Virus Type-1 Infection Research Articles

Dolutegravir metabolism: impact of genetic variations on uridine diphosphate glucuronosyltransferase subfamilies

1. Dolutegravir (DTG) is a key drug used to treat human immunodeficiency virus type-1 (HIV-1) infections. Adverse events (AEs) of DTG treatment, including headache, anxiety, depression, insomnia, and abnormal dreams, are influenced by sex, body weight, age, and serum bilirubin levels. DTG is mainly metabolized by members of the uridine diphosphate glucuronosyltransferase 1A subfamilies (UGT1As), especially UGT1A1. 2. Some studies suggest a relationship between UGT1A1 variants and AEs. The aim of this study was to identify UGT1A isoforms that exhibit DTG glucuronidation activity and determine the relationship between UGT1A variants and DTG glucuronidation in vitro. 3. UGT1A1, UGT1A3, UGT1A9, and UGT1A10 exhibited DTG glucuronidation activity, of which UGT1A1 was the most active. Furthermore, variants of these isoforms showed decreased DTG glucuronidation activity. The different variants of UGT1As, such as UGT1A1.6, UGT1A1.7, UGT1A1.35, UGT1A1.63, UGT1A3.5, UGT1A9.2, UGT1A10M59I, and UGT1A10T202I, showed reduced glucuronidation activity toward DTG in comparison with the wild type UGT1As. 4. This study elucidates the relationship between UGT1A variants and the levels of glucuronidation associated with each variant. 5. Checking for UGT1As may be helpful in predicting potential toxicities and adverse effects related to DTG treatment.

Knowledge and attitude towards Herpes Simplex Virus-2 in Al-Jouf region, Saudi Arabia.

Herpes simplex virus type-2 (HSV-2) infection is a sexually transmitted disease (STD) that causes genital ulcers. The prevalence of HSV-2 increases because of its asymptomatic shedding. This study aimed to evaluate community knowledge and attitude toward HSV-2 infection in Al-Jouf region. 410 participants were enrolled in the study and they filled out a questionnaire on HSV-2 and its complications. Of the 410 participants, 106 individuals were excluded from the study because they resided outside Al-Jouf. Of the remaining 304 participants, 56% were females, 44% were aged between 21-30 years, 84% were university graduates, 56% were single, and 40% were married. Only 58% of participants knew that HSV-2 is an STD, and less than 50% knew that HSV-2 infection can occur many times and can be transmitted from asymptomatic individuals. Regarding their attitude, only 32.5% participants agreed to use a condom if they had sores, 27% agreed to use the condom if they had more than one wife, and more than half of participants responded that they did not know. A considerable proportion of the youth (21-30 years old) did not know that HSV-2 infection is an STD that can occur many times, may remain asymptomatic, and is transmitted from asymptomatic partners or from the mother to her fetus. They were also not aware how to protect themselves from this infectious disease. Thus, educational and health awareness campaigns are required to raise the level of knowledge on HSV-2 infection, including its prevention, and control.

Declining trend of HTLV-1 among organ/ tissue donors in Iranian Tissue Bank between 2014–2021

BackgroundHuman T-cell Lymphotropic Virus type-1 (HTLV-1) infection is associated with serious disorders, including Adult T-cell Leukemia/Lymphoma (ATLL) and HTLV-1–associated myelopathy/tropical spastic paraparesis (HAM/TSP). In addition to sexual, vertical, parenteral, and blood transfusion, organ/tissue transplantation is considered as a transmission route of HTLV infection. Given the substantial risk of HTLV-1 transmission and the subsequent development of HAM/TSP (approximately 40%) in kidney transplant recipients, pre-transplant donor screening is crucial. The present study aimed to investigate the prevalence of HTLV-1 in potential organ/tissue donors referred to the Iranian Tissue Bank and Research Center (ITBRC).Materials and methodsThe study population was potential organ and/or tissue donors referred to ITBRC between 2014 and 2021, including two groups of brain death (potential donors of organs and/or tissues) and circulatory death donors (potential tissue donors from Iranian Legal Medicine Organization). Initial screening was performed using enzyme-linked immunosorbent assay (ELISA), and positive cases were confirmed for HTLV-1 infection with polymerase chain reaction (PCR).Results111 out of 3,814 donors were positive for HTLV-1 (3%). The rate of positive tests between 2014 and 2017 was 6%, which was significantly higher than the positive tests percentage between 2017 and 2021 with 0.5% (P-value < 0.001). The rate of test positivity in females was 4% compared to 2% in males (P-value = 0.001). Furthermore, individuals diagnosed with brain death exhibited a significantly lower likelihood of HTLV-1 infection (0.2%) compared to cases with circulatory death (4%) (P-value < 0.001).ConclusionConsidering the contraindication of organ/tissue donation from donors with HTLV-1 positive test, these findings give an insight into the prevalence of HTLV-1 among potential organ/tissue donors in Iran. Moreover, the higher prevalence of HTLV-1 infection in circulatory death donors from Iranian Legal Medicine Organization urges for cautious evaluation in these donors.

