Progression Of Human Immunodeficiency Virus Infection Research Articles

Distribution of the Prevalence of Human Leukocyte Antigen (HLA)-B*57:01 Positivity in HIV-1 Infected Individuals and Its Effects on Treatment: Türkiye Map-Buhasder Working Group

Human immunodeficiency virus (HIV)/acquired immundeficiency syndrome (AIDS) is a critical global public health problem that significantly affects both life expectancy and the overall quality of life of individuals in all age groups. The landscape of HIV infection has changed significantly in recent years due to the introduction of effective combination antiretroviral therapies (ART). A key component of first-line ART regimens for HIV treatment is abacavir, a nucleoside HIV reverse transcriptase inhibitor. Although abacavir is effective in suppressing viral replication and managing disease, its clinical utility is overshadowed by the potential for life-threatening hypersensitivity reactions in HLA-B*57:01-positive patients. In our country, local data obtained from various centers regarding the prevalence of HLA-B*57:01 in HIV-1-infected patients are available. In this study, it was aimed to determine the prevalence of the HLA-B*57:01 genotype in HIV-infected patients who were followed up and treated in many regions of our country. This retrospective study consists of the data of the patients aged 18 years and over diagnosed with HIV-1 infection between 01.01.2019 and 31.07.2022. Age, gender, place of birth, mode of transmission of the disease, death status, CD4+ T cell count and HIV RNA levels at the first clinical presentation, HLA-B*57:01 positivity, and the method used, clinical stage of the disease, virological response time with the treatment they received were recorded from the patient files. Data were collected from 16 centers and each center used different methods to detect HLA-B*57:01. These methods were sequence-specific oligonucleotide probe hybridization (SSOP), DNA sequence-based typing (SBT), single-specific primer-polymerase chain reaction (SSP-PCR), allele-specific PCR (AS-PCR) and quantitative PCR (Q-PCR). A total of 608 HIV-infected individuals, 523 males (86%) and 85 females (14%), were included in the study. The mean age of the patients was 36.9 ± 11.9 (18-73) years. The prevalence of HLA-B*57:01 allele was found to be 3.6% (22 patients). The number of CD4+ T lymphocytes in HLA-B*57:01 allele-positive patients was > 500/ mm3 in 10 patients (45.5%), while the number of CD4+ T lymphocytes in HLA-B*57:01 negative patients was > 500/mm3 in 216 patients (36.9%) (p> 0.05). Viral load at the time of diagnosis was found to be lower in patients with positive HLA-B*57:01 allele but it was not statistically significant (p> 0.05). Although different treatment algorithms were used in the centers following the patients, it was observed that the duration of virological response was shorter in HLA-B*57:01 positive patients (p= 0.006). Although the presence of the HLA-B*57:01 allele has a negative impact due to its association with hypersensitivity, it is likely to continue to attract interest due to its association with slower progression of HIV infection and reduced risk of developing AIDS. In addition, although the answer to the question of whether it is cost-effective to screen patients for HLA-B*57:01 before starting an abacavir-containing ART regimen for the treatment of HIV infection is being sought, it seems that HIV treatment guidelines will continue to recommend screening to identify patients at risk in this regard.

Anemia as a Prognostic Marker for Disease Progression in HIV Infection

Anemia, a prevalent hematologic manifestation in individuals living with Human Immunodeficiency Virus (HIV) infection, has garnered considerable attention as a prognostic indicator for disease progression and adverse clinical outcomes. This abstract presents a comprehensive review elucidating the intricate relationship between anemia and the progression of HIV infection, incorporating epidemiological trends, underlying pathophysiological mechanisms, clinical implications, and prognostic significance. Despite advances in antiretroviral therapy (ART), anemia remains a frequent complication in HIVinfected individuals, posing substantial challenges to patient management. This paper aims to provide a nuanced understanding of anemia's role as a prognostic marker, surpassing its conventional characterization as a hematologic abnormality in the context of HIV infection. Anemia's role as a predictive marker for adverse clinical outcomes in HIV patients is explored, encompassing increased mortality rates, heightened risk of opportunistic infections, accelerated disease progression, and compromised quality of life. The review delves into its prognostic significance, shaping therapeutic decisions and prognostic assessments. This paper encapsulates the criticality of anemia as a prognostic marker for disease progression in HIV infection. Understanding its epidemiology, pathophysiological mechanisms, clinical implications, and prognostic significance is pivotal for informed clinical decision-making, prognostic assessments, and optimizing care paradigms in HIV management. Keywords: Anemia, Prognostic Marker, Disease Progression and HIV

