Baltimore oral epidemiology, disease effects, and HIV evaluation study (BEEHIVE) study protocol: a prospective cohort study.

BACKGROUND: As antiretroviral therapy has become widely available and highly effective, HIV has evolved to a manageable, chronic disease. Despite this health advancement, people living with HIV (PLWH) are at an increased risk for age-related non-communicable diseases (NCDs) compared to HIV-uninfected individuals. Similarly, PLWH are at an increased risk for selected oral diseases. PLWH with a history of injecting drugs experience an even greater burden of disease than their counterparts. The overall objective of the Baltimore Oral Epidemiology, Disease Effects, and HIV Evaluation (BEEHIVE) study is to determine the combined effects of HIV infection and NCDs on oral health status. The specific aims of the study are to: (1) determine to what extent HIV status influences access to and utilization of oral health care services; (2) determine to what extent HIV status affects self-reported and clinical oral health status; (3) determine to what extent HIV status influences the progression of periodontitis; and (4) determine to what extent HIV status impacts the periodontitis-associated oral microbiome signature. METHODS: The BEEHIVE study uses a prospective cohort study design to collect data from participants at baseline and at a 24-month follow-up visit. Data are collected through questionnaire assessments, clinical examinations, and evaluation of oral microbiological samples to determine the drivers of oral disease among a high-risk population of PLWH with a history of injection drug use and prevalent comorbid NCDs. The established AIDS Linked to the Intravenous Experience (ALIVE) cohort serves as the source of participants for the BEEHIVE Study. DISCUSSION: Upon completion of the BEEHIVE study, the knowledge gained will be important in informing future clinical and preventive interventions that can be implemented into medical and dental practice to ultimately help eliminate long-standing oral health inequities that PLWH experience.

Predictive model and risk analysis for coronary heart disease in people living with HIV using machine learning.

OBJECTIVE: This study aimed to construct a coronary heart disease (CHD) risk-prediction model in people living with human immunodeficiency virus (PLHIV) with the help of machine learning (ML) per electronic medical records (EMRs). METHODS: Sixty-one medical characteristics (including demography information, laboratory measurements, and complicating disease) readily available from EMRs were retained for clinical analysis. These characteristics further aided the development of prediction models by using seven ML algorithms [light gradient-boosting machine (LightGBM), support vector machine (SVM), eXtreme gradient boosting (XGBoost), adaptive boosting (AdaBoost), decision tree, multilayer perceptron (MLP), and logistic regression]. The performance of this model was assessed using the area under the receiver operating characteristic curve (AUC). Shapley additive explanation (SHAP) was further applied to interpret the findings of the best-performing model. RESULTS: The LightGBM model exhibited the highest AUC (0.849; 95% CI, 0.814-0.883). Additionally, the SHAP plot per the LightGBM depicted that age, heart failure, hypertension, glucose, serum creatinine, indirect bilirubin, serum uric acid, and amylase can help identify PLHIV who were at a high or low risk of developing CHD. CONCLUSION: This study developed a CHD risk prediction model for PLHIV utilizing ML techniques and EMR data. The LightGBM model exhibited improved comprehensive performance and thus had higher reliability in assessing the risk predictors of CHD. Hence, it can potentially facilitate the development of clinical management techniques for PLHIV care in the era of EMRs.

Prevalence and Epidemiological Characteristics of Anogenital Warts Among Recently Diagnosed HIV-Positive Women on Antiretroviral Therapy in Lagos, Nigeria.

