Antiretroviral Research Articles

Systemic Immune-Inflammation-Based Biomarker and Fragility Fractures in People Living With HIV: A 10-Year Follow-Up Cohort Study in China.

Fragility fractures are a significant concern among people living with HIV(PLWH) due to the combined effects of chronic inflammation, immune dysregulation, and antiretroviral therapy. Traditional biomarkers have limited predictive value for fragility fractures in this population. This study aims to evaluate the systemic immune inflammation-based scores as novel biomarkers for predicting fragility fractures in PLWH in China. We conducted a cohort study of PLWH in the orthopedic department of Beijing Ditan Hospital from January 2011 to September 2023. We monitored fragility fractures and collected data on demographics, clinical characteristics, and laboratory parameters. Multivariate Cox and logistic regression models were used to assess the predictive value of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), and systemic inflammation response index (SIRI) for fragility fractures. Restricted cubic splines (RCS) were employed to explore potential nonlinear relationships, and subgroup analyses were conducted to examine the stability of these associations. During a median follow-up of 5.5 years, our study included 1148 PLWH patients, and 204 patients (17.8%) experienced fragility fractures. After adjusting for all covariates, SII and SIRI were identified as independent risk factors for fragility fractures in PLWH, whereas NLR, PLR, and MLR were not. Patients with higher levels of SII and SIRI had a significantly increased risk of fragility fractures compared to those with lower levels (HR: 1.96, 95% CI: 1.24-3.10, p = 0.004; HR: 1.83, 95% CI: 1.16-2.88, p = 0.009). RCS analysis indicated a stable linear relationship between SIRI and fragility fractures. Furthermore, KM curves demonstrated that patients with higher SII and SIRI scores had a higher likelihood of experiencing fragility fractures. Our research shows that SII and SIRI are promising biomarkers for predicting fragility fractures in PLWH. Clinicians should consider incorporating SIRI into clinical practice to improve fracture risk stratification and guide preventive strategies for this vulnerable population.

Global, regional, and national prevalence of HIV-1 drug resistance in treatment-naive and treatment-experienced children and adolescents: a systematic review and meta-analysis

Despite significant reductions in mother-to-child HIV-1 transmission risks due to the advancements and scale-up of antiretroviral therapy (ART), the global burden of HIV-1 drug resistance (HIVDR) in treatment-naive and treatment-experienced children and adolescents remains poorly understood. In this study, we conducted a systematic review and meta-analysis to estimate the prevalence of HIVDR in these populations globally, regionally, and at the country level. We systematically searched PubMed, Embase, and Web of Science for studies reporting HIVDR in treatment-naive and treatment-experienced children and adolescents from inception to June 28, 2024. Eligible studies reported at least ten successfully genotyped cases. We excluded studies where drug resistance was not reported separately for children and adults or for treatment-naive and treatment-experienced populations. The methodological quality of eligible studies was assessed, and random-effect models were used for meta-analysis to determine the pooled overall and regimen-specific prevalence of one or more HIVDR mutations in these populations globally, regionally, or at the country level. This study is registered with PROSPERO under the number CRD42023424483. Of 2282 records identified, 136 studies (28,539 HIV-1-infected children from 52 countries) were included for analysis. The overall prevalence of HIVDR is 26.31% (95% CI, 20.76-32.25) among treatment-naive children and 74.16% (95% CI, 67.74-80.13) among treatment-experienced children (p<0.0001). HIVDR varied widely across subregion with the highest prevalence in Southern Africa (37.80% [95% CI, 26.24-50.08]) and lowest in South America (11.79% [95% CI, 4.91-20.84]) for treatment-naive children while highest in Asia (80.85% [95% CI, 63.76-93.55]) and lowest in Europe (54.39% [95% CI, 28.61-79.03]) for treatment-experienced children. The proportion of viral failure (VF) presented positive correlation with DR prevalence for treatment-experienced children, which increased from 61.23% (95% CI, 47.98-73.72) in proportion of VF<50%-81.17% (95% CI, 71.57-89.28) in proportion of 100%. Meta-regression analysis for both groups showed that only age (naive: p=0.0005; treated: p<0.0001) was the sources of heterogeneity. Non-nucleoside reverse transcriptase inhibitor (NNRTI) resistances were the most seen mutations among the treatment-naive group, with the HIVDR prevalence more than 10% in Southern Africa, Western and Central Africa, Eastern Africa, Asia, and North America. Both nucleoside reverse transcriptase inhibitor (NRTI) and NNRTI resistances were commonly seen among the treatment-experienced group, varying from 36.33% (95% CI, 11.96-64.93) in North America to 77.54% (95% CI, 62.70-89.58) in South America for NRTI and from 39.98% (95% CI, 13.47-69.97) in Europe to 68.86 (95% CI, 43.91-89.17) in Asia for NNRTI, respectively. This study underscores the significant burden of HIVDR among children and adolescents worldwide, particularly pronounced in sub-Saharan Africa and low-income countries. It emphasizes the critical importance of surveillance in all HIV-1-infected children and advocates for the adoption of dolutegravir (DTG) or other optimal formulations as first-line ART in settings where NNRTI resistance exceeds the WHO's 10% threshold. DTG's high resistance barrier, potent antiviral efficacy, and favorable safety profile makes it a superior choice for managing drug-resistant HIV-1, surpassing traditional antiretroviral therapies. This work was supported by the Science and Technology Innovation Committee of Shenzhen Municipality (No. JCYJ20220531102202005) and the Natural Science Foundation of Guangdong Province (No. 2024A1515012118).

