Human Immunodeficiency Virus Resistance Research Articles

Carbapenem Resistance among HIV-Infected Patients: A Scoping Review

Background: Antibiotic resistance is an escalating global health concern, with carbapenems, potent last-line antibiotics, facing increasing resistance and potentially dire consequences. This scoping review sought to consolidate data on carbapenem resistance in human immunodeficiency virus (HIV)-infected patient cohorts as the intricate relationship between HIV and antibiotic resistance remains inadequately understood. Methods: We employed a scoping review methodology and conducted a comprehensive search across Google Scholar, Scopus, Cochrane, and PubMed, utilizing specific search terms related to carbapenem resistance and HIV. We extracted and analyzed data, encompassing study design, geographic location, number of HIV-infected participants, CD4 cell counts, specimen types, cultured organisms, carbapenem susceptibility, and comparisons between HIV-infected and uninfected cohorts. Results: This review encompassed 15 studies, involving 2365 HIV-infected participants, primarily employing cross-sectional designs, with nine studies conducted in African countries. The most frequently analyzed specimens included urine, stool, and sputum, with Escherichia coli emerging as the most frequently cultured organism. Commonly used carbapenem drugs included imipenem, meropenem, and ertapenem, with varying susceptibility patterns. Imipenem and meropenem exhibited sensitivities exceeding 80%, except for one study with Pseudomonas aeruginosa, which demonstrated 73% sensitivity. Ertapenem displayed fluctuating sensitivities ranging from 58% to 100% for different bacterial organisms. Only one study reported the colonization of carbapenem-resistant Enterobacterales (CRE) in HIV-infected patients, with HIV status not significantly influencing CRE carriage. When comparing HIV-infected and uninfected cohorts, four studies found no substantial impact of HIV status on carbapenem resistance. Conclusion: In the context of the HIV burden and opportunistic infections, carbapenem resistance demonstrated relatively consistent patterns across most studies comparing HIV-infected and uninfected cohorts. However, the presence of CRE among HIV-infected individuals raises concerns regarding nosocomial infections. The limited reporting of CD4 counts in the included studies necessitates further exploration of potential associations with immune status. E. coli, frequently cultured in these studies, exhibited varying resistance patterns, and the impact of HIV on these patterns remains uncertain. Carbapenem susceptibility displayed variability among different organisms, underscoring the nuanced nature of resistance. As such, this scoping review serves as a foundation for comprehending carbapenem resistance in HIV-infected populations but underscores the necessity for more comprehensive research in this field.

Changes in Primary HIV-1 Drug Resistance Due to War Migration from Eastern Europe

In recent years, especially as a result of war in Ukraine, enormous movements of migration to Poland from eastern European countries have been reported, including people living with Human Immunodeficiency Virus (HIV). We have conducted multi-center, prospective study, which aimed to establish HIV-1 subtype and assess the presence of primary drug resistance mutations to nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and protease inhibitors in antiretroviral treatment naïve patients. The clinical trial recruited 117 individuals during 2 years period (2020–2022). The prevalence of HIV-1 subtype A was statistically significantly more frequent in Ukrainian, and HIV-1 subtype B in Polish patients (p < 0.05). Drug resistance mutations were detected in 44% of all cases and the comparison of presence of mutations in the analyzed groups, as well as in the subgroups of subtype A and B HIV-1 has not revealed any significant differences (p > 0.05), nevertheless Polish patients had multidrug resistance mutations more frequent (p < 0.05). The results from our trial show no increased risk of transmission of multidrug resistant HIV strains in our cohort of Ukrainian migrants.Clinical trials. Gov number NCT04636736; date of registration: November 19, 2020.

HIV Pre-Exposure Prophylaxis, Blood Donor Deferral, Occult Infection, and Risk of HIV Transmission by Transfusion: A Fine Balance Between Evidence-Based Donor Selection Criteria and Transfusion Safety.