Background Anogenital warts (AGWs) are a prevalent condition resulting from human papillomavirus (HPV) infection, which is the most frequently encountered sexually transmitted infection (STI) on a global scale. Women who are HIV-positive experience a disproportionately high burden of AGWs compared to other populations. It is imperative to comprehend the epidemiological factors linked to the disease within this particular at-risk population. Objectives The objective of the study was to ascertain the prevalence of AGWs and its demographic and socio-biological epidemiological features among recently diagnosed HIV-positive women (HPW) in Lagos, Nigeria. Materials and methods The research was a descriptive cross-sectional study conducted among a sample of 420 recently diagnosed HPW. The study was conducted at the HIV clinic of a tertiary health institution located in Lagos, Nigeria. The participants clinically diagnosed with AGWs were classified as the study group, while individuals without AGWs were classified as the comparison group. Interviewer-administered pretested questionnaires were utilized to gather pertinent demographic and socio-biological epidemiological data from the participants involved in the study. The data were analyzed using IBM SPSS Statistics for Windows, Version 23.0 (Released 2015; IBM Corp., Armonk, New York, USA). Results The prevalence of AGWs among recently diagnosed HPW was found to be 8.5% (34/402). These warts were frequently observed on the vulvar labia (35.3%, 12/34), vaginal walls (14.7%, 5/34), and perianal region (14.7%, 5/34). It is worth noting that over a third of cases (35.3%, 12/34) involved multiple areas within the anogenital region. The diagnosis of AGWs was found to have significant associations with occupation (p=0.005), marital status (p<0.001), and educational status (p=0.028). The majority of HPW diagnosed with AGWs were unemployed (32.4%, 11/34), single (47.1%, 16/34), and did not have tertiary education (94.1%, 32/34). The utilization of oral contraceptive pills (OCPs), smoking, low CD4 count, and high viral load were the significant socio-biological factors associated with the diagnosis of AGWs (p<0.001, respectively). Conclusion The study found that the prevalence of AGW among HPW was 8.5% (34/402). Several epidemiological factors, including occupation, marital status, education, CD4 count, viral load, history of OCP use, and smoking, were found to be significantly associated with the diagnosis of AGW. There is a need to conduct more comprehensive studies to thoroughly assess the impact of these epidemiological factors.

Serum gonadal hormones levels and hypogonadism in ART naïve newly diagnosed HIV infected adult males in Mwanza, Tanzania.

BACKGROUND: Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) is an endemic chronic disease which is characterized with progressive depletion of CD4 T cells and increased susceptibility to opportunistic infections. Previous studies have associated HIV infection with increased hypogonadism. However, the prevalence of hypogonadism remained poorly defined and widely ranging in various studies. This study aims to evaluate the serum gonadal hormonal levels and hypogonadism in antiretroviral therapy (ART) naïve newly diagnosed HIV infected-males in Mwanza, Tanzania. METHODS: This was a comparison study involving 81 ART naïve newly diagnosed HIV-infected adult males as study group and 81 apparently healthy HIV-negative males as comparison group. The participants in the study group and comparison group were matched by body mass index and age. Serum hormones [Total testosterone (TT), follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E) were estimated. Serum testosterone < 300 ng/dl, or testosterone > 300 ng/dl with high LH and FSH (compensatory hypogonadism) were taken as markers of hypogonadism. Data were analyzed using STATA version 15. RESULTS: The median serum testosterone level among ART naïve newly diagnosed HIV-infected adult males was significantly lower as compared to their comparison group (447 [259-534] versus 517 [396-605]; p = 0.0074) and shown to decrease with decreasing CD4 level. The median [IQR] serum FSH level among ART naïve newly diagnosed HIV-infected adult males was significantly higher than among their comparison group (3.8 [2.1-6.5] versus 2.6 [1.8-4.2]; p = 0.0086). The differences in serum LH and Estradiol were not statistically significant. Furthermore, the proportion of hypogonadism was significantly higher among ART naïve newly diagnosed HIV-infected adult males than in their comparison group (37.0% [30/81] versus 14.8% [12/81]; p = 0.0006). Out of these 30, 24 HIV-infected males had secondary hypogonadism, one had primary, and the remaining five had compensatory hypogonadism. CONCLUSION: Serum testosterone was lower and follicle stimulating hormone was higher among ART naïve HIV-infected males as compared to the HIV negative controls. Hypogonadism, mainly secondary, is common endocrine abnormality among ART naïve HIV-infected male patients in this study. HIV is associated with variations in gonadal hormones which may lead to sexual dysfunction in infected individuals.

Secondary hemophagocytic syndrome in an acquired immunodeficiency syndrome and Alpha-thalassemia patient infected with Talaromyces marneffei: A case report and literature review.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease characterized by a hyperinflammatory syndrome and impairment of multiple organ systems. Talaromycosis marneffei (TSM) is an opportunistic infection mostly found in immunosuppressed populations, such as those with acquired immunodeficiency syndrome (AIDS), and is prevalent in southern China. However, HLH secondary to TSM is extremely rare and has only been reported in isolated cases. A 30-year-old patient with recurrent high fever and progressive cytopenia was diagnosed with HLH secondary to disseminated TSM with AIDS and Alpha-thalassemia. The patient remained in sustained remission without recurrence after effective treatment with antifungals and glucocorticoids.