Novel paired CD13-negative (MT-50.1) and CD13-positive (MT-50.4) HTLV-1-infected T-cell lines with differential regulatory T cell-like activity

Adult T-cell leukemia/lymphoma (ATL) occurs after human T-cell leukemia virus type-1 (HTLV-1) infection with a long latency period exceeding several decades. This implies the presence of immune evasion mechanisms for HTLV-1-infected T cells. Although ATL cells have a CD4+CD25+ phenotype similar to that of regulatory T cells (Tregs), they do not always possess the immunosuppressive functions of Tregs. Factors that impart effective immunosuppressive functions to HTLV-1-infected cells may exist. A previous study identified a new CD13+ Treg subpopulation with enhanced immunosuppressive activity. We, herein, describe the paired CD13− (designated as MT-50.1) and CD13+ (MT-50.4) HTLV-1-infected T-cell lines with Treg-like phenotype, derived from the peripheral blood of a single patient with lymphoma-type ATL. The cell lines were found to be derived from HTLV-1-infected non-leukemic cells. MT-50.4 cells secreted higher levels of immunosuppressive cytokines, IL-10 and TGF-β, expressed higher levels of Foxp3, and showed stronger suppression of CD4+CD25− T cell proliferation than MT-50.1 cells. Furthermore, the CD13 inhibitor bestatin significantly attenuated MT-50.4 cell growth, while it did not for MT-50.1 cells. These findings suggest that CD13 expression may be involved in the increased Treg-like activity of MT-50.4 cells. Hence, MT-50.4 cells will be useful for in-depth studies of CD13+Foxp3+ HTLV-1-infected cells.

IgA antibodies against HIV-1

Antibodies, and notably immunoglobulins A (IgA), are paramount in mucosal tissues as protective immune effectors against invading pathogens and immunomodulators of the microbiota. Upon human immunodeficiency virus type1 (HIV-1) infection, systemic and mucosal IgA antibody responses are triggered. While naturally produced serum HIV-1 envelope protein-specific IgA are quantitatively and qualitatively weaker than their IgG counterparts, they also possess antiviral properties including neutralization and Fc-dependent functions. IgA neutralizers can block HIV-1 mucosal transmission in animal models, indicating that their elicitation by vaccination would be an important component for preventing infection. Moreover, the first genuine IgA broadly HIV-1 neutralizing antibodies (bNAbs) were recently identified in certain individuals living with HIV-1. Vaccine-based induction of IgA bNAbs potentially protective at the mucosal level is therefore conceivable. Hence, research efforts must therefore be undertaken to better understand their development and functions. In this review, we present the general functions of IgA in homeostasis and antimicrobial immunity and discuss their involvement in the antibody responses against HIV-1.

Interleukin 1β receptor and synaptic dysfunction in recurrent brain infection with Herpes simplex virus type-1.

Several experimental evidence suggests a link between brain Herpes simplex virus type-1 infection and the occurrence of Alzheimer's disease. However, the molecular mechanisms underlying this association are not completely understood. Among the molecular mediators of synaptic and cognitive dysfunction occurring after Herpes simplex virus type-1 infection and reactivation in the brain neuroinflammatory cytokines seem to occupy a central role. Here, we specifically reviewed literature reports dealing with the impact of neuroinflammation on synaptic dysfunction observed after recurrent Herpes simplex virus type-1 reactivation in the brain, highlighting the role of interleukins and, in particular, interleukin 1β as a possible target against Herpes simplex virus type-1-induced neuronal dysfunctions.