Pre- and postexposure prophylaxis for human immunodeficiency virus (HIV) are key to reducing the transmission of this virus. Furthermore, low-toxicity, long-acting formulations provide additional clinical benefits, in particular easier adherence to treatment and prevention. However, breakthrough HIV infections can occur despite the use of pre-exposure prophylaxis (PrEP), mainly due to suboptimal adherence or multi-drug resistant HIV strains. Albeit rare, PrEP breakthrough infections have also been reported in fully adherent patients. Should such breakthrough infection occur in an eligible blood donor, PrEP might suppress viremia and delay antibody seroconversion, thereby masking the infection and increasing the risk of transfusion transmission. This possibility has raised concerns in the blood transfusion community but remains little documented. Therefore, a literature search was performed to assess the state of knowledge on the risk of PrEP breakthrough infection, with a particular focus on the risk of HIV entering the blood supply. Evidently, PrEP breakthrough infections are rare, although the risk is not zero. Moreover, a fraction of individuals - including blood donors - do not disclose PrEP use according to various surveys and measurements of HIV PrEP analytes. Additionally, viremia and seroconversion may remain undetectable or close to the limit of detection for a long time after cessation of PrEP, particularly with long-acting antiretrovirals. Therefore, current recommendations to defer donors for at least 3 months after the last dose of oral PrEP or 2 years for long-acting PrEP appear justified, as they safeguard the blood supply and public trust toward the system. These recommendations help to safeguard blood safety and public trust in the blood supply.

Molecular Pathogenesis of Human Immunodeficiency Virus-Associated Disease of Oropharyngeal Mucosal Epithelium.

The oropharyngeal mucosal epithelia have a polarized organization, which is critical for maintaining a highly efficient barrier as well as innate immune functions. In human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) disease, the barrier and innate immune functions of the oral mucosa are impaired via a number of mechanisms. The goal of this review was to discuss the molecular mechanisms of HIV/AIDS-associated changes in the oropharyngeal mucosa and their role in promoting HIV transmission and disease pathogenesis, notably the development of opportunistic infections, including human cytomegalovirus, herpes simplex virus, and Epstein-Barr virus. In addition, the significance of adult and newborn/infant oral mucosa in HIV resistance and transmission was analyzed. HIV/AIDS-associated changes in the oropharyngeal mucosal epithelium and their role in promoting human papillomavirus-positive and negative neoplastic malignancy are also discussed.

Integration of Quality Management Systems in a Rural, Low-Resource Environment: The Experience at Phebe Hospital in Bong County, Liberia

Laboratory strengthening programs have been limited to clinical testing for prioritized diseases such as Ebola Virus Disease (EVD), Lassa Fever, COVID-19, Multidrug Resistant Tuberculosis, Malaria, and Human Immunodeficiency Virus (HIV). While patient outcomes are key concerns, limited efforts have been directed at improving Quality Management Systems (QMS). The benefits of QMS are correlated to improved patient care in resource-limited settings. This article examines the ability of a laboratory in a low-resource setting to integrate QMS into clinical care, describes its challenges, and measures its benefits on improved treatment outcomes. Gap analysis was conducted to implement QMS at Phebe Hospital, Bongo county, Liberia. We prioritized the framework of workflow processes and reorganization, equipment and inventory management, and documentation as challenges hampering the effective implementation of QMS. As a stepwise intervention strategy, laboratory workflow and infrastructure were remodeled, staff retrained, partners managed, and system changes were communicated to strengthen the laboratory systems. Improvement in communicating goals to clinicians, following work plans, managing staff time, delegating responsibilities, allocating resources, and strategically managing the presence of multiple partners as effective strategies to improve QMS were observed. We demonstrated that improving QMS strengthens the laboratory systems at Phebe Hospital. To sustain such initiative, Phebe Hospital must focus efforts on building sustainable laboratory systems and structures. We propose future studies to evaluate the short- and long-term benefits of such interventions.

Different Pathways Conferring Integrase Strand-Transfer Inhibitors Resistance.