Identification of a Novel HIV‐1 Integrase Strand Transfer Inhibitor: A Synergistic Approach Combining Pharmacophore Modelling and In Vitro Assays

BackgroundAIDS is a highly prevalent and life‐threatening global epidemic that severely compromises the host's immune system, increasing vulnerability to opportunistic diseases. The absence of definitive curative drugs emphasizes the importance and necessity of discovering novel anti‐HIV agents.ObjectiveThis study aims to discover a natural molecular entity that acts as an Integrase strand transfer inhibitor (INSTI) with enhanced potency against HIV.MethodsA ligand‐based pharmacophore model was developed for 4 FDA‐approved INSTIs, with the potential for treating HIV‐1. AutoDock facilitated molecular docking and free energy calculation to discern IN activity. Subsequently, MD simulations assessed interaction stability. ADMET analysis preceded an in vitro anti‐HIV strand transfer assay.ResultsThe generated model revealed a specific interaction involving Mg2+ ion chelation. Crucial residues of HIV‐1 IN and their respective free‐binding energies were identified. The lead compound exhibited superior in silico characteristics which were substantiated by 100 ns MD simulations and MM‐PBSA analysis. Additionally, the in vitro assay demonstrated potent inhibition with the lowest IC50, forming strong molecular interactions with IN.ConclusionThese findings showed valuable insights for the strategic development of new antiretroviral treatments (ART), paving the path for the development of natural therapeutic agents for HIV treatment.

Epidemiological and virological characteristics of people living with HIV on antiretroviral treatment for more than 6 months in virological failure in Brazzaville, Republic of Congo

Introduction. Virological failure is one of the main causes of failing to treat, and better management of HIV infection requires understanding and controlling the factors that contribute to this phenomenon. The main objective was to characterize the patients of the active file of the Brazzaville Outpatient Treatment Center in virological failure to identify predictive factors leading to virological failure. Methods. Conducted between June and December 2020, this was a cross-sectional study. Patients enrolled were HIV-1-infected patients from the Brazzaville Outpatient Treatment Center receiving a potent combination therapy for at least 6 months but experiencing virological failure. Viral load was measured using the automated Abbott Real-time HIV-1 m2000rt System. Sociodemographic and clinical data were collected from a computerized patient record software called Santia. For the identification of the independent predictors of virological failure, statistical analysis was performed. Results. A total of 109 patients with virological failure were recruited. The median age of the patients was 45 years (interquartile range: 37–52 years) and women were more represented (74%). More than half of the patients had World Health Organization stage IV HIV and the median duration of antiretroviral treatment was 96 months. The most followed treatment regimen was AZT+3TC+EFV (or nevirapine) with 48%, while the median viral load was 12985 copies ml−1. Conclusion. In our study, we did not identify any sociodemographic or clinical variables predictive of virological failure. However, we felt that it would be desirable to carry out a study with temporal follow-up and the possibility of sequencing in order to identify the different circulating genotypes and resistance mutations.

Navigating the Roadblocks: Progress and Challenges in Cell-Based Therapies for Human Immunodeficiency Virus.