HIV seroconversion and associated factors among seronegative pregnant women attending ANC in Ethiopia: an institution-based cross-sectional study.

Background: In countries with limited resources, including Ethiopia, HIV is diagnosed using a rapid serological test, which does not detect the infection during the window period. Pregnant women who test negative for HIV on the first test may seroconvert throughout pregnancy. Women who are seroconverted during pregnancy may not have received interventions, as they are considered HIV-negative unless they are retested for HIV at the end of their pregnancy. Due to limited data on HIV seroconversion, this study aimed to measure the extent of HIV seroconversion and to identify associated factors among seronegative pregnant women attending ANC in Ethiopia. Methods: Institution-based cross-sectional study was conducted among HIV-negative pregnant women attending the ANC in Ethiopia between June and July 2020. Socio-demographic, clinical, and behavioral data were collected through face-to-face questionnaires and participants' records review. HIV retesting was performed to determine the current HIV status of pregnant women. The data collected were entered into Epi data version 4.4.1 and were exported and analyzed by SPSS version 25. A p-value < 0.25 in the bivariate analysis was entered into multivariable logistic regression analysis and a p-value of < 0.05 was considered statistically significant. Result: Of the 494 pregnant women who tested negative for HIV on their first ANC test, six (1.2%) tested positive on repeat testing. Upon multivariable logistic regression, pregnant women who have had a reported history of sexually transmitted infections [AOR = 7.98; 95% CI (1.21, 52.82)], participants' partners reported travel history for work frequently [AOR = 6.00; 95% CI (1.09, 32.99)], and sexually abused pregnant women [AOR = 7.82; 95% CI (1.194, 51.24)] were significantly associated with HIV seroconversion. Conclusion: The seroconversion rate in this study indicates that pregnant women who are HIV-negative in early pregnancy are at an ongoing risk of seroconversion throughout their pregnancy. Thus, this study highlights the benefit of a repeat HIV testing strategy in late pregnancy, particularly when the risk of seroconversion or new infection cannot be convincingly excluded. Therefore, repeated testing of HIV-negative pregnant women in late pregnancy provides an opportunity to detect seroconverted pregnant women to enable the timely use of ART to prevent mother-to-child transmission of HIV infection.

Prevalence of Diagnosed and Undiagnosed Depression Among US Adults with Human Immunodeficiency Virus: Data from the Medical Monitoring Project.

People with human immunodeficiency virus (PWH) are disproportionately affected by depression, but the recent national estimates for US PWH encompassing both current symptoms and clinical diagnoses to assess missed diagnoses and lack of symptom remission are lacking. We used data from CDC's Medical Monitoring Project (MMP) to report nationally representative estimates of diagnosed and undiagnosed depression among US adult PWH. During June 2021 to May 2022, MMP collected interview data on symptoms consistent with major or other depression and depression diagnoses from medical records of 3928 PWH. We report weighted percentages and prevalence ratios (PRs) to quantify differences between groups on key social and health factors. Overall, 34% of PWH experienced any depression (diagnosis or Patient Health Questionnaire-8); of these, 26% had symptoms but no diagnosis (undiagnosed depression), 19% had both diagnosis and symptoms, and 55% had a diagnosis without symptoms. Among those with depression, persons with a disability (PR: 1.52) and food insecurity (PR: 1.67) were more likely to be undiagnosed. Unemployed persons (PR: 1.62), those experiencing a disability (PR: 2.78), food insecurity (PR: 1.46), or discrimination in human immunodeficiency virus (HIV) care (PR: 1.71) were more likely to have diagnosed depression with symptoms. Those with symptoms (undiagnosed or diagnosed) were less likely to be antiretroviral therapy (ART) dose adherent (PR: 0.88; PR: 0.73) or have sustained viral suppression (PR: 0.62; PR: 0.91) and were more likely to have unmet needs for mental health services (PR: 2.38, PR: 2.03). One-third of PWH experienced depression, of whom nearly half were undiagnosed or still experiencing clinically relevant symptoms. Expanding screening and effective treatment for depression could improve quality of life and HIV outcomes.

Spatiotemporal binding of cyclophilin A and CPSF6 to capsid regulates HIV-1 nuclear entry and integration.