Integrase Strand Transfer Inhibitors (INSTIs) are currently used as the most effective therapy in the treatment of human immunodeficiency virus (HIV) infections. Raltegravir (RAL) and Elvitegravir (EVG), the first generation of INSTIs used successfully in clinical treatment, are susceptible to the emergence of viral resistance and have a high rate of cross-resistance. To counteract these resistant mutants, second-generation INSTI drugs have been developed: Dolutegravir (DTG), Cabotegravir (CAB), and Bictegravir (BIC). However, HIV is also able to develop resistance mechanisms against the second-generation of INSTIs. This review describes the mode of action of INSTIs and then summarizes and evaluates some typical resistance mutations, such as substitution and insertion mutations. The role of unintegrated viral DNA is also discussed as a new pathway involved in conferring resistance to INSTIs. This allows us to have a more detailed understanding of HIV resistance to these inhibitors, which may contribute to the development of new INSTIs in the future.

Investigation of Drug-resistance substitutions in HIV-1 RT Protein in Iranian HIV Infected Patients

Abstract: &#x0D; Background:&#x0D; Currently, more than 37 million people are living with human immunodeficiency virus type 1. Reverse transcription (RT) is a main part in the life cycle of retroviruses which is responsible for synthesis of DNA complementary to an RNA or DNA template. Recently several inhibitors have been introduced to target RT protein; however, drug resistance is one of the greatest challenges in the improvement of effective treatment for human immunodeficiency virus (HIV) infection. Here, we determined the resistance mutations in the RT gene in treatment failure patients and searched for the dominant subtype among them. &#x0D; Methods:&#x0D; HIV viral load and a reverse transcriptase nested polymerase chain (RT-nested PCR) reactions were performed in 15 patients with treatment failure to amplify the RT gene. Drug resistance mutations, as well as the viral subtypes, were analyzed using by using several bioinformatics software and online tools.&#x0D; Results: &#x0D; The frequency of RT related drug-resistance mutations in patients was 33.3%, among which the major mutation consisted of 20% of all those occurring in codon 184. Moreover, the results showed 6.6% and 26.6% of patients were resistant to Non-Nucleoside RT Inhibitor (NNRTIs) and Nucleoside RT Inhibitors (NRTIs), respectively. In addition, the vast majority of samples (12 patients of 15) belonged to subtype CRF35-AD.&#x0D; Conclusions:&#x0D; The present study reports updates on the mutations related to RT resistance in Iranian HIV patients receiving treatment, show that 20% of the samples had a high-level of resistance to Lamivudine, and Emtricitabine which should be confirmed for further antiretroviral (AVR) regimens for HIV infected patients. Also, two new mutations related to resistance to Nevirapine, Doravirine, Zidovudine, and Stavudine were introduced in this investigation.&#x0D; The present results could be used as predictive information on the response to anti-RT, and also highlight the importance of considering the periodic monitoring of HIV resistance test in HIV infected patients.

Immunogenetic features of HIV-infection and allergy comorbidity

Today, the comorbidity of infection caused by the human immunodeficiency virus (HIV) is an important problem due to the complexity of the selection of the optimal antiretroviral therapy and the diagnosing of associated pathological conditions. The study of the comorbidity of HIV-infection and allergy is an important area of research. This article presents a literature review on different types of comorbidity. Special attention is paid to the development of allergic reactions to antiretroviral drugs. The presence of an allergic reaction in a patient can cause low adherence to therapy and subsequent development of HIV resistance to the treatment. The review provides information on the possible causes of the development of hypersensitivity in HIV-infected patients. The data on the development of hypersensitivity reactions in response to treatment with the main classes of antiretroviral drugs (nucleoside and non-nucleoside reverse transcriptase inhibitors, synthesis inhibitors, protease inhibitors, integrase inhibitors, cysteine-cysteine chemokine receptor 5 inhibitors) are presented. The most common allergic reactions to these drug classes are itching and rash, as well as increasing hepatic transaminase levels and cough. The existing scientific data on allergic reactions to drugs prescribed for other concurrent conditions (tuberculosis, fungal diseases) is also considered. The examples of studies reflecting the relevance of using immunogenetic and molecular genetic approaches in the study of comorbidity of HIV-infection and allergy are given. The identification of immunogenetic markers of the development of the hypersensitivity to therapy will optimize the diagnostic and treatment algorithms, especially in complex comorbid conditions.