Cell-based therapies represent a major advancement in the treatment and management of HIV/AIDS, with a goal to overcome the limitations of traditional antiretroviral therapy (ART). These innovative approaches not only promise a functional cure by reconstructing the immune landscape but also address the persistent viral reservoirs. For example, stem cell therapies have emerged from the foundational success of allogeneic hematopoietic stem cell transplantation in curing HIV infection in a limited number of cases. B cell therapies make use of genetically modified B cells constitutively expressing broadly neutralizing antibodies (bNAbs) against target viral particles and infected cells. Adoptive cell transfer (ACT), including TCR-T therapy, CAR-T cells, NK-CAR cells, and DC-based therapy, is adapted from cancer immunotherapy and repurposed for HIV eradication. In this review, we summarize the mechanisms through which these engineered cells recognize and destroy HIV-infected cells, the modification strategies, and their role in sustaining remission in the absence of ART. The review also addresses the challenges to cell-based therapies against HIV and discusses the recent advancements aimed at overcoming them.

LITERATURE REVIEW ON HPLC METHODS FOR ESTIMATION OF EMTRICITABINE AND TENOFOVIR DISOPROXIL FUMARATE TABLETS

Emtricitabine and Tenofovir Disoproxil Fumarate (TDF) are essential components of antiretroviral therapy (ART) for HIV infection. Accurate quantification of these drugs in pharmaceutical formulations is crucial for ensuring therapeutic efficacy and patient safety. High-Performance Liquid Chromatography (HPLC) is a widely used analytical technique for this purpose. Several validated HPLC methods have been developed, employing diverse chromatographic conditions and detection techniques. These methods typically utilize reversed-phase C18 columns and UV detection at 260 nm or 270 nm. Key considerations for method development include selectivity, sensitivity, accuracy, precision, linearity, and robustness. Additionally, other analytical techniques such as Ultra-High Performance Liquid Chromatography (UHPLC), Thin-Layer Chromatography (TLC), Fourier Transform Infrared Spectroscopy (FTIR), and Ultraviolet-Visible (UV-Vis) Spectroscopy have been explored for the analysis of Emtricitabine and TDF. However, HPLC remains the preferred method due to its versatility, sensitivity, and reliability.

Association between differentiated HIV care delivery model and low-level viremia among people living with HIV in Rwanda

BackgroundLow-level viremia (LLV) (HIV-RNA 51–999 copies/mL) is associated with increased risk of non viral load suppression (HIV-RNA ≥ 1000 copies/mL). We assessed the association between differentiated service delivery model (DSDM) and LLV among people living with HIV (PLHIV) in Rwanda.MethodsWe conducted a retrospective cohort analysis using routinely collected data of adults living with HIV from 28-healthcare facilities in Rwanda before and after the introduction of DSDM. Under DSDM, PLHIV initiated treatment within seven days of HIV diagnosis and medication pick-up up to six months for those with sustained viral load suppression suppression. Proportions of LLV at 6,12 and 18 months were quantified. Multivariable log binomial regression models were used to assess the effect of DSDM on LLV. To handle missing data, multiple imputations was performed.ResultsOf 976 people living with HIV, 645(66.0%) were female and 463(47.4%) initiated treatment during DSDM. The median age was 37 (interquartile range: 32–43) years. LLV was 7.4%, 6.6% and 5.4%, at 6,12 and 18 months, respectively. Compared to those who initiated treatment before DSDM, starting treatment during DSDM increased six-month LLV [adjusted risk ratio (aRR) = 2.8: 95%CI (1.15–6.91)] but not at 12 [aRR = 2.3: 95%CI (0.93–5.75)] and 18 months [aRR = 0.3: 95%CI (0.09–1.20)]. Using imputed datasets, the association between DSDM and LLV persisted.ConclusionsDSDM was associated with increased risk of LLV at 6-months. possibly due to the minimal amount of time PLHIV had in pondering and accepting the HIV diagnosis. Continued support is needed among people receiving early antiretroviral therapy initiation to prevent development of LLV.