Human immunodeficiency virus type 1 (HIV-1) capsid, which is the target of the antiviral lenacapavir, protects the viral genome and binds multiple host proteins to influence intracellular trafficking, nuclear import, and integration. Previously, we showed that capsid binding to cleavage and polyadenylation specificity factor 6 (CPSF6) in the cytoplasm is competitively inhibited by cyclophilin A (CypA) binding and regulates capsid trafficking, nuclear import, and infection. Here we determined that a capsid mutant with increased CypA binding affinity had significantly reduced nuclear entry and mislocalized integration. However, disruption of CypA binding to the mutant capsid restored nuclear entry, integration, and infection in a CPSF6-dependent manner. Furthermore, relocalization of CypA expression from the cell cytoplasm to the nucleus failed to restore mutant HIV-1 infection. Our results clarify that sequential binding of CypA and CPSF6 to HIV-1 capsid is required for optimal nuclear entry and integration targeting, informing antiretroviral therapies that contain lenacapavir.

Microglial- neuronal crosstalk in chronic viral infection through mTOR, SPP1/OPN and inflammasome pathway signaling.

HIV-infection of microglia and macrophages (MMs) induces neuronal injury and chronic release of inflammatory stimuli through direct and indirect molecular pathways. A large percentage of people with HIV-associated neurologic and psychiatric co-morbidities have high levels of circulating inflammatory molecules. Microglia, given their susceptibility to HIV infection and long-lived nature, are reservoirs for persistent infection. MMs and neurons possess the molecular machinery to detect pathogen nucleic acids and proteins to activate innate immune signals. Full activation of inflammasome assembly and expression of IL-1ß requires a priming event and a second signal. Many studies have demonstrated that HIV infection alone can activate inflammasome activity. Interestingly, secreted phosphoprotein-1 (SPP1/OPN) expression is highly upregulated in the CNS of people infected with HIV and neurologic dysfunction. Interestingly, all evidence thus far suggests a protective function of SPP1 signaling through mammalian target of rapamycin (mTORC1/2) pathway function to counter HIV-neuronal injury. Moreover, HIV-infected mice knocked down for SPP1 show by neuroimaging, increased neuroinflammation compared to controls. This suggests that SPP1 uses unique regulatory mechanisms to control the level of inflammatory signaling. In this mini review, we discuss the known and yet-to-be discovered biological links between SPP1-mediated stimulation of mTOR and inflammasome activity. Additional new mechanistic insights from studies in relevant experimental models will provide a greater understanding of crosstalk between microglia and neurons in the regulation of CNS homeostasis.

Unusual presentation of PD-1 inhibitors in people living with HIV with advanced gastric cancer: Case report.

This paper seeks to determine the effect of combination anti-PD-1 and antiretroviral therapy (ART) on people living with HIV (PLWH) with advanced gastric cancer. In our case, a PLWH with recurrent locally advanced gastric cancer was treated with anti-PD-1 inhibitor and ART. A significant reduction in tumor lesions (as demonstrated by contrast-enhanced CT imaging) and a better quality of life were achieved following treatment. There have been limited studies on the treatment of PLWH with advanced gastric cancer. Chemotherapy is most often used, however, with unsatisfactory outcomes. to date, there have been no published reports on the use of PD-1 inhibitors in PLWH with advanced gastric cancer. Our report provides a valuable reference for future management of such patients.

Label-free and portable detection of HIV-DNA by a handheld luminometer.

BACKGROUND: The human immunodeficiency virus (HIV) remains a major worldwide health problem. Nowadays, many methods have been developed for quantitative detecting human immunodeficiency virus DNA (HIV-DNA), such as fluorescence and colorimetry. However, these methods still have the disadvantages of being expensive and requiring professional technicians. Early diagnosis of pathogens is increasingly dependent on portable instruments and simple point-of-care testing (POCT). Therefore, it is meaningful and necessary to develop portable and cheap methods for detecting disease markers. RESULTS: In this work, a label-free chemiluminescence (CL) method was developed for detecting HIV-DNA via a handheld luminometer. To achieve label-free target detection, the CL catalyst, G-triplex-hemin DNAzyme (G3-hemin DNAzyme), was in-situ assembled in the presence of HIV-DNA. For improving sensitivity, HIV-DNA induced the cyclic strand displacement reaction (SDR), which can form three G3-hemin DNAzymes in one cycle. So, the chemiluminescence reaction between luminol and H2O2 was highly effectively catalyzed, and the CL intensity was linearly related with the concentration of HIV-DNA in the range of 0.05-10 nM with a detection limit of 29.0 pM. Due to the high specificity of hairpin DNA, single-base mismatch can be discriminated, which ensured the specific detection of HIV-DNA. SIGNIFICANCE: In-situ formation of G3-hemin DNAzyme led to label-free and selective detection without complex synthesis and functionalization. Therefore, it offers a cheap, selective, sensitive and portable method for detecting disease-related genes, which is promising for POCT of clinical diagnosis in resource-limited settings.