Анализ частоты формирования мутаций резистентности ВИЧ, ассоциированных с устойчивостью к антиретровирусным препаратам

Актуальность. В Украине проводится широкомасштабная антиретровирусная терапия (АРТ) больных ВИЧ-инфекцией. Необходимо постоянное наблюдение за развитием устойчивости ВИЧ к антиретровирусным препаратам (АРВП). Цель: проанализировать влияние продолжительности АРТ, возраста и пола пациентов на частоту формирования мутаций резистентности (МР) ВИЧ к АРВП разных классов. Материал и методы. Исследовали образцы плазмы крови ВИЧ-инфицированных пациентов с вирусологической неэффективностью АРТ. Секвенирование генома ВИЧ проводили на тест-системах ViroSeqTM Genotyping System v.2.1 (Celera Diagnostics, США) согласно инструкции производителя. Результаты. Достоверно чаще (р ≤ 0,05) МР ВИЧ к АРВП выявлялись у ВИЧ-инфицированных мужчин (59,70 %), чем у женщин (40,3 %). Установлено, что в 59,9 % случаев вирусологическая неэффективность АРТ была обусловлена формированием МР ВИЧ хотя бы к одному из АРВП. Среди МР ВИЧ к ненуклеозидным ингибиторам обратной транскриптазы наиболее распространенными были G190S (75,8 %); K101E (72,7%); Y181C (68,1 %); K103N (38,8 %); среди МР к нуклеозидным ингибиторам обратной транскриптазы преобладали: M184V (69 %), K65R (61 %), D67N (20 %). МР ВИЧ к ингибитору протеазы встречались редко. Выводы. Показано, что продолжительность АРТ и возраст пациентов существенного влияния на устойчивость ВИЧ к АРВП не оказывали. Решающее значение имел генетический барьер АРВП: на фоне приема препаратов с низким генетическим барьером частота выявления МР ВИЧ составляла 5,3 %; прием препаратов с высоким генетическим барьером сопровождался формированием МР ВИЧ значительно реже — в 1,1 % случаев. Доказано, что биоповеденческие особенности пациентов-мужчин являются фактором, ассоциирующимся с повышенным риском формирования МР ВИЧ к АРВП.

Stem Cell Therapy and Its Significance in HIV Infection.

Human immunodeficiency virus (HIV) infection is a major global public health issue. Despite this, the only treatment available in mainstay is antiretroviral therapy. This treatment is not curative, it needs to be used lifelong, and there are many issues with compliance and side effects. In recent years, stem cell therapy has shown promising results in HIV management, and it can have a major impact on the future of HIV treatment and prevention. The idea behind anti-HIV hematopoietic stem/progenitor cell (HSPC)-directed gene therapy is to genetically engineer patient-derived (autologous) HSPC to acquire an inherent resistance to HIV infection. Multiple stem-cell-based gene therapy strategies have been suggested that may infer HIV resistance including anti-HIV gene reagents and gene combinatorial strategies giving rise to anti-HIV gene-modified HSPCs. Such stem cells can hamper HIV progression in the body by interrupting key stages of HIV proliferation: viral entry, viral integration, HIV gene expression, etc.Hematopoietic stem cells (HSCs) may also protect leukocytes from being infected. Additionally, genetically engineered HSCs have the ability to continuously produce protected immune cells by prolonged self-renewal that can attack the HIV virus. Therefore, a successful treatment strategy has the potential to control the infection at a steady state and eradicate HIV from patients. This will allow for a potential future benefit with stem cell therapy in HIV treatment.

RHIVDB: A Freely Accessible Database of HIV Amino Acid Sequences and Clinical Data of Infected Patients.

Human immunodeficiency virus (HIV) infection remains one of the most severe problems for humanity, particularly due to the development of HIV resistance. To evaluate an association between viral sequence data and drug combinations and to estimate an effect of a particular drug combination on the treatment results, collection of the most representative drug combinations used to cure HIV and the biological data on amino acid sequences of HIV proteins is essential. We have created a new, freely available web database containing 1,651 amino acid sequences of HIV structural proteins [reverse transcriptase (RT), protease (PR), integrase (IN), and envelope protein (ENV)], treatment history information, and CD4+ cell count and viral load data available by the user’s query. Additionally, the biological data on new HIV sequences and treatment data can be stored in the database by any user followed by an expert’s verification. The database is available on the web at http://www.way2drug.com/rhivdb.

