quarantine period, OIs rate (p=0.008) and hospitalization (p=0.002) decreased significantly. Compared to the pre-pandemic period, there was a decrease in primary school graduates (p=0.043) and Centers for Disease Control and Prevention (CDC) category C applicants (p=0.029) and an increase in university graduates (p=0.027) in the quarantine period. After the quarantine period, there was an increase in hospitalization (p=0.002), CDC category C admissions (p=0.021) and ART adherence (p=0.016). Other data were similar for the three periods.

In summary, while the COVID-19 pandemic led to notable changes in patients' characteristics and HIV-related clinical characteristics and treatment, the incidence of LD, OIs and ADMs did not increase significantly. Continued monitoring and adaptation of healthcare services are crucial to managing PLWH effectively in the context of global health crises.

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.

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.

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.

In the changing HIV treatment landscape, the focus shifts to persons living with HIV (PLH) experiencing virological non-suppression on second-line antiretroviral therapy (ART). This includes understanding viral genetic profiles, antiretroviral susceptibility, and the effectiveness of protease inhibitors (PIs) amid evolving dolutegravir-based regimen recommendations.

In this retrospective study, PLH with first-line ART failure transitioned to second-line ART (dual NRTI + ritonavir-boosted PI) between September 2015 and October 2018. Eligible patients were ≥ 13 years old, with ≥ 9 months on first-line ART, and confirmed adherence at first- line regimen failure. Conducted at a Northern Indian tertiary hospital, this 5 year follow-up examined virological outcomes and drug resistance. Follow-up included initial viral-load (VL) and CD4 testing at 6-months, subsequent VL testing every 6-12 months, clinical evaluations, and infection screenings. Data on demographics, treatment history, virological-failure (VF), and drug-resistance testing (DRT) (Viroseq HIV-1 genotyping-system) were analysed using Kaplan-Meier and Competing-risk analysis, with appropriate censoring and imputation for events like death, transfer-out, treatment discontinuation/ interruption, loss to follow-up (LTFU), or ART-regimen change.

219 PLH shifted to ritonavir-boosted PI based second-line ART after 68 (median) months (IQR: 68) of first-line ART exposure and were followed up for 57 (median) months (IQR: 48), totalling 11,548 person-months (PM) of follow-up. Virological outcomes were assessed in 201 PLH. VF cumulative-incidence (Kaplan-Meier-analysis) ranged from 6.9% at 36 months to 15.9% at 60 months. Imputation scenarios showed a potential range, with worst-case incidences of 16.2% at 36 months and 29.4% at 60 months. Cumulative-incidence function (CIF) of VF (Competing-risk-analysis) ranged from 6.5% at 36 months to 12.7% at 60 months. Among 171 PLH with complete VL data, VF incidence was 2.7 per 1000 PM (n=29), with 94.7% achieving nadir VL <1000 cp/mL. VF with PI-mutation (VF-M) analysis, including LTFU patients (n=183), showed CIF for VFM of 2.3% at 36 months and 4.9% at 60 months. DRT (n=23-sequences) revealed 17.4% lopinavir resistance, 34.8% atazanvir resistance, and darunavir (DRV) cross-resistance in three sequences. Overall, 26.1% had no significant drug-resistance mutations, 39.1% had NNRTI resistance, but no PI DRMs, and only 34.8% (of 23-PLH who underwent DRT) potentially required third-line ART.

This 5-year longitudinal study highlights the resilience of PIs in second-line ART. The incidence of VF with PI-resistance was notably low, indicating the ongoing effectiveness of PIs in managing PLH on second-line ART and the possibility of recycling PIs in subsequent ART regimens for these patients. Cross-resistance to DRV patients highlights the need for enhanced treatment monitoring.

Tuberculosis (TB), caused by Mycobacterium tuberculosis, often becomes a comorbidity in individuals infected with Human Immunodeficiency Virus (HIV), the cause of Acquired Immunodeficiency Syndrome (AIDS). HIV-positive individuals have a 30-fold higher risk of contracting TB compared to non-HIV individuals. Assessment of HIV-TB disease progression commonly relies on measuring CD4 cell counts. However, in areas with limited access, the World Health Organization (WHO) recommends using Total Lymphocyte Count (TLC) ≤ 1200 cells/μL as an alternative. Additionally, chest X-rays, a widely accessible radiological method, aid in diagnosing TB in HIV-positive patients, complementing TLC in assessing disease progression in limited facilities.

The objective of this study was to analyze the differences in the location and characteristics of TB lesions based on HIV status and TLC levels.

A case-control study was conducted at Adam Malik Central Hospital on pulmonary TB patients from December 2021 to December 2022, meeting inclusion criteria. Evaluation of TB lesion locations and characteristics was performed by two researchers, while HIV status and TLC data were extracted from medical records.

The study involved 154 subjects, including 77 HIV-positive and 77 non-HIV individuals. The percentage of male participants was 81.8%, with a mean age of 43.4 ± 14.4 years. The significant differences in the characteristics and locations of lesions (cavities, miliary lesions, fibrosis, atelectasis, and upper and lower lung) were revealed in HIV-positive and HIV-negative patients. Similarly, significant differences in the characteristics and locations of lesions (cavities, miliary lesions, fibrosis, atelectasis, and upper and lower lung) were revealed in a patient with TLC ≤ 1200 and TLC > 1200.

The study highlights significant differences in the characteristics and locations of tuberculosis lesions about HIV status and total lymphocyte count levels among pulmonary TB patients. HIV-positive individuals exhibited distinct patterns of TB lesions compared to their HIV-negative counterparts, indicating the impact of HIV on TB disease progression. Furthermore, variations in lesion characteristics were also observed based on TLC levels, with notable differences between patients with TLC ≤ 1200 cells/μL and those with TLC > 1200 cells/μL. These findings underscore the importance of considering both HIV status and TLC in the assessment and management of TB in affected individuals. TLC can serve as an alternative to CD4 measurement in situations where access to CD4 testing is limited.

The increased risk of metabolic syndrome (MetS) and its subcomponents among people living with HIV/AIDS, especially in developing countries, is well documented with the global pooled prevalence of the related risk factors in this population.

This study aimed to explore the prevalence of MetS among Iranian People living with HIV according to the ATP III and Iranian criteria.

The cross-sectional study was conducted on consecutive patients who visited THE referral centre for AIDS/HIV between May to December 2023. A total of 130 participants (n=83; 63.8% male) were investigated based on the inclusion criteria, which included having a minimum age of 25 and a maximum of 65 years and following a stable ART treatment regimen for at least six months. A Chi-square test was used to determine the relationship between the categorical variables. Uni/Multi-variable linear regression analysis was used to quantify the associations between MetS and HIV by the independent variables.

The incidence of MetS according to ATP III and Iranian criteria were 42 (32.3%) and 45 (34.6%), which was higher in older patients (p=0.001) and those with more duration since HIV diagnosis (p=0.02). Around 33.1% and 16.1% were overweight and obese, respectively. Among the components of MetS, the highest prevalence (50.8%) was related to low HDL, and the lowest was related to fasting blood sugar (21.5%). The average body fat mass, protein mass, Soft lean mass, and percentage body fat were 18.54±9.46 kg, 10.91±2.17 kg, 51.31±9.61 kg, and 24.86±10.25% that were higher in MetS group (p<0.05).

Our study points out the high prevalence of MetS in an Iranian population living with HIV, especially those suffering from the underlying disease for a longer time. Conducting multi-centric studies with larger sample sizes is needed to confirm our results and determine the most effective measures.