Viral load: We need a new look at an old problem?

The concept of viral load was introduced in the 1980s to measure the amount of viral genetic material in a person's blood, primarily for human immunodeficiency virus (HIV). It has since become crucial for monitoring HIV infection progression and assessing the efficacy of antiretroviral therapy. However, during the coronavirus disease 2019 pandemic, the term "viral load" became widely popularized, not only for the scientific community but for the general population. Viral load plays a critical role in both clinical patient management and research, providing valuable insights for antiviral treatment strategies, vaccination efforts, and epidemiological control measures. As measuring viral load is so important, why don't researchers discuss the best way to do it? Is it simply acceptable to use raw Ct values? Relying solely on Ct values for viral load estimation can be problematic due to several reasons. First, Ct values can vary between different quantitative polymerase chain reaction assays, platforms, and laboratories, making it difficult to compare data across studies. Second, Ct values do not directly measure the quantity of viral particles in a sample and they can be influenced by various factors such as initial viral load, sample quality, and assay sensitivity. Moreover, variations in viral RNA extraction and reverse-transcription steps can further impact the accuracy of viral load estimation, emphasizing the need for careful interpretation of Ct values in viral load assessment. Interestingly, we did not observe scientific articles addressing different strategies to quantify viral load. The absence of standardized and validated methods impedes the implementation of viral load monitoring in clinical management. The variability in cell quantities within samples and the variation in viral particle numbers within infected cells further challenge accurate viral load measurement and interpretation. To advance the field and improve patient outcomes, there is an urgent need for the development and validation of tailored, standardized methods for precise viral load quantification.

Comparison of the Biological Basis for Non-HIV Transmission to HIV-Exposed Seronegative Individuals, Disease Non-Progression in HIV Long-Term Non-Progressors and Elite Controllers.

HIV-exposed seronegative individuals (HESIs) are a small fraction of persons who are multiply exposed to human immunodeficiency virus (HIV), but do not exhibit serological or clinical evidence of HIV infection. In other words, they are groups of people maintaining an uninfected status for a long time, even after being exposed to HIV several times. The long-term non-progressors (LTNPs), on the other hand, are a group of HIV-infected individuals (approx. 5%) who remain clinically and immunologically stable for an extended number of years without combination antiretroviral therapy (cART). Meanwhile, elite controllers are comprise a much lower number (0.5%) of HIV-infected persons who spontaneously and durably control viremia to below levels of detection for at least 12 months, even when using the most sensitive assays, such as polymerase chain reaction (PCR) in the absence of cART. Despite the fact that there is no universal agreement regarding the mechanisms by which these groups of individuals are able to control HIV infection and/or disease progression, there is a general consensus that the mechanisms of protection are multifaceted and include genetic, immunological as well as viral factors. In this review, we analyze and compare the biological factors responsible for the control of HIV in these unique groups of individuals.