P28 Immune reconstitution-induced sarcoidosis following initiation of antiretroviral therapy in an HIV-positive patient

P28 Immune reconstitution-induced sarcoidosis following initiation of antiretroviral therapy in an HIV-positive patient

Immune Reconstitution Inflammatory Syndrome in HIV Patients Diagnosed with Brain Imaging

Highly active antiretroviral therapy improves immune function in human immunodeficiency virus patients but can lead to progressive multifocal leukoencephalopathy (PML) due to immune reconstitution inflammatory syndrome (IRIS). PML, caused by John Cunningham (JC) virus, affects the central nervous system in immunocompromised individuals. Despite the negative result for JC virus in the cerebrospinal fluid test, we report a rare case of PML-IRIS that was diagnosed based on clinical presentation and brain magnetic resonance imaging findings and showed improvement with steroid therapy.

Population-Specific Predictors of Immunologic Reconstitution Following Initiation of Combined Antiretroviral Therapy in Children: A Retrospective Observational Study from a 15-Year Cohort of HIV-Positive Children and Adolescents in Eritrea.

In the landscape of HIV treatment, combined antiretroviral therapy (cART) is a cornerstone in managing viral loads and boosting CD4+ T-cell counts. Nevertheless, disparities in treatment outcomes remain persistent, and a subset of children fail to achieve adequate immunologic reconstitution (IR). This study aims to investigate the demographic and clinical factors associated with inadequate IR in HIV-infected children in Eritrea. A retrospective observational study was conducted on 822 children followed at Orotta National Pediatric Referral Hospital between 2005 and 2020. Two distinct analyses were performed, with univariate and multivariate logistic regression models employed to investigate risk factors contributing to inadequate immunologic reconstitution (IR) at the study endpoints of 6- and 12-months post-cART initiation. From the initial cohort of 822 patients [53.4% were males, cohort median age at cART initiation was 78 (IQR: 48-101) months and median absolute CD4 count 270 (151-441) cells/µL]. Two separate analyses were conducted on two cohort subsets with complete data, including 456 children at the 6-month mark and 495 children at 12 months of follow-up. Following 6 months on cART, Immunologic reconstitution was achieved in 87.8% (95% CI: 84.3-91.2) and increased to 90.4% (95% CI: 87.3-93.5) after 12 months of treatment. Independent predictors of inadequate IR after 6 months of cART were higher baseline absolute CD4 counts (aOR = 1.003, (95% CI: 1.002-1.005); p-value <0.001) and NNRTI (EFV: aOR = 3.9, (95% CI: 1.3-11.9); p-value = 0.01). Meanwhile, gender (females: aOR = 0.3, (95% CI: 0.1-0.9, p-value = 0.03) and higher baseline absolute CD4 counts (aOR = 1.003, (95% CI: 1.002-1.005); p-value < 0.001) were independent risk factors of inadequate IR after 12 months of treatment. The study underscores the interplay of baseline CD4 count, gender, and regimen choice in shaping the effectiveness of cART in children. Lower baseline absolute CD4 count was associated with IR after starting cART. Notably, children on EFV had a higher likelihood of inadequate IR after 6 months, and male children were more prone to insufficient IR at 12 months. Targeting these population-specific factors may be pivotal in advancing gender-responsive therapeutic strategies and improving health outcomes for HIV-infected children in sub-optimal clinical settings and resource-constrained environments.

Bell’s palsy characteristics, clinical manifestations, complications, and prognosis in a primary care setting, a single center study: A retrospective cohort study

ABSTRACT Background: Bell’s palsy (BP) is a cranial nerve disorder in which unilateral or bilateral paralysis of the facial nerve occurs. The study aims to study BP’s characteristics, including its clinical manifestations, prognosis, and complications among adult patients aged 18 years and above. Methods: A retrospective study of adult patients diagnosed with BP in a primary care setting] [January 2015 to December 2022]. Results: The study included a total number of 92 patients with an incidence rate of 23 cases per 100,000 people. The mean age was 43.52 years. The most common symptoms reported were dropping of the mouth at 38.9%, loss of forehead muscle movement at 24.4%, loss of nasolabial fold at 22.2%, loss of facial expressions at 20%, and headache at 18.9%. Immunodeficiency affected 2.3% of the patients. The management of patients involved the use of steroids in 76.1% and the use of antiretroviral medications in 48.9%. Physiotherapy was used in 29.5%. The complete recovery rate during the first year was 90.8%. The rate of complete recovery within two years was 96.9%. Conclusion: The incidence of BP in the region seems to be similar to the incidence rate reported elsewhere in the world. The use of antiviral therapy seems to be high despite the controversy around the use of antivirals in the management of BP. The majority of patients with BP recover within the first year.

