Current HIV Research - Volume 21, Issue 3, 2023

Viruses belong to the class of micro-organisms that are well known for causing infections in the human body. Antiviral medications are given out to prevent the spread of disease-causing viruses. When the viruses are actively reproducing, these agents have their greatest impact. It is particularly challenging to develop virus-specific medications since viruses share the majority of the metabolic functions of the host cell. In the continuous search for better antiviral agents, the United States Food and Drug Administration (USFDA) approved a new drug named Evotaz on January 29, 2015 for the treatment of human immunodeficiency virus (HIV). Evotaz is a combined once-daily fixed drug, containing Atazanavir, an HIV protease inhibitor, and cobicistat, an inhibitor of the human liver cytochrome P450 (CYP) enzyme. The medication is created such that it can kill viruses by concurrently inhibiting protease and CYP enzymes. The medicine is still being studied for a number of criteria, but its usefulness in children under the age of 12 is currently unknown. The preclinical and clinical characteristics of Evotaz, as well as its safety and efficacy profiles and a comparison of the novel drug with antiviral medications presently available in the market, are the main topics of this review paper.

Retrovirus integration is an obligatory step for the viral life cycle, but large amounts of unintegrated DNA (uDNA) accumulate during retroviral infection. For simple retroviruses, in the absence of integration, viral genomes are epigenetically silenced in host cells. For complex retroviruses such as HIV, preintegration transcription has been found to occur at low levels from a large population of uDNA even in the presence of host epigenetic silencing mechanisms. HIV preintegration transcription has been suggested to be a normal early process of HIV infection that leads to the syntheses of all three classes of viral transcripts: multiply-spliced, singly-spliced, and unspliced genomic RNA; only viral early proteins such as Nef are selectively translated at low levels in blood CD4 T cells and macrophages, the primary targets of HIV. The initiation and persistence of HIV preintegration transcription have been suggested to rely on viral accessory proteins, particularly virion Vpr and de novo Tat generated from uDNA; both proteins have been shown to antagonize host epigenetic silencing of uDNA. In addition, stimulation of latently infected resting T cells and macrophages with cytokines, PKC activator, or histone deacetylase inhibitors has been found to greatly upregulate preintegration transcription, leading to low-level viral production or even replication from uDNA. Functionally, Nef synthesized from preintegration transcription is biologically active in modulating host immune functions, lowering the threshold of T cell activation, and downregulating surface CD4, CXCR4/CCR5, and HMC receptors. The early Tat activity from preintegration transcription antagonizes repressive minichromatin assembled onto uDNA. The study of HIV preintegration transcription is important to understanding virus-host interaction and antagonism, viral persistence, and the mechanism of integrase drug resistance. The application of unintegrated lentiviral vectors for gene therapy also offers a safety advantage for minimizing retroviral vector-mediated insertional mutagenesis.

Introduction: Children who are HIV-exposed but uninfected (CHEU) are at risk of linear growth faltering and neurodevelopmental delay. Circulating biomarkers associated with these adverse outcomes may elucidate pathways of injury. Objective: To identify biomarkers associated with growth faltering and neurodevelopmental delay in CHEU. Methods: We performed a systematic review of electronic databases MEDLINE (1946-April 2021), EMBASE (1974-April 2021), Scopus (2004-April 2021), and PubMed (1985-April 2021), following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The systematic review was registered on the International Prospective Register of Systematic Reviews (PROSPERO, registration number CRD42021238363). Results: We found seven studies associating biomarker abnormalities and growth outcomes in CHEUs and two studies on biomarker abnormalities and neurodevelopmental delay. Biomarker abnormalities associated with growth restriction were: C-reactive protein (CRP), tumour necrosis factor (TNF), interferon-gamma (IFN-γ), interleukin (IL)-12p70, IFN-γ-induced protein-10 (CXCL10/IP-10), lipopolysaccharide binding protein (LBP), insulin-like growth factor-1 (IGF-1), and IGF-binding protein-1 (IGFBP-1). Biomarkers associated with motor, language, and cognitive delay were CRP, IFN-γ, IL-1β, -2, -4, -6, -10, -12p70, neutrophil gelatinase-associated lipocalin (NGAL), granulocyte-macrophage colony-stimulating factor (GM-CSF), and matrix metalloproteinase- 9 (MMP-9). Conclusion: Elevated markers of inflammation (acute phase reactants, pro-inflammatory cytokines, chemokines) and intestinal microbial translocation are associated with growth faltering. Elevated markers of inflammation are associated with adverse neurodevelopment.