Distribution of CCR5 Δ32 HIV-1 resistance allele frequency at Zanjan province in Iran

Introduction: The CC chemokine receptor 5 (CCR5) is known as the main co-receptor in human immunodeficiency virus (HIV) infection. Accumulating evidence verified 32bp deletion in both alleles of CCR5 provides natural resistance to HIV infection. Accordingly, recent therapeutic approaches are based on gene and cell therapies by inducing this resistance. Allogeneic transplantation of stem cells with CCR5Δ32 homozygous to HIV infected people has been considered as an efficient strategy. Objectives: The aim of this study was to determine CCR5 Δ32 mutation frequency in healthy and HIV-infected individuals in Zanjan province, in Iran and also detecting appropriate candidate for future therapeutic approaches. Patients and Methods: In this study, blood samples were collected from 102 HIV infected patients and 204 healthy controls in ethylene diamine tetra-acetic acid (EDTA) pre-coated tubes. DNA extraction was performed and analyzed for CCR5Δ32 mutation by GAP-PCR in both groups and followed by 2% gel agarose electrophoresis. The Δ32 genotype frequency was statistically determined. Results: Our finding demonstrated that 3 HIV infected patients displayed CCR5 mutation, while 204 healthy controls showed one CCR5 Δ32/Δ32 homozygote mutation. We observed that Δ32 mutation frequency is 0.82% in Zanjan province (χ2 =47.58, P&lt;0.001). Conclusion: Reduction in CCR5 mutation frequency as well as the other polymorphisms related to HIV resistance, can lead to the development of HIV infection epidemiology. Migration, natural selection and genetic admixture can elucidate various distribution of Δ32 allele frequency in different populations, like as north Europeans that reduce gradually to south. The result of this study can facilitate the presentation of suitable Δ32 donors to HIV infected patients in therapeutic approaches.

Recent developments in CCR5 regulation for HIV cure.

Acquired immunodeficiency syndrome (AIDS) has affected millions of people worldwide. The human immunodeficiency virus (HIV) which infects T cells by using CD4 as its main receptor. Currently different treatments are available against HIV infection which can improve life expectancy of the patient but still it remains incurable. CCR5, which is also required as a co-receptor by majority of HIV strains for entry into the target cells, is now being targeted for gene therapy to develop HIV resistance in patients. In this review, we discuss different strategies that are being adapted for CCR5-gene disruption in CD4+ T cells and in hematopoietic stem cells (HSCs) to generate a HIV-resistant immune system in infected individuals. If CCR5 gene that can shape HIV-resistant T cells, it will aim in new approaches in clinical trials. But these techniques have certain weaknesses and disadvantages, and will need to be paired with other strategies to form a full HIV remedy. There is also a need to establish methods to help deter HIV re-emergence following targeted CCR5 therapy. But ultimately, this brought us a better knowledge of the road to HIV treatment.

Antiviral activity of extracts of basidiomycetes and humic compounds substances against Human Immunodeficiency Virus (Retroviridae: Orthoretrovirinae: Lentivirus: Human immunodeficiency virus 1) and Herpes Simplex Virus (Herpesviridae: Simplexvirus: Human alphaherpesvirus 1)