Influence of HIV infection on clinical course of the new coronavirus infection (COVID-19)

BACKGROUND: Human immunodeficiency virus (HIV)-associated severe immunosuppression, high viral load, non-HIV-related comorbidities and conditions, and lack of antiretroviral therapy may exacerbate the clinical course of coronavirus disease 2019 (COVID-19).
 AIM: To assess the effect of HIV infection on the clinical course of COVID-19, disease severity, and its outcomes.
 MATERIALS AND METHODS: Medical records of 35,328 patients who had COVID-19 in 2020 were analyzed, including 46 cases of COVID-19 in individuals with HIV infection. Clinical variants and COVID-19 severity, frequency of COVID-19 detection by polymerase chain reaction, CD4 lymphocyte count, viral load in individuals with HIV infection, and mortality rates were assessed.
 RESULTS: In 76% of patients with coinfection, signs of HIV infection progression, opportunistic infections, and concomitant diseases were noted. Moreover, 52.2% of the patients analyzed were users of psychoactive substances. Among patients with HIV and COVID-19, men predominated in groups aged 30 years, whereas among the HIV-negative population, women were predominant in groups aged 18 years. The proportion of severe COVID-19 in individuals with HIV infection (47.8%) exceeds that in the group without HIV (12.3%). The mortality rate from COVID-19 in the HIV-infected group was more than seven times higher than that in the HIV-negative group (t=1.81; p=0.01).
 CONCLUSIONS: In the HIV-infected group, extremely severe COVID-19 was more common. Weakness, cough, shortness of breath, and myalgia were significantly more common in the HIV-infected group. Moreover, the HIV-infected group with an undetectable viral load and adequate CD4 lymphocyte count in the blood was exposed to the same risks of the disease and its progression as the HIV-negative group.

Mucocutaneous manifestations of HIV/AIDS infection: literature review

Mucocutaneous manifestations are the first recognized human immunodeficiency virus (HIV) infections. More than 90% of HIV-infected patients develop at least one or more types of typical or atypical skin lesions during the disease. Mucocutaneous manifestation can also indicate the progression of HIV infection and cluster of differentiation 4 (CD4) cell count as an indicator of the development of acquired immunodeficiency syndrome (AIDS). It is important to know mucocutaneous manifestations and their correlation with the patient’s immune status to provide appropriate treatment to improve the patient’s quality of life.

Case report: Safety and efficacy of adalimumab in treating difficult-to-treat rheumatoid arthritis in a human immunodeficiency virus-positive patient, one year follow-up

Rheumatoid arthritis (RA) is a joint-disabling inflammatory disease associated with the pathology of synovitis. Some patients with RA are difficult to treat, using disease-modifying anti-rheumatic drugs (DMARDs). Biology and targeted synthetic DMARDs (b/tsDMARDs) are options for patients with RA. Acquired immunodeficiency syndrome (AIDS) is an infectious disease caused by the human immunodeficiency virus (HIV). Adalimumab is an anti-tumor necrosis factor therapy commonly used in patients with RA. However, there are no reports or related data on patients with RA-HIV/AIDS treated with adalimumab are available. In this report, we described the first successful case of a 60-year-old HIV-positive woman with difficult-to-treat RA treated with ADA after being screened for hepatitis virus, latent tuberculosis (LTBI), and other infections. She contracted HIV from sexual exposure while on adalimumab therapy. As the patient was resistant to first-line DMARDs, she continued adalimumab along with the initiation of highly active antiretroviral therapy (HAART). The patient was treated with adalimumab therapy for a year; her CD4+ lymphocyte count was normal, HIV-1 RNA decreased, and no new infections were triggered. The patient achieved clinical remission of RA. In conclusion, adalimumab is a safe option for patients with RA-HIV and may slow the progression of HIV infection. Furthermore, HAART has the potential to reduce joint pain and fatigue in patients with difficult-to-treat RA.ConclusionsAdalimumab is a safe option for patients with RA-HIV, and may slow down the progression of HIV infection. The HAART therapy has the potential to reduce joint pain and fatigue in patients with difficult-to-treat RA.

HIV Infection Progression Monitoring System Based on CD4 Counts and Wishart Distribution.