Phytochemical analysis, antiproliferative, antibacterial, antifungal, and antiviral activities of bitter orange (Citrus aurantium) leaf essential oil

The young and old leaves of bitter orange (Citrus aurantium) were examined for their essential oil (EO) compositions, anticancer, antimicrobial, and antiviral activities. The EO yields were 0.77% in young leaves and 0.26% in old leaves. The EO composition showed the predominance of sabinene (37.17%), E-β-ocimene (8.21%), δ-3-carene (7.71%), linalool (7.35%), and limonene (5.43%) in young leaves while of sabinene (47.47%), β-sinensal (5.71%), E-β-ocimene (4.98%), δ-3-carene (4.11%), and β-caryophyllene (4.06%) in old leaves. The EOs of both young and old leaves showed potent cytotoxic activities against human lung carcinoma (A549) and colon adenocarcinoma (DLD-1) cells with IC50 < 0.1 µg/mL. The young leaf EO had higher antibacterial activity than the old leaf EO for all bacterial strains with inhibition zones (IZ) varying from 17 to 45 and 8 to 36 mm, respectively. The EOs of both young and old leaves had strong antifungal activity against all fungal strains with IZ = 90 mm. The young leaf EO was found to be the most active in protecting cells against Herpes simplex virus type-1 (HSV-1) infection during the protection, absorption, and direct periods as compared to the untreated and treated Vero cells except the replication phase.

Combined effect of Neurotropin® and methylcobalamin on postherpetic neuralgia in mice infected with herpes simplex virus type-1

BackgroundPostherpetic pain (PHP) is difficult to control. Although Neurotropin® (NTP) and methylcobalamin (MCB) are often prescribed to treat the pain, the efficacy of combined treatment for PHP remains imcompletely understood. ObjectiveIn this study, we investigate the combined effects of NTP and MCB on PHP in mice. MethodsNTP and MCB were administered from day 10–29 after herpes simplex virus type-1 (HSV-1) infection. The pain-related responses were evaluated using a paint brush. The expression of neuropathy-related factor (ATF3) and nerve repair factors (GAP-43 and SPRR1A) in the dorsal root ganglion (DRG) and neurons in the skin were evaluated by immunohistochemical staining. Nerve growth factor (NGF) and neurotrophin-3 (NT3) mRNA expression levels were evaluated using real-time PCR. ResultsRepeated treatment with NTP and MCB after the acute phase inhibited PHP. Combined treatment with these drugs inhibited PHP at an earlier stage than either treatment alone. In the DRG of HSV-1-infected mice, MCB, but not NTP, decreased the number of cells expressing ATF3 and increased the number of cells expressing GAP-43- and SPRR1A. In addition, MCB, but not NTP, also increased and recovered non-myelinated neurons decreased in the lesional skin. NTP increased the mRNA levels of NTF3 in keratinocytes, while MCB increased that of NGF in Schwann cells. ConclusionThese results suggest that combined treatment with NTP and MCB is useful for the treatment of PHP. The combined effect may be attributed to the different analgesic mechanisms of these drugs.

Proteomic analysis of adult T-cell leukemia/lymphoma: A biomarker identification strategy based on preparation and in-solution digestion methods of total proteins

Adult T-cell leukemia/lymphoma (ATL), caused by human T-cell leukemia virus type-1 (HTLV-1) infection, is a malignant hematologic cancer that remains difficult to cure. We herein established a biomarker identification strategy based on the total cell proteomics of cultured ATL cells to search for novel ATL biomarkers. Four protocols with a combination of selected conditions based on lysis buffers and addition agents for total cell proteomics were used for a differential analysis between the ATL cell group (consisting of 11 cell lines), HTLV-1-infected cell group (consisting of 6 cell lines), and HTLV-1-negative cell group (consisting of 6 cell lines). In the analysis, we identified 24 and 27 proteins that were significantly increased (ratio ≥2.0, p < 0.05) and decreased (ratio ≤ 0.5, p < 0.05), respectively, in the ATL group. Previously reported CCL3 and CD30/TNFRSF8 were confirmed to be among significantly increased proteins. Furthermore, correlation analysis between identified proteins and Tax suggested that RASSF2 and GORASP2 were candidates of novel Tax-regulated factors. The biomarker identification strategy established herein is expected to contribute to the identification of biomarkers for ATL and other diseases.