Gilead under fire over HIV drug licensing

Gilead under fire over HIV drug licensing

MPO interacts with hRSV particles, contributing to the virucidal effects of NETs against clinical and laboratory hRSV isolates

Human Respiratory syncytial virus (hRSV) mainly affects immunosuppressed patients requiring hospitalization. No specific treatment is financially accessible, and available vaccines do not cover all risk groups. During hRSV infection, there is a robust neutrophilic influx into the airways. hRSV-activated neutrophils release substantial neutrophil extracellular traps (NETs) in lung tissue, comprising DNA, histones, cytosolic, and granular proteins. NETs form mucus buildup in the lungs, compromising respiratory capacity and neutralizing viral particles. Understanding responsible NETs molecules requires improvement. We evaluated NETs interacting with hRSV particles and their contribution to anti-hRSV NET effects. Immunoblotting, immunoprecipitation, and peptide sequencing assays confirmed hRSV binding to a 50–75 kDa NET protein, Myeloperoxidase (MPO). MPO, a microbicide enzyme in NETs, interacts with hRSV, likely at F0 protein (site IV) on the viral surface. Additionally, MPO (32 μM) and NETs (0.4 μg/mL) reduced in vitro replication of clinical (hRSV A and B) and laboratory (Long) hRSV isolates by approximately 30 %, reversible by selective MPO inhibitor (PF-06281355; 48 μM). Thus, MPO contributes to virucidal NET effects on diverse hRSV strains, enhancing comprehension of NETs' role in infection and aiding treatment strategies for respiratory diseases.

Use of an Ethinyl Estradiol/Etonogestrel Vaginal Ring Alters Vaginal Microbial Communities in Women with HIV.

HIV-1 antiretroviral therapy (ART) alters hormonal contraceptive levels delivered via intravaginal ring (IVR) in a regimen specific manner. We explored the role of the IVR on vaginal microbial communities, vaginal short chain fatty acids (SCFAs), vaginal HIV shedding, and the effect of vaginal microbes on hormone concentrations in cisgender women with HIV (WWH). Vaginal microbes were assessed by 16S RNA sequencing of weekly vaginal swabs, vaginal SCFA by mass spectrometry, HIV-1 shedding by nucleic acid amplification on vaginal aspirates, and bacterial vaginosis by Nugent scoring from 74 participants receiving an etonorgestrel/ethinyl estradiol (ENG/EE) intravaginal ring while on no ART (N=25), efavirenz-based ART (N=25), or atazanavir-based ART (N=24). At baseline, microbial communities of the 64 substudy eligible participants robustly classified as Lactobacillus crispatus--dominant (n=8), L. gasseri-dominant (n=2), L. iners-dominant (n=17), or mixed anaerobic communities (n=37). During IVR therapy, there was an increased probability of Lactobacillus-dominant community state types (CSTs) (odds-ratio=1.61, p=0.04). Vaginal CSTs were associated with Nugent scores. Bacterial vaginosis-associated bacteria were associated with significantly higher and L. iners with lower Nugent Scores (all p adj <0.1). Lactic acid levels were correlated with the relative abundance of Lactobacillus species (r2=0.574; p<0.001). Vaginal shedding of HIV-1 was less common in women with L. crispatus-dominant microbiomes (p=0.04). Mixed anaerobic vaginal communities modulated EE concentrations in a regimen-specific manner. Combined ENG/EE IVR therapy was associated with an increase in Lactobacillus-dominant vaginal microbial communities in WWH and may benefit those with bacterial vaginosis. EE levels were altered by the vaginal microbiota.

HIV disease progression among heterosexually-infected individuals before the introduction of universal ART in China: A linear mixed-effects model.