The human immunodeficiency virus (HIV) is a viral infection that destroys the human immune system, resulting in the acquired immunodeficiency syndrome (AIDS). The management and care of patients on antiretroviral therapy (ART) consumes a large portion of the health budget of many countries. ART improves the lives of the HIV patients. However, benefiting from the treatment remains to be low due to the nonadherence, adverse events, and treatment failure associated with the transmitted drug resistance mutations (TDRMs). Extra care is therefore required in prescribing switch of ART regimens for HIV-naive patients. We propose a disease monitoring system, which depends on how the HIV-naive patients respond to the ART regimen. We model cluster of differentiation 4 (CD4) counts data measured at every 3 months in a period of 48 weeks on a cohort of 87 HIV-naive patients on ART, from Zambia. We demonstrate how to apply the Bayesian Wishart distribution to model CD4 counts, leading to an informative HIV progression monitoring system. We found a steady increase in the average of the CD4 counts (from 219 to 315) for HIV-naive patients on the ART regimen. The average was still below the expected 500 CD4 counts for a normal person. The derived precision matrix shows an increase in probability of potency of the ART regimen, which ranges from 0.1261 to 0.8678. An early detection is crucial as it allows for timely switch of regimen from first to second line or to the third line. The proposed HIV disease progression monitoring system for HIV-naive patients on ART regimen that is based on CD4 counts could enable physicians make informed decisions on the management and care of the patients.

KIR2DL5B and HLA DRB1*12 alleles seems to be associated with protection against HIV-1 in serodiscordant couples in Burkina Faso.

The human immunodeficiency virus (HIV) belongs to the Retroviridae family and remains a public health problem in sub-Saharan Africa. Recent reports from WHO have shown that 33 million people died from HIV infections. HIV is one of the most serious fatal human diseases of the 20thand 21stcenturies. However, variations in genetic and immunological factors are associated with protection against HIV infection in uninfected people exposed to HIV. This is the case with naturals killers which play an important role in the progression or regression of HIV infection. The objective of this study is to characterize certain HLA (human leukocyte antigen) class II genes and KIR genes in HIV-1 serodiscordant couples in Burkina Faso. This study was carried out at Burkina Faso among nineteen (19) HIV-1 serodiscordant couples. Classical multiplex PCR (SSP-PCR) was used to characterize the presence or absence of the KIR genes and certain class II HLAs (DRB1*11 and DRB1*12). The characterization of the KIR and HLA genes DRB1*11, DRB1*12 in this study demonstrated that the inhibitor KIR2DL5B, would confer protection against HIV-1 infection in seronegative partners (odd ratio [OR] = 0.13 [0.02-0.72]and p = 0.029), and the HLA DRB1*12 allele was associated with protection against HIV-1 infection in seronegative partners (OR = 0.16 [0.03-0.77]and p = 0.038). AA and Bx haplotypes were not found to be associated with HIV-1 infection in serodiscordant couples. This study confirms the involvement of the KIR genes in viral pathologies such as HIV-1 infection. Future larger-scale studies may provide a better understanding of the molecular mechanism by which the KIR haplotype and combination of KIR/HLA are associated with protection against HIV infection.

The relationship of antibodies detected in the Western Blot test with clinical and immunological stages in HIV-infected patients