Aim: Weight gain with the use of dolutegravir, bictegravir, and tenofovir alafenamide for antiretroviral therapy has been reported. However, studies on changes in body composition and the leptin/adiponectin ratio after antiretroviral therapy initiation are limited. These factors are important because they can be used as indicators of metabolic syndrome and cardiovascular disease risk. Introduction: This study aimed to investigate the changes in waist circumference, body composition, and adipokine levels after the initiation of antiretroviral therapy consisting of dolutegravir, bictegravir, and tenofovir alafenamide and evaluate the relationships between these parameters in Japanese patients living with human immunodeficiency virus. Methods: This is a single-center, prospective, observational study. Waist circumference, body composition, and adipokine levels were measured at baseline and 12 months after antiretroviral therapy initiation in antiretroviral therapy-naive Japanese patients living with human immunodeficiency virus. Body composition was determined by bioelectrical impedance analysis. Results: We included 11 patients (10 bictegravir/TAF/emtricitabine, 1 dolutegravir/lamivudine) in this study. The results showed no significant changes in waist circumference and body composition among the patients. The leptin/adiponectin ratio and serum leptin levels significantly increased after antiretroviral therapy initiation. Changes in waist circumference, fat mass, and visceral fat area showed a strong positive correlation. Conclusion: The leptin/adiponectin ratio increased following antiretroviral therapy initiation. The waist circumference measurement can be a simple, inexpensive, and useful method to identify changes in fat mass and visceral fat area after initiation of antiretroviral therapy.

Background: Non-alcoholic fatty liver disease (NAFLD) has become a significant cause of mortality and morbidity in people living with HIV. Objective: We aimed to investigate NAFLD presence by magnetic resonance imaging (MRI) methods, including MRI-derived proton density fat fraction (MRI-PDFF) and MRE, and ultrasound elastography among Turkish people living with HIV (PLWH), and identify factors correlated with fatty liver. Methods: We included 57 PLWH attending outpatient clinics on antiretroviral therapy (ART) for more than six months, without HBV/HCV co-infection, significant alcohol consumption, active opportunistic infection, previously diagnosed hepatobiliary disease, T2DM, and hyperlipidemia. We performed MRI, MRE, and US elastography on all participants. Results: The mean age of the participants (M/F, 47/10) was 41.7± 12 years. The median duration of HIV infection was 3 (0.5-19 years) years. The mean MRI-PDFF was 4.4 ± 3.8 %, and 11 had fatty liver. The mean MRE value was 2.27 ± 0.6 kPa, inflammation was present in 16, and 4 participants had values consistent with fibrosis. The mean US elastography of the study population was 4.1±2.4 kPa. The mean right and left CCA intima-media of the study population was 0.65± 0.23 mm and 0.66± 0.25 mm; 16 had increased intima-media thickness. In patients with fatty liver, a significant positive correlation was present between MRE and CCA intima-media thickness (rs=0.82, p:0.006 for MRE-left CCA; r=0.68, p=0.042 for MRE-right CCA). Conclusion: We demonstrated that even a significant proportion of PLWH individuals with normal transaminase levels have fatty liver. Future prospective trials are warranted to understand and mitigate the risk factors, course of NAFLD, and accurate non-invasive tests, predicting fibrosis in people living with HIV.

Background: Since the beginning of the HIV epidemic, the virus has taken millions of lives worldwide. The United Nations AIDS Fund’s statistics reported that deaths caused by HIVrelated conditions and AIDS were about 39 million from the beginning of the epidemic to 2015. The united global efforts to fight the virus are considerably changing the indicators, such as mortality and morbidity, but the challenges remain. The total number of people living with HIV in Bulgaria as of 12th May, 2015, was 2,121. As of 30th November, 2016, the official data reported 2 460 people living with HIV. As of 13th February, 2017, 2 487 individuals were HIV-seropositive. Approximately 60% of people with HIV are prone to developing cognitive impairment due to the infection. Objective: This study aimed to know the level of cognitive deficiency, in particular, the verbal and semantic fluency of people living with HIV and AIDS. Methods: In this study, a comparative analysis was carried out. The Stewart test was used to compare the average independent samples. For clarity, the average values, the test statistics, and the estimated significance levels are presented in the tables. Additionally, a statistical mechanism of factor selection was used by the forward stepwise method. The Wilks' Lambda statistic reported values between 0 and 1, with values close to zero indicating good discrimination of the model. Results: According to this research, the HIV positives participants generated fewer verbs than the ones from the control group. The data were partially confirmed by the present study. There were differences in terms of both adjectives and nouns among people living with HIV and AIDS. Conclusion: The study data proves that language deficits are detectable in neurocognitive testing of HIV. The overall hypothesis of the study has been confirmed. The language impairments are primarily qualitative and can be used as a marker for the initial and subsequent therapy assessment.

Introduction: Human immunodeficiency virus (HIV) infection, the etiological agent of acquired immunodeficiency syndrome (AIDS), is a serious public health issue. Therapeutic measures have been successful in increasing the survival and improving the quality of life. However, some treatment-naive subjects living with HIV present resistance-associated mutations as a result of late diagnosis and/or mutant strain infections. The objective of this study was to identify the virus genotype and assess the antiretroviral resistance profile based on the results of HIV genotyping in treatment-naive subjects living with HIV, after six months of taking antiretroviral therapy. Methods: This was a prospective cohort study on treatment-naive adults living with HIV attending a specialized outpatient clinic in southern Santa Catarina State, Brazil. The participants were interviewed and had blood samples drawn. The genotypic antiretroviral drug resistance profile was examined in patients with detectable viral loads. Results: 65 treatment-naive subjects living with HIV were recruited for this study. After six months of taking antiretroviral therapy, resistance-associated mutations were observed in 3 (4.6%) subjects living with HIV. Conclusion: Subtype C was identified as the circulating subtype in southern Santa Catarina State, and L10V, K103N, A98G, and Y179D were the most common mutations found in treatment-naive subjects.