One of the most urgent problem of modern medicine is the fight against the disease caused bythe Human Immunodeficiency Virus (HIV) - HIV infection. The chemical compounds have improved the situationfor infected people, but they are toxic, disrupt the metabolism and cannot eliminate the integrated virus from thebody. The emergence of resistant HIV strains makes these treatments ineffective. Often, the death of HIV-infectedpeople occurs as a result of the development of opportunistic infections caused by viruses of the Herpesviridaefamily. Therefore, the search for new therapeutic and preventive drugs that are less toxic and active against severalviruses at the same time is relevant. Basidiomycetes, higher fungi, are a source of medicinal compounds that haveantimicrobial properties, as well as antiviral ones. Humic compounds (HS) of various nature also have antiviralactivity.The aim of the study was to obtain nontoxic compounds from the basidiomycete Inonotus obliquus and humiccompounds from brown coals and to test their activity against viruses that are pathogenic to humans: HIV andHerpes Simplex Virus (HSV). The antiviral activity of melanin extracts obtained from the culture of the chaga fungusInonotus obliquus and HS from the brown coal of the Kansko-Achinsk Deposit was studied using a model of MT-4lymphoblastoid cells infected with HIV type 1 (HIV-1) strains and a monolayer culture of Vero cells infected withHSV type 1 (HSV-1) using virological and statistical research methods. It was found that all the studied compounds did not have a cytotoxic effect on cells at aconcentration of 100 mcg/ml. It was shown that extracts of basidiomycetes and HS have antiviral activity againstHIV-1 and HSV-1. EC50 (50%-effective concentration) for HIV-1 was 3.7-5.0 mcg/ml, selectivity index 28-35.Antiherpetic activity was detected at a dose of 50-100 mcg/ml. The antiviral effectiveness of melanin compoundswas established both in the «preventive» (2 hours before cell infection) and in the «therapeutic» regimen of drugadministration, both for HIV-1 and HSV-1. The presence of antiviral activity of melanin and HS in relation to theRNA-containing HIV-1 virus and DNA-containing HSV-1 virus in our study coincides with the results of a number ofauthors in relation to influenza viruses, herpes virus, HIV, hepatitis B virus, Coxsackievirus, smallpox vaccine virus,which suggests that the type of nucleic acid in the virus does not play a fundamental role in the antiviral action ofthese drugs. It is also clear that HS is effective against both enveloped and non-enveloped viruses. In general, it can be concluded that melanin and humic compounds are characterized by low toxicityin the presence of both virucidal and antiviral activity. This allows us to consider the studied compounds as thebasis for creating safe medicines that are effective against pathogens of various viral infections.

Evaluating the impact of antiretroviral and antiseizure medication interactions on treatment effectiveness among outpatient clinic attendees with HIV in Zambia.

Interactions between enzyme-inducing anti-seizure medications (EI-ASMs) and antiretroviral drugs (ARVs) can lead to decreased ARV levels and may increase the likelihood of viral resistance. We conducted a study to determine if co-usage of ARVs and EI-ASMs is associated with ARV-resistant human immunodeficiency virus (HIV) among people living with HIV in Zambia. Eligible participants were ≥18years of age and concurrently taking ASMs and ARVs for at least 1month of the prior 6-month period. Data were obtained regarding medication and HIV history. CD4 counts, plasma viral loads (pVLs), and HIV genotype and resistance profile in participants with a pVL >1000copies/mL were obtained. Pearson's test of independence was used to determine whether treatment with EI-ASM was associated with pVL >1000/mL copies. Of 50 participants, 41 (82%) were taking carbamazepine (37 on monotherapy), and all had stable regimens in the prior 6months. Among the 13 ARV regimens used, 68% had a tenofovir/lamivudine backbone. The majority (94%) were on a stable ARV regimen for >6months. Median CD4 nadir was 205 cells/mm3 (interquartile range [IQR] 88-389), and 60% of participants had commenced ARV treatment before advanced disease occurred. Mean CD4 count at enrollment was 464cells/mm3 (SD 226.3). Seven participants (14%) had a CD4 count <200cells/mm3 . Four (8%) had a pVL >1000copies/mL; all were on carbamazepine. Three participants with elevated pVL had a CD4 count <200cells/mm3 . None had documented adherence concerns by providers; however, two had events concerning for clinical failure. HIV genotype testing showed mutations in three participants. Carbamazepine was not found to correlate with elevated pVL (P=.58). EI-ASMs are commonly used in sub-Saharan Africa. Despite concurrent use of EI-ASMs and ARVs, the majority of participants showed CD4 counts >200 cells/mm3 and were virally suppressed. Carbamazepine was not associated with an increased risk of virological failure or ARV-resistant HIV.