Molecular pathogenesis of adult T-cell leukemia/lymphoma

Adult T-cell leukemia/lymphoma (ATLL) is an aggressive peripheral T-cell malignancy caused by human T-cell leukemia virus type-1 (HTLV-1) infection. Genetic alterations are thought to contribute to the pathogenesis of ATLL alongside HTLV-1 products such as Tax and HBZ. Several large-scale genetic analyses have delineated the entire landscape of somatic alterations in ATLL, which is characterized by frequent alterations in T-cell receptor/NF-κB pathways and immune-related molecules. Notably, up to one-fourth of ATLL patients harbor structural variations disrupting the 3'-UTR of the PD-L1 gene, which facilitate escape of tumor cells from anti-tumor immunity. Among these alterations, PRKCB and IRF4 mutations, PD-L1 amplification, and CDKN2A deletion are associated with poor prognosis in ATLL. More recently, several single-cell transcriptome and immune repertoire analyses have revealed phenotypic features of premalignant cells and tumor heterogeneity as well as virus- and tumor-related changes of the non-malignant hematopoietic pool in ATLL. Here we summarize the current understanding of the molecular pathogenesis of ATLL, focusing on recent progress made by genetic, epigenetic, and single-cell analyses. These findings not only provide a deeper understanding of the molecular pathobiology of ATLL, but also have significant implications for diagnostic and therapeutic strategies.

HIV-1 infection of genetically engineered iPSC-derived central nervous system-engrafted microglia in a humanized mouse model.

Our mouse model is a powerful tool for investigating the genetic mechanisms governing central nervous system (CNS) human immunodeficiency virus type-1 (HIV-1) infection and latency in the CNS at a single-cell level. A major advantage of our model is that it uses induced pluripotent stem cell-derived microglia, which enables human genetics, including gene function and therapeutic gene manipulation, to be explored in vivo, which is more challenging to study with current hematopoietic stem cell-based models for neuroHIV. Our transgenic tracing of xenografted human cells will provide a quantitative medium to develop new molecular and epigenetic strategies for reducing the HIV-1 latent reservoir and to test the impact of therapeutic inflammation-targeting drug interventions on CNS HIV-1 latency.

Oral Self-Nanoemulsifying System Containing Ionic Liquid of BX795 Is Effective against Genital HSV-2 Infection in Mice.

BX795 is an emerging drug candidate that has shown a lot of promise as a next-generation non-nucleoside antiviral agent for the topical treatment of herpes simplex virus type-1 (HSV-1) and herpes simplex virus type-2 (HSV-2) infections. Our studies indicated that BX795 has limited oral bioavailability, which could be attributed to its low and pH-dependent solubility. Lipid-based formulations such as self-nanoemulsifying systems (SNESs) can improve the solubility and oral bioavailability of BX795, but the poor lipid solubility of BX795 further limits the development of SNES. To improve the loading of BX795 into SNES, we evaluated the ability of various bulky and biocompatible anions to transform BX795 into an ionic liquid (IL) with higher lipid solubility. Our studies showed that sodium lauryl sulfate and docusate sodium were able to transform BX795 into IL. Compared to pure BX795, the developed BX795 ILs showed differential in vitro cytocompatibility to HeLa cells but exhibited similar in vitro antiviral activity against HSV-2. Interestingly, BX795 docusate (BX795-Doc), an IL of BX795 with ∼135-fold higher lipid solubility than pure BX795, could be successfully incorporated into an SNES, and the developed BX795-Doc-SNES could readily form nanoemulsions of size ≤200 nm irrespective of the pH of the buffer used for dilution. Our in vitro studies showed that BX795-Doc-SNES retained the inherent antiviral activity against HSV-2 and showed similar in vitro cytocompatibility, indicating the availability of BX795 from the SNES in vitro. Finally, orally delivered SNES containing BX795-Doc showed a significant reduction in HSV-2 infection in mice compared to the untreated control. Thus, the transformation of BX795 into IL and the subsequent incorporation of the BX795 IL into the SNES are an effective strategy to improve oral therapy of genital herpes infection.