Glycan-Imprinted Nanoparticle as Artificial Neutralizing Antibody for Efficient HIV-1 Recognition and Inhibition.

The HIV-1 envelope is a heavily glycosylated class 1 trimeric fusion protein responsible for viral entry into CD4+ immune cells. Developing neutralizing antibodies against the specific envelope glycans is an alternative method for antiviral therapies. This work presents the first-ever development and characterization of artificial neutralizing antibodies using molecular imprinting technology to recognize and bind to the envelope protein of HIV-1. The prepared envelope glycan-imprinted nanoparticles (GINPs) can successfully prevent HIV-1 from infecting target cells by shielding the glycans on the envelope protein. In vitro experiments showed that GINPs have strong affinity toward HIV-1 (Kd = 36.7 ± 2.2 nM) and possess high anti-interference and specificity. GINPs demonstrate broad inhibition activity against both tier 1 and tier 2 HIV-1 strains with a pM-level IC50 and exhibit a significant inhibitory effect on long-term viral replication by more than 95%. The strategy provides a promising method for the inhibition and therapy of HIV-1 infection.

Brain function abnormalities and neuroinflammation in people living with HIV-associated anxiety disorders.

Background: People living with HIV (PLWH) exhibits an increased susceptibility to anxiety disorders, concomitant with heightened vulnerability to aberrant immune activation and inflammatory responses, and endocrine dysfunction. There exists a dearth of scholarly investigations pertaining to the neurological, immune, and endocrine dimensions of HIV-associated anxiety disorders. Method: This study aimed to compare a group of 16 individuals diagnosed with HIV-associated anxiety disorders (HIV ANXs) according to the Diagnostic and statistical manual of mental disorders (5th ed.), with a HIV individual control group (HIV control) of 49 PLWH without mental disorders. Muti-modal magnetic resonance was employed to assess the brain function and structure of both groups. Seed-based functional connectivity (FC) was used to assess the regional intrinsic brain activity and the influence of regional disturbances on FC with other brain regions. Peripheral blood cytokines and chemokines concentrations were measured using liquid chip and ELISA. Results: Amplitude of low-frequency fluctuations in the right inferior temporal gyrus (ITG) was increased. There is a significant decreased regional homogeneity in HIV ANXs in the right superior occipital gyrus (SOG). The right ITG and the right SOG were separately set as the seed brain region of interest (ROI 1 and ROI 2) to be analyzed the FC. FC decreased in HIV ANXs between ROI1 and the right middle occipital gyrus, the right SOG, FC between ROI2 and left ITG increased in HIV ANXs. No significant structural difference was found between two groups. Pro-inflammatory chemokines showed higher levels in the HIV ANXs. Pro-inflammatory cytokines, neurotrophic factors, and endocrine factors were significantly correlated with alterations in brain function. Conclusion: This study suggests that patients with HIV-associated anxiety disorders may exhibit abnormalities in neurologic, immune, and endocrine functioning. Consequently, it is imperative to implement additional screening and intervention measures for anxiety disorders among PLWH.

How can we establish animal models of HIV-associated lymphoma?

Human immunodeficiency virus (HIV) infection is strongly associated with a heightened incidence of lymphomas. To mirror the natural course of human HIV infection, animal models have been developed. These models serve as valuable tools to investigate disease pathobiology, assess antiretroviral and immunomodulatory drugs, explore viral reservoirs, and develop eradication strategies. However, there are currently no validated in vivo models of HIV-associated lymphoma (HAL), hampering progress in this crucial domain, and scant attention has been given to developing animal models dedicated to studying HAL, despite their pivotal role in advancing knowledge. This review provides a comprehensive overview of the existing animal models of HAL, which may enhance our understanding of the underlying pathogenesis and approaches for malignancies linked to HIV infection.