Resistance to human immunodeficiency virus infection: a rare but neglected state.

The natural history of human immunodeficiency virus (HIV) infection is well understood. In most individuals sexually exposed to HIV, the risk of becoming infected depends on the viral load and on sexual practices and gender. However, a low percentage of individuals who practice frequent unprotected sexual intercourse with HIV-infected partners remain uninfected. Although the systematic study of these individuals has made it possible to identify HIV resistance factors including protective genetic patterns, such epidemiological situations remain paradoxical and not fully understood. In vitro experiments have demonstrated that peripheral blood mononuclear cells (PBMCs) from HIV-free, unexposed blood donors are not equally susceptible to HIV infection; in addition, PBMCs from highly exposed seronegative individuals are generally resistant to infection by primary HIV clinical isolates. We review the literature on permissiveness of PBMCs from healthy blood donors and uninfected hyperexposed individuals to sustained infection and replication of HIV-1 in vitro. In addition, we focus on recent evidence indicating that the gut microbiota may either contribute to natural resistance to or delay replication of HIV infected individuals.

Prevalence and molecular characterization of hepatitis B virus infection in HIV-infected children in Senegal

Background and aimsSub-Saharan Africa (SSA) is the region with the most patients co-infected with the human immunodeficiency virus (HIV) and the hepatitis B virus (HBV) worldwide. However, few studies have focused on SSA children who are at a higher risk of developing a chronic infection than adults. Furthermore, children on first-line antiretroviral therapy (ART) including low genetic barrier drugs may develop both HBV and HIV resistance mutations. The aim of this work was to document HIV-HBV co-infection and to characterize the HBV isolates in children in Senegal. MethodsThis is a retrospective study of 613 children infected with HIV on ART or not. Dried blood spot (DBS) specimens were used to detect hepatitis B surface antigen (HBsAg) with a rapid diagnostic test (RDT). Confirmation of HBsAg status and hepatitis B e antigen (HBeAg) detection was performed on an automated platform using the chemiluminescence assay technology. HBV viral DNA was quantified by real-time polymerase chain reaction (PCR) and the preS1/preS2/HBsAg region was genotyped by nested PCR followed by sequencing using the Sanger technique. ResultsThe prevalence of HIV-HBV co-infection was 4.1% (25/613). The median age of co-infected children was 13 years (2 years–16 years) and 40% (10/25) were girls. Almost all 19/20 (95%) were infected with HIV-1 and 79% (19/24) were treated with 3TC-based triple combination ART. The median duration of time on ART was 15 months (3 months–80 months). More than half of the children 53% (9/17) were experiencing HIV virologic failure and 75% (6/8) had at least one HIV-related resistance-associated mutation (RAM). Of the six children with resistance, none of the three administered treatments were effective on HIV. Of the 25 co-infected children, 82% (18/22) were HBeAg-positive, while the median HBV viral load (VL) was 6.20 log10 IU/mL (24/25 patients), and 62,5% (10/16) of the children had a persistent HBV viremia. Combination of ART was the only factor associated with HBV viremia persistence. Amplification was successful in 15 out of 16 patients (rate of 94%), and the ensuing phylogenetic analysis revealed that eight strains (53%) belonged to genotype A and seven (47%) to genotype E. HBV-related 3TC RAMs were uncovered in 20% of these patients (3/15). HBsAg escape mutations were found in 20% of the children (3/15). ConclusionsOur results showed a high level of drug resistance mutations to both HIV and HBV, a significant level of HBsAg escape mutations, HBV DNA persistence and HIV virologic failure in co-infected children in Senegal. The HBV genotypes found were A and E.