Global Properties of HIV-1 Dynamics Models with CTL Immune Impairment and Latent Cell-to-Cell Spread

This paper presents and analyzes two mathematical models for the human immunodeficiency virus type-1 (HIV-1) infection with Cytotoxic T Lymphocyte cell (CTL) immune impairment. These models describe the interactions between healthy CD4+T cells, latently and actively infected cells, HIV-1 particles, and CTLs. The healthy CD4+T cells might be infected when they make contact with: (i) HIV-1 particles due to virus-to-cell (VTC) contact; (ii) latently infected cells due to latent cell-to-cell (CTC) contact; and (iii) actively infected cells due to active CTC contact. Distributed time delays are considered in the second model. We show the nonnegativity and boundedness of the solutions of the systems. Further, we derive basic reproduction numbers ℜ0 and ℜ˜0, that determine the existence and stability of equilibria of our proposed systems. We establish the global asymptotic stability of all equilibria by using the Lyapunov method together with LaSalle’s invariance principle. We confirm the theoretical results by numerical simulations. The effect of immune impairment, time delay and CTC transmission on the HIV-1 dynamics are discussed. It is found that weak immunity contributes significantly to the development of the disease. Further, we have established that the presence of time delay can significantly decrease the basic reproduction number and then suppress the HIV-1 replication. On the other hand, the presence of latent CTC spread increases the basic reproduction number and then enhances the viral progression. Thus, neglecting the latent CTC spread in the HIV-1 infection model will lead to an underestimation of the basic reproduction number. Consequently, the designed drug therapies will not be accurate or sufficient to eradicate the viruses from the body. These findings may help to improve the understanding of the dynamics of HIV-1 within a host.

Discovery of unusual phloroglucinol–triterpenoid adducts from Leptospermum scoparium and Xanthostemon chrysanthus by building blocks-based molecular networking

The first phloroglucinol-triterpenoid hybrids, myrtphlotritins A–E (1–5), were rapidly recognized and isolated from two species of Myrtaceae by employing the building blocks-based molecular network (BBMN) strategy. Compounds 1–5 featured new carbon skeletons in which phloroglucinol derivatives were coupled with lupane- and dammarane-type triterpenoids through different linkage patterns. Their structures and absolute configurations were elucidated by comprehensive analysis of spectroscopic data and quantum chemical calculations. Biosynthetic pathways for compounds 1–5 were proposed on the basis of the coexisting precursors. Guided by the biogenetic pathways, the biomimetic synthesis of compound 1 was also achieved. Additionally, compounds 2, 3, and 5 exhibited potent antiviral activities against herpes simplex virus type-1 (HSV-1) infection, and compounds 2 and 5 displayed significant anti-inflammatory activities on RAW264.7 cells.

HTLV-1 Proviral Load in Vaginal Fluid Correlates with Levels in Peripheral Blood Mononuclear Cells.

The prevalence of human T-lymphotropic virus type-1 (HTLV-1) infection is higher in women, and sexual intercourse has been described as an important route of male-to-female transmission. The present study aimed to quantify HTLV-1 proviral load (PVL) in vaginal fluid, and to investigate correlations with PVL in peripheral blood mononuclear cells (PBMCs). In addition, cytopathological alterations and vaginal microbiota were evaluated. HTLV-1-infected women were consecutively recruited at a multidisciplinary center for HTLV patients in Salvador, Brazil. All women underwent gynecological examinations to obtain cervicovaginal fluid and venipuncture for blood collection. PVL, as measured by real-time quantitative polymerase chain reaction (RT-qPCR), was expressed as the number of copies of HTLV-1/106 cells in blood and vaginal fluid samples. Light microscopy was used to assess cervicovaginal cytopathology and vaginal microbiota. In the 56 included women (43 asymptomatic carriers and 13 diagnosed with HTLV-1-associated myelopathy/tropical spastic paraparesis-HAM/TSP), mean age was 35.9 (SD ± 7.2) years. PVL was higher in PBMCs (median: 23,264 copies/106 cells; IQR: 6776-60,036) than in vaginal fluid (451.9 copies/106 cells; IQR: 0-2490) (p < 0.0001). PVL in PBMCs was observed to correlate directly with PVL in vaginal fluid (R = 0.37, p = 0.006). PVL was detected in the vaginal fluid of 24 of 43 (55.8%) asymptomatic women compared to 12 of 13 (92.3%) HAM/TSP patients, p = 0.02. Cytopathologic analyses revealed no differences between women with detectable or undetectable PVL. HTLV-1 proviral load is detectable in vaginal fluid and correlates directly with proviral load in peripheral blood. This finding suggests that sexual transmission of HTLV-1 from females to males may occur, as well as vertical transmission, particularly in the context of vaginal delivery.