CB-0821, a novel CC chemokine receptor 5 (CCR5) inhibitor with improved binding efficacy proposed as anti-HIV candidate: Computational and in vitro approach.

The CC chemokine receptor 5 (CCR5) serves a pivotal role in human immunodeficiency virus 1 (HIV-1) infection by acting as a co-receptor and facilitating the binding of the viral envelope glycoprotein (env). Maraviroc (MVC), a Food and Drug Administration-approved monocarboxylic acid amide, is one of the CCR5 inhibitors employed in HIV treatment. Despite the existence of approved drugs, the emergence of drug resistance underscores the necessity for novel compounds to combat resistance and enhance therapeutic efficacy. In this study, CB-0821, identified from the ChemBridge library, emerged as a promising CCR5 inhibitor. Molecular dynamics simulations indicate comparable dynamic properties for CB-0821 and MVC. In silico comparisons with other CCR5 inhibitors emphasize CB-0821's superior binding affinity, positioning it as a potential lead compound. Evaluations of the dissociation constant (Ki) and absorption, distribution, metabolism, and excretion predictions suggest CB-0821 as a well-tolerated drug. Furthermore, the dose-dependent inhibition of CCR5 by CB-0821 in Peripheral blood mononuclear cells (PBMCs) (ranging from 10 to 200 nM) demonstrates efficacy, coupled with nontoxicity to Vero cells at concentrations up to 500 nM. These results underscore the potential of CB-0821 in HIV antiviral therapy, calling for additional preclinical validations before advancing to clinical considerations.

The prevalence of pneumothorax in human immunodeficiency virus patients. A single center study.

OBJECTIVES: To assess the prevalence, risk factors, and associated complications of pneumothorax that are present in patients with human immunodeficiency virus (HIV) at our institution and to provide an updated local study addressing the association between pneumothorax and HIV. METHODS: This retrospective cohort study examined 161 patients who were admitted with a diagnosis of HIV from June 2017 to May 2022. They were divided into 2 groups depending on the presence of pneumothorax during their stay. Multiple variables were studied, including age, gender, tuberculosis infection, pneumocystis jiroveci pneumonia (PJP)infection, bacterial pneumonia, and pneumothorax type and treatment course. RESULTS: There were 11 patients diagnosed with pneumothorax (prevalence rate: 6.8%). Bacterial lung infection was found in 9 (81.8%) of these patients, while fungal infection was found in 6 (54.5%) (p<0.001, 0.010). The MTB was found in 3 (27.3%) patients (p=0.728), while none were infected with PJP. Intercostal tube insertion was attempted in 9 (81.8%) patients, the mean duration of tube stay was 39.3±30.7 days, and the mortality rate was 72.7% (p=0.007). CONCLUSION: Pneumothorax in patients with HIV is a manifestation of the progression of the disease and its poor outcome. It has a complicated treatment course and a high mortality rate.

Role of I182, R187, and K188 Amino Acid Residues in the Catalytic Domain of HIV-1 Integrase in the Processes of Reverse Transcription and Integration.

Structural organization of HIV-1 integrase is based on a tetramer formed by two protein dimers. Within this tetramer, the catalytic domain of one subunit of the first dimer interacts with the N-terminal domain of the second dimer subunit. It is the tetrameric structure that allows both ends of the viral DNA to be correctly positioned relative to the cellular DNA and to realize catalytic functions of integrase, namely 3'-processing and strand transfer. However, during the HIV-1 replicative cycle, integrase is responsible not only for the integration stage, it is also involved in reverse transcription and is necessary at the stage of capsid formation of the newly formed virions. It has been suggested that HIV-1 integrase is a structurally dynamic protein and its biological functions depend on its structure. Accordingly, studying interactions between the domains of integrase that provide its tetrameric structure is important for understanding its multiple functions. In this work, we investigated the role of three amino acids of the catalytic domain, I182, R187, and K188, located in the contact region of two integrase dimers in the tetramer structure, in reverse transcription and integration. It has been shown that the R187 residue is extremely important for formation of the correct integrase structure, which is necessary at all stages of its functional activity. The I182 residue is necessary for successful integration and is not important for reverse transcription, while the K188 residue, on the contrary, is involved in formation of the integrase structure, which is important for the effective reverse transcription.