Anti-HIV/SIV activity of icariin and its metabolite anhydroicaritin mainly involve reverse transcriptase

AIDS, a serious fatal disease caused by the human immunodeficiency virus (HIV), is an epidemic disease for which no effective vaccine has been established. The current therapeutic interventions for AIDS have limited efficacy because they are unable to clear HIV infections and the continuous occurrence of resistant HIV strains. Therefore, the exploitation of new drugs to prevent the spread of AIDS remains a high priority. In this study, the effects of icariin and its metabolite anhydroicaritin on SIV/HIV replication were investigated. In CEM × 174 cells and PBMC cells, both icariin and anhydroicaritin can significantly inhibit HIV-1 or SIVmac251 replication. Furthermore, molecular docking studies revealed that icariin and anhydroicaritin can act on both HIV reverse transcriptase and protease but could not bind to integrase. Reverse transcriptase and protease inhibition biological assays showed that both icariin and anhydroicaritin could significantly inhibit only HIV reverse transcriptase. In summary, the two compounds can significantly inhibit HIV/SIV in vitro and their targets may be mainly involved with HIV reverse transcriptase.

Retrospective analysis of HIV-1 drug resistance mutations in Suzhou, China from 2009 to 2014.

In this study, we investigated drug resistance levels in human immunodeficiency virus (HIV)-1-infected patients in Suzhou by retrospectively analyzing this property and the characteristics of circulating HIV-1 strains collected from 2009 to 2014. A total of 261 HIV-1-positive plasma samples, confirmed by the Suzhou CDC, were collected and evaluated to detect HIV-1 drug resistance genotypes using an in-house method. The pol gene fragment was amplified, and its nucleic acid sequence was determined by Sanger sequencing. Drug resistance mutations were then analyzed using the Stanford University HIV resistance database ( https://hivdb.stanford.edu ). A total of 216 pol gene fragments were amplified and sequenced with 16.7% (36/216) of sequences revealing these mutations. The drug resistance rates of protease, nucleoside reverse transcriptase, and non-nucleoside reverse transcriptase inhibitors (NNRTIs) were 4/36 (11.1%), 2/36 (5.6%), and 30/36 (83.3%), respectively. Five surveillance drug resistance mutations were found in 36 sequences, of which, three were found among specimens of men who have sex with men. Potential low-level resistance accounted for 33% of amino acid mutations associated with NNRTIs. Two of the mutations, M230L and L100I, which confer a high level of resistance efavirenz (EFV) and nevirapine (NVP) used as NNRTIs for first-line antiretroviral therapy (ART), were detected in this study. Therefore, when HIV-1 patients in Suzhou are administered fist-line ART, much attention should be paid to the status of these mutations that cause resistance to EVP, EFV, and NVP.

Exploring the Mechanisms of Drug Resistance with a 3D Molecular Model of HIV Protease

Human immunodeficiency virus (HIV) affects 37 million people worldwide. HIV causes Acquired Immunodeficiency Syndrome (AIDS) by impairing the immune functions in the human body and is transmitted through contact of body fluid. HIV attacks the body’s immune system, specifically CD4 T cells which help the immune system fight off infection. Antiretroviral therapy (ART) has prolonged the life expectancy of those under the treatment process. ART is a combination of antiretroviral drugs that keep the virus from replicating. The drug combination “cocktail” combines the power of multiple drugs to block multiple targets in HIV replication. HIV‐1 protease is an essential enzyme for the life cycle of HIV. Therefore, HIV‐1 protease is an important target used in antiretroviral therapy. However, under the selective pressure of protease inhibitors, mutations may occur at the active site, crippling inhibitor binding and leading to drug resistance. Umass6 is an analog of the HIV protease inhibitor, duranovir, with a bulky P1′ moiety that allows enhanced overall van der Waals interactions at the active site. Here, we design a 3D model of the drug resistant HIV protease mutant I50V bound to UMass6 using Jmol based on the crystal structure described by Gordon J. Lockbaum and colleagues (1). HIV protease is a homodimer with the active site located in the interface between the subunits. Our model highlights the location of the I50V mutation within the active site and the resulting structural changes that cause the loss of inhibitor potency. Our 3D model also highlights the critical residues involved in inhibitor binding and the catalytic residue, D25, within the active site. Designing 3D model exposes students to protein structure, mutations, and tools for understanding drug resistance.Support or Funding InformationThis work is supported by NSF‐DUE1725940 and NSF‐HRD1623340.