Inhibition of matrix metalloproteinases by HIV-1 integrase strand transfer inhibitors.

More than fifteen million women with the human immunodeficiency virus type-1 (HIV-1) infection are of childbearing age world-wide. Due to improved and affordable access to antiretroviral therapy (ART), the number of in utero antiretroviral drug (ARV)-exposed children has exceeded a million and continues to grow. While most recommended ART taken during pregnancy suppresses mother to child viral transmission, the knowledge of drug safety linked to fetal neurodevelopment remains an area of active investigation. For example, few studies have suggested that ARV use can be associated with neural tube defects (NTDs) and most notably with the integrase strand transfer inhibitor (INSTI) dolutegravir (DTG). After risk benefit assessments, the World Health Organization (WHO) made recommendations for DTG usage as a first and second-line preferred treatment for infected populations including pregnant women and those of childbearing age. Nonetheless, long-term safety concerns remain for fetal health. This has led to a number of recent studies underscoring the need for biomarkers to elucidate potential mechanisms underlying long-term neurodevelopmental adverse events. With this goal in mind, we now report the inhibition of matrix metalloproteinases (MMPs) activities by INSTIs as an ARV class effect. Balanced MMPs activities play a crucial role in fetal neurodevelopment. Inhibition of MMPs activities by INSTIs during neurodevelopment could be a potential mechanism for adverse events. Thus, comprehensive molecular docking testing of the INSTIs, DTG, bictegravir (BIC), and cabotegravir (CAB), against twenty-three human MMPs showed broad-spectrum inhibition. With a metal chelating chemical property, each of the INSTI were shown to bind Zn++ at the MMP's catalytic domain leading to MMP inhibition but to variable binding energies. These results were validated in myeloid cell culture experiments demonstrating MMP-2 and 9 inhibitions by DTG, BIC and CAB and even at higher degree than doxycycline (DOX). Altogether, these data provide a potential mechanism for how INSTIs could affect fetal neurodevelopment.

Seroprevalence of maternal peripartum human T-cell lymphotropic virus type-1 infection: a systematic review and meta-analysis of the Nigerian literature.

The peripartum period is both a highly vulnerable stage and a significant indicator of a population's health status. Interest is increasing in human T-cell lymphotropic virus type-1 (HTLV-1) transmission due to its adverse health impacts. However, nationally representative data on HTLV-1 that are important for health planning are unavailable for this subpopulation. This study aimed to conduct a pooled estimate of HTLV-1 prevalence among pregnant women in Nigeria to quantify its clinical burden and public health implications. This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis 2020 statement. After a systematic review of the Nigerian literature, 12 studies (2,821 pregnant or postnatal women) were included in the final evidence synthesis. The estimated HTLV-1 prevalence in Nigerian peripartum women following a positive screening test by enzyme-linked immunosorbent assay was 5.44% (95% confidence interval [CI], 3.16%-9.20%). A subgroup analysis of the 2 major regions showed a slightly higher prevalence in the Western versus Southern region (5.55% [95% CI, 2.49%-11.87%]; and 4.91% [95% CI, 2.11%-11.02%]; P=0.84). However, a subgroup analysis by geopolitical zone revealed that Southwestern and Northwestern Nigeria had the highest prevalence (9.23% [95% CI, 4.35%-18.55%; I2=93%] and 7.15% [95% CI, 1.54%-27.54%]; I2=92%). Our decade-old subgroup analysis found inconsistencies in the HTLV-1 prevalence. Furthermore, our literature review revealed a prevalence of HTLV infection among patients with various clinical types of lymphomas/leukemias and myelopathy of 2%-22%. These findings have important implications in defining the epidemiological patterns of HTLV-1 infection in Nigeria. They also suggest the presence of HTLV-endemic clusters near low-endemic areas, even within the same geopolitical zones.

HIV-1 Integrase Strand Transfer Inhibitors and Neurodevelopment.