Background/Aim: The laboratory diagnosis of human immunodeficiency virus (HIV) infection is based on detection of anti-HIV antibodies in an initial ELISA (enzyme-linked immunosorbent assay) test and its confirmation with the Western Blot (WB) procedure. Even though the specificity of WB is high for the detection of antibodies against various viral proteins, there are important differences in the timing of the appearance of antibody bands and intensities in different stages of HIV infection. The aim of this study was to evaluate antibodies detected in WB testing and the relationship to clinical and immunological stages in HIV-infected patients. Methods: Newly diagnosed 78 patients with HIV/AIDS (Acquired Immunodeficiency Syndrome) in our outpatient department between April 2009 and September 2012 were included in the study as a retrospective cohort. Age, gender, complaints, clinical signs, CD4+ T lymphocyte counts and HIV RNA level at diagnosis were collected retrospectively from medical records. WB band patterns obtained from the reference laboratory of the Istanbul Public Health Center were examined retrospectively. Results: Of the 78 HIV/AIDS cases, 68 (87.2%) were male. Mean age was 38.87(13.09) years (range, 17-83 years). Median CD4+ T lymphocyte count at diagnosis was 410.2 /mm³ (range, 3-1114). Mean HIV RNA level at diagnosis was 592.894 copies/ml. Rare band profiles were seen in 29.4% (23/78). According to World Health Organization (WHO) clinical staging, 59 (75.6%) patients were at stage I, 4 at stage II, 10 at stage III and 5 at stage IV. Gp120, gp160 and gp41, known as envelope glycoproteins in WB band antibodies, were seen in all patients. There was determined to be a decrease in the p17, p51, p55 and p39 bands in WB tests of the advanced grade (Grade IV) of HIV infection. Conclusions: Reduction of p17, p51, p55, p39 antibodies in advanced stages were related with the progression of HIV infection. This shows that WB test is an important parameter not only in the diagnosis of HIV infection, but also in the follow-up of clinical progression in the absence of these antibodies.

Occurrence of DAT1 (VNTR) Polymorphism in Individuals with HIV Infection

Background: Antiretroviral treatment (ART) has been reported to make changes in the functioning of dopaminergic neurons by altering the expression of dopamine active transporter (DAT). ART containing efavirenz drug has been related to show the adverse reactions on the central nervous system (CNS). Reported literature indicates the correlation of DAT19/10 genotype with the risk of progression of human immunodeficiency virus (HIV) infection. Objective: The aim of this study was to assess the polymorphism in the human gene DAT1, including variable number tandem repeats (VNTR) from individuals having an infection of HIV. Methods: Genotyping was completed by performing a polymerase chain reaction (PCR) in a total of 165 HIV-positive patients on ART treatment (34 were HIV-infected patients with hepatotoxicity, 131 HIV-infected patients) and 160 healthy controls without HIV infection. Results: Incidence of DAT19/9, 8/9 genotypes, and allele with 9 repeats were higher in individuals having hepatotoxicity compared to those who do not have hepatotoxicity (5.9 vs. 0.8%, OR = 7.73; 2.9 vs. 0.8%, OR = 3.86; 20.58% vs. 14.12%, OR = 1.56). DAT19/10 genotype was related to severity of hepatotoxicity (OR = 1.86; P = 0.05). Upon comparison of genotype between individuals who do not have hepatotoxicity but had HIV infection and healthy controls without HIV infection, the dispersion of DAT1 10/11, 6/10 genotypes were greater in individuals with HIV infection (1.5% vs. 0.6%, OR = 2.73; 3.1% vs. 1.3%, OR = 2.73). DAT19/10 genotype was related to the people of advanced stage of HIV infection (OR = 2.05, P = 0.04). A higher incidence of DAT19/10 genotype was found in individuals with early stage of HIV infection than healthy controls (26.3 vs. 15.6%, OR = 1.93). In alcohol and tobacco consuming individuals with HIV infection and hepatotoxicity, DAT19/10 genotype has demonstrated hazard in the progression of HIV infection and an increased severity of hepatotoxic condition (OR = 1.40, P = 0.91, OR = 1.50; P = 0.91 and OR = 1.57, P = 0.39; OR = 2.70; P = 0.53). In patients with hepatotoxicity, nevirapine utilization with DAT19/10 genotype demonstrated an increase in severity of hepatotoxicity (OR = 4.00, P = 0.41). In individuals with HIV infection and hepatotoxicity, alcohol and nevirapine usage, along with DAT1 9/10 genotype, indicated a risk for progression of HIV infection and severity of hepatotoxicity (OR = 1.47, P = 0.85; OR = 1.73; P = 0.32). Conclusion: The genetic polymorphism with DAT19/10 genotype was linked with the progression of HIV infection and in the advancement of HIV-related illnesses.