In 2016, China introduced universal antiretroviral therapy (ART) for all HIV-infected individuals regardless of CD4 cell count. However, the natural history and rate of CD4 count decline among heterosexually-infected individuals remain uncharacterized. Analyzing national surveillance data can address this gap and shed light on the pathogenesis of HIV in this population. We used a linear mixed-effects model to assess CD4 trajectory over time before ART initiation and estimated the median time from HIV seroconversion to reaching CD4 thresholds of < 500, < 350, and < 200 cell/mm3. From the Chinese HIV/AIDS Comprehensive Response Information Management System, 59,085 eligible individuals were identified, with 113 having data to estimate the date of HIV seroconversion. The linear mixed-effects models estimated an intercept of 23.64 (95% confidence interval [CI]: 22.41 to 24.87) and a slope of -1.32 (95% CI: -1.34 to -1.30) for males, and an intercept of 22.70 (95% CI: 21.00 to 24.40) and a slope of -1.29 (95% CI: -1.31 to -1.27) for females. The estimated median times from HIV seroconversion to reaching CD4 count thresholds of < 500, < 350, < 200 cells/mm3 were 0.97, 3.74, and 7.20 years for males, and 0.26, 3.09, and 6.48 years for females, respectively. Males consistently took longer to reach these CD4 count thresholds compared to females of the same age group. Older individuals (≥ 40 years) reached CD4 thresholds faster than younger individuals (15-29 years), indicating more rapid disease progression in older people living with HIV.

Prevalence and predictors of precancerous cervical lesions among women living with HIV in Libreville, Gabon

BackgroundHIV-infected women are at an increased risk of developing precancerous cervical lesions (PCL) than non-infected women. In Gabon, no data exists on the prevalence of PCL among women living with HIV. The aim of this study was to assess the prevalence and risk factors associated with the development of PCL among HIV-positive women in Libreville, Gabon.MethodologiesThis was a retrospective study carried out within the Gynecology and Obstetrics Department of University Hospital Center of Libreville (CHUL) from January to August 2016. It included women registered at the HIV Clinic of Nkembo, and screened for PCL or cervical cancer (CC). Descriptive statistics were used to characterize sociodemographic data and the prevalence of PCL. The chi square and odd-ratio tests were used to evaluate the associations between PCL, CD4 count, antiretroviral use, age at first sexual intercourse, number of sexual partner tobacco, and contraception use.ResultsAmong the 115 HIV-positive women recruited, 33 (28.70%; SD ± 0.45) were diagnosed with PCL. 79.1% of them were on antiretroviral therapy (ART), and the mean CD4 cell count value was 411.74 cells/mm3 (SD ± 241.77). Being on ART, age, number of sexual partners, contraceptive use and smoking were not risk-factors linked with the development of PCL. CD4 cell count was the only associated risk-factors (p-value: 0.02).ConclusionThe incidence of PCL among HIV-infected is high in Libreville, Gabon, especially among those with baseline CD4 counts < 200 cells/mm3. This study recommends screening for cervical cancer for all HIV-infected women.

Immuno-hematological parameters among adult HIV patients before and after initiation of Dolutegravir based antiretroviral therapy, Addis Ababa, Ethiopia.

Immuno-hematological abnormalities are common among HIV infected individuals as well as patients with highly active antiretroviral therapy (HAART). However, the immuno-hematological outcome of Dolutegravir based antiretroviral therapy (ART) usage is not well investigated. To assess hematological and immunological parameters among adult HIV patients before and after initiation of Dolutegravir based ART regimen at St. Peter Specialized Hospital, Addis Ababa, Ethiopia. A cross-sectional study was conducted from May to July 2021 at St. Peter Specialized Hospital among adult HIV patients. A total of 422 HIV patients on Dolutegravir based ART (combination of Dolutegravir/lamivudine/tenofovir disoproxil fumarate (DTG/3TC/TDF)) for a minimum of 3 months were selected using convenient sampling methods. Socio-demographic as well as clinical data of the participants was obtained using pre-tested structured questionnaires and a review of medical records. Hematological parameters such as CBC was obtained using Beckman coulter automated hematology analyzer and immunological parameters such as CD4 count were determined using BD FACS presto. Statistical analysis of the data was done using SPSS version 21. Paired t-test was used to compare dependent variables before and after initiation of the new HAART and binary logistic regression was used to determine predictors of immuno-hematological abnormalities. P-value < 0.05 was considered as statistically significant. Of 422 adult HIV patients, about 273(64.7%) were females. The mean age of study participants was 42.2 years (±10.4SD). The mean white blood cell (WBC) count, red blood cell (RBC) count, hemoglobin (Hb), platelet distribution width (PDW), CD4 count, as well as lymphocyte percentage, neutrophil percentage, and platelet counts (PLT) were increased significantly(P<0.05) after 3 months of the Dolutegravir based therapy. While, red cell distribution width (RDW) and mean cell hemoglobin (MCH) were decreased (P<0.05) after the treatment. Other hematological parameters such as mean cell volume (MCV), hematocrit (HCT), mean cell hemoglobin concentration (MCHC), mean platelet volume (MPV) and platelet distribution width (PDW) showed no significant change. On the other hand, the most common hematological abnormalities identified after the new HAART were anemia (12.1%); followed by Leucopenia (11.3%), neutropenia (6%), and thrombocytopenia (4%). Anemia was associated with female sex (AOR = 7.8, 95% CI: 1.9-32.2, P<0.005) and WHO clinical stage III/IV (AOR = 16, 95% CI: 10.63-66.46, P<0.01). There was a significant change in certain immuno-hematological parameters such as WBC count, RBC count, PLT count, Hb, PDW, CD4 count, lymphocyte and neutrophil percentage after initiation of the Dolutegravir based therapy. Anemia was the most common hematological abnormality. Further studies are required to fully comprehend the outcome of the new treatment regimen on immuno-hematological parameters.