Children born to mothers, with or at risk, of human immunodeficiency virus type-1 (HIV-1) infection are on the rise due to affordable access of antiretroviral therapy (ART) to pregnant women or those of childbearing age. Each year, up to 1.3 million HIV-1-infected women on ART have given birth with recorded mother-to-child HIV-1 transmission rates of less than 1%. Despite this benefit, the outcomes of children exposed to antiretroviral drugs during pregnancy, especially pre- and post- natal neurodevelopment remain incompletely understood. This is due, in part, to the fact that pregnant women are underrepresented in clinical trials. This is underscored by any potential risks of neural tube defects (NTDs) linked, in measure, to periconceptional usage of dolutegravir (DTG). A potential association between DTG and NTDs was first described in Botswana in 2018. Incidence studies of neurodevelopmental outcomes associated with DTG, and other integrase strand transfer inhibitors (INSTIs) are limited as widespread use of INSTIs has begun only recently in pregnant women. Therefore, any associations between INSTI use during pregnancy, and neurodevelopmental abnormalities remain to be explored. Herein, United States Food and Drug Administration approved ARVs and their use during pregnancy are discussed. We provide updates on INSTI pharmacokinetics and adverse events during pregnancy together with underlying mechanisms which could affect fetal neurodevelopment. Overall, this review seeks to educate both clinical and basic scientists on potential consequences of INSTIs on fetal outcomes as a foundation for future scientific investigations.

Cervical Cytology and Herpes Simplex Virus Type-2 Serology Among Human Immune Deficiency Virus Infected Women on Highly Active Antiretroviral Therapy in Enugu, Nigeria.

The prevalence of Human Immunodeficiency Virus (HIV) and Herpes Simplex Virus type-2 (HSV-2) infections are high and the programme for Cervical Cancer Screening is weak in Nigeria. Prevalence of Herpes Simplex Virus Type-2 co-infection and cervical cytology among HSV-2 co-infected Human Immunodeficiency Virus Sero-positive (HIV+) women on Highly Active Antiretroviral Therapy (HAART) attending Human Immunodeficiency Virus clinic at University of Nigeria Teaching Hospital (UNTH) Ituku/Ozalla Enugu, Nigeria. A cross-sectional, hospital-based study. Active participants included 105 HIV seropositive women on HAART and104 HIV seronegative (HIV-) women who passed inclusion criteria and signed written informed consent. Each participant was coded with a specific number. A structured questionnaire was used to obtain the socio-demographic and medical history. Serum was obtained for HSV-2 serology test for all participants and HIV screening for HIV-negative participants. Cervical smears were collected for Papanicolaou stains and Immunocytochemistry using anti-P16INKa antibody. Prevalence of HSV-2+ was 50.5% among HIV+ women on HAART and 16.3% among HIV- women, Odds Ratios [95% CI]; p-value was 5.21 [2.74-9.94]; p < 0.0001. HIV+ women on HAART co-infected with HSV-2 significantly had more Cervical Lesions, 11.4% compared to HIVwomen uninfected with HSV-2, 4.8%, OR [95% CI]; p-value 4.8 (1.58-14.54); p = 0.006. The prevalence of HSV-2 was significantly high among HIV+ women on HAART. HSV-2+ co-infection could be an enhancer of Cervical Lesions among HIV+ women on HAART. Hence, anti-herpetic agent introduction and screening for HSV-2 among HIV+ patients are recommended.

The role of IL-1β during human immunodeficiency virus type1 infection.

Interleukin (IL)-1β is a key innate cytokine that is essential for immune activation and promoting the inflammatory process. However, abnormal elevation in IL-1β levels has been associated with unwanted clinical outcomes. IL-1β is the most extensively studied cytokine among the IL-1 family of cytokines and its role in pathology is well established. During the course of human immunodeficiency virus type 1 (HIV-1) infection, the level of this proinflammatory cytokine is increased in different anatomical compartments, particularly in lymphatic tissues, and this elevation is associated with disease progression. The aim of this review is to address the pathological roles play by IL-1β in the light of enhancing HIV-1 replication, driving immune cell depletion, and chronic immune activation. The role of IL-1β in HIV-1 transmission (sexually or vertically 'from mother-to-child') will also be discussed. Additionally, the impact of the available antiretroviral therapy regimens on the levels of IL-1β in HIV-1 treated patients is also discussed. Finally, we will provide a glance on how IL-1β could be targeted as a therapeutic strategy.