ВИЧ-инфекция у пациентов пожилого возраста: клинические случаи

В статье представлены клинические случаи ВИЧ-инфекции, диагностированной у пациентов пожилого возраста: мужчины в возрасте 70 лет и женщины 68 лет, длительно совместно проживавших. Несмотря на приблизительно одинаковый возраст пациентов на момент постановки диагноза, у женщины имели место более «продвинутая», 3-я клиническая стадия ВИЧ-инфекции, более выраженный иммунодефицит (СD4+ Т-лимфоциты — 285 кл/мкл) по сравнению с мужчиной, у которого при выявлении заболевания установлена 1-я клиническая стадия ВИЧ-инфекции, умеренный иммунодефицит (СD4+ Т-лимфоциты — 375 кл/мкл). Однако на фоне проводимой антиретровирусной терапии (АРТ) у пациентки зафиксирован рост показателя CD4+ Т-лимфоцитов. В настоящее время состояние пациентки стабильно удовлетворительное, продолжительность жизни после установления ВИЧ-инфекции на сегодня составила 7 лет. У пациента заболевание протекало более агрессивно, так как он отказывался от проведения АРТ, что привело к быстрому прогрессированию ВИЧ-инфекции, развитию СПИД-ассоциированной опухоли — саркомы Капоши, приведшей к летальному исходу. Продолжительность его жизни после установления диагноза ВИЧ-инфекции составила 4 года.

Salivary biomarkers associated with the progression of disease in people living with HIV: A scoping review protocol.

Background: Biomarkers are measurable indicators of normal biological processes, which provide an objective assessment of the physiologic state of living systems. Saliva contains several biomarkers that serve as a diagnostic tool in health and disease. Evaluation of a multitude of salivary components could potentially predict the clinical outcome. This is especially critical in a chronic, potentially life-threatening condition like human immunodeficiency virus (HIV) infection. Scrupulous evaluation of relevant biomarkers could facilitate the early detection of HIV, determine the stage of infection and monitor the disease progression. Currently, there is a paucity of validated biomarkers in saliva predicting the disease progression in people living with HIV. In this scoping review, we aim to provide an overview of the available evidence on salivary markers associated with the progression of disease in people living with HIV. Methods: The authors shall develop a tailored search strategy for each database using relevant keywords. We will search for eligible studies indexed in the following databases: MEDLINE, EMBASE, and the Cochrane Library, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and gray literature. We will restrict the search to studies published in the English language. Following deduplication, all search results will be exported to the EPPI reviewer web, where two independent reviewers using a data extraction tool developed and pretested by the review authors will screen eligible studies. The result of this review will be reported using the Preferred Reporting Items for Systematic Review and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) checklist and reporting guidelines. Discussion: The proposed scoping review protocol will enable the identification and assessment of salivary biomarkers, which can predict disease progression in patients with HIV infection. The synthesis of evidence from this review will assist in improving our current understanding of biomarkers used to evaluate the progression of HIV infection.

Landscape of T Cells Transcriptional and Metabolic Modules During HIV Infection Based on Weighted Gene Co-expression Network Analysis.

Human immunodeficiency virus (HIV) causes acquired immunodeficiency syndrome (AIDS). HIV infection affects the functions and metabolism of T cells, which may determine the fate of patients; however, the specific pathways activated in different T-cell subtypes (CD4+ and CD8+ T cells) at different stages of infection remain unclear. We obtained transcriptome data of five individuals each with early HIV infection, chronic progressive HIV infection, and no HIV infection. Weighted gene co-expression network analysis was used to evaluate changes in gene expression to determine the antiviral response. An advanced metabolic algorithm was then applied to compare the alterations in metabolic pathways in the two T-cell subtypes at different infection stages. We identified 23 and 20 co-expressed gene modules in CD4+ T and CD8+ T cells, respectively. CD4+ T cells from individuals in the early HIV infection stage were enriched in genes involved in metabolic and infection-related pathways, whereas CD8+ T cells were enriched in genes involved in cell cycle and DNA replication. Three key modules were identified in the network common to the two cell types: NLRP1 modules, RIPK1 modules, and RIPK2 modules. The specific role of NLRP1 in the regulation of HIV infection in the human body remains to be determined. Metabolic functional analysis of the two cells showed that the significantly altered metabolic pathways after HIV infection were valine, leucine, and isoleucine degradation; beta-alanine metabolism; and PPAR signaling pathways. In summary, we found the core gene expression modules and different pathways activated in CD4+ and CD8+ T cells, along with changes in their metabolic pathways during HIV infection progression. These findings can provide an overall resource for establishing biomarkers to facilitate early diagnosis and potential guidance for new targeted therapeutic strategies.