The factor structure of the Centre for Epidemiological Studies Depression Scale (CESD-R-20) among South African antiretroviral therapy users

Depression is a significant concern for people living with HIV and AIDS as it is associated with negative health outcomes and suboptimal adherence to antiretroviral therapy (ART). To this extent, screening for depression is essential for early detection. The CESD-R-20 is a revised four-factor questionnaire developed to assess depressive symptoms in adults. This study explored the factor structure and psychometric properties of the CESD-R-20 among 685 individuals receiving ART. Data were collected at the Infectious Diseases Clinic of a large public hospital outside Cape Town from participants who had been receiving ART for at least six months. Exploratory factor analysis (EFA) of the CESD-R-20 was performed to identify its underlying factor structure. The EFA revealed a one-factor solution termed “depressive affect,” comprising 19 items that encompassed the original factors. This finding suggests that depression is a cohesive construct rather than a collection of interconnected dimensions. The scale exhibited high internal consistency (Cronbach’s alpha = 0.95) among the sample of persons living with HIV and AIDS. Our findings indicate that the CESD-R-20 can effectively measure depressive affect as a one-factor scale in South Africans receiving ART. The scale demonstrated strong internal consistency and is suitable for screening for depressive symptoms among persons living with HIV and AIDS.

A Sensitivity and Consistency Comparison Between Next-Generation Sequencing and Sanger Sequencing in HIV-1 Pretreatment Drug Resistance Testing

Next-generation sequencing (NGS) for HIV drug resistance (DR) testing has an increasing number of applications for the detection of low-abundance drug-resistant variants (LA-DRVs) in regard to its features as a quasi-species. However, there is less information on its detection performance in DR detection with NGS. To determine the feasibility of using NGS technology in LA-DRV detection for HIV-1 pretreatment drug resistance, 80 HIV-infected individuals who had never undergone antiretroviral therapy were subjected to both NGS and Sanger sequencing (SS) in HIV-1 drug resistance testing. The results reported in this study show that NGS exhibits higher sensitivity for drug resistance identification than SS at a 5% detection threshold. NGS showed a better consistency compared with that of SS for both protease inhibitors (PIs) and integrase inhibitors (INSTIs), with a figure amounting to more than 90%, but worse consistency in nucleotide reverse transcriptase inhibitors (NRTIs), with a consistency ranging from only 61.25% to 87.50%. The consistency of non-nucleotide reverse transcriptase inhibitors (NNRTIs) between NGS and SS was around 85%. NGS showed the highest sensitivity of 87.0% at a 5% threshold. The application of NGS technology in HIV-1 genotype resistance detection in different populations infected with HIV requires further documentation and validation.

Hepatic steatosis-insulin resistance and type 2 diabetes in people with HIV at diagnosis: effect of initial antiretroviral therapy.

We evaluated the impact of hepatic steatosis-insulin resistance (HS-IR) and liver fibrosis (LF) on type 2 diabetes mellitus (DM2) using triglyceride-glucose (TyG) and Fibrosis-4 (FIB-4). The incidence of DM2 was 12.9 [95% confidence interval (CI), 16.9-9.7] and 9.8 (95% CI, 6.9-13.6) per 1000 person-years in HS-IR and LF. The prevalence of HS-IR was significantly lower at 12 and 24 months with TDF + (3TC or FTC) + RPV [hazard ratio (HR) 0.5 [95% CI, 0.3-0.8], P < 0.01 at 12 months; 0.6 [0.4-0.9], P = 0.01 at 24 months].