Psychosocial Stress Alters the Immune Response and Results in Higher Viral Load During Acute Simian Immunodeficiency Virus Infection in a Pigtailed Macaque Model of Human Immunodeficiency Virus.

Although social distancing is a key public health response during viral pandemics, psychosocial stressors, such as social isolation, have been implicated in adverse health outcomes in general [1] and in the context of infectious disease, such as human immunodeficiency virus (HIV) [2, 3]. A comprehensive understanding of the direct pathophysiologic effects of psychosocial stress on viral pathogenesis is needed to provide strategic and comprehensive care to patients with viral infection. To determine the effect of psychosocial stress on HIV pathogenesis during acute viral infection without sociobehavioral confounders inherent in human cohorts, we compared commonly measured parameters of HIV progression between singly (n = 35) and socially (n = 41) housed simian immunodeficiency virus (SIV)-infected pigtailed macaques (Macaca nemestrina). Singly housed macaques had a higher viral load in the plasma and cerebrospinal fluid and demonstrated greater CD4 T-cell declines and more CD4 and CD8 T-cell activation compared with socially housed macaques throughout acute SIV infection. These data demonstrate that psychosocial stress directly impacts the pathogenesis of acute SIV infection and imply that it may act as an integral variable in the progression of HIV infection and potentially of other viral infections.

Unmapped exome reads implicate a role for Anelloviridae in childhood HIV-1 long-term non-progression

Human immunodeficiency virus (HIV) infection remains a significant public health burden globally. The role of viral co-infection in the rate of progression of HIV infection has been suggested but not empirically tested, particularly among children. We extracted and classified 42 viral species from whole-exome sequencing (WES) data of 813 HIV-infected children in Botswana and Uganda categorised as either long-term non-progressors (LTNPs) or rapid progressors (RPs). The Ugandan participants had a higher viral community diversity index compared to Batswana (p = 4.6 × 10−13), and viral sequences were more frequently detected among LTNPs than RPs (24% vs 16%; p = 0.008; OR, 1.9; 95% CI, 1.6–2.3), with Anelloviridae showing strong association with LTNP status (p = 3 × 10−4; q = 0.004, OR, 3.99; 95% CI, 1.74–10.25). This trend was still evident when stratified by country, sex, and sequencing platform, and after a logistic regression analysis adjusting for age, sex, country, and the sequencing platform (p = 0.02; q = 0.03; OR, 7.3; 95% CI, 1.6–40.5). Torque teno virus (TTV), which made up 95% of the Anelloviridae reads, has been associated with reduced immune activation. We identify an association between viral co-infection and prolonged AIDs-free survival status that may have utility as a biomarker of LTNP and could provide mechanistic insights to HIV progression in children, demonstrating the added value of interrogating off-target WES reads in cohort studies.

Salivary biomarkers associated with the progression of disease in people living with HIV: A scoping review

Background: Biomarkers are measurable indicators of normal biological processes, which provide an objective assessment of the physiologic state of living systems. Saliva contains several biomarkers that serve as a diagnostic tool in health and disease. Evaluation of a multitude of salivary components could potentially predict the clinical outcome. This is especially critical in a chronic, potentially life-threatening condition like human immunodeficiency virus (HIV) infection. Scrupulous evaluation of relevant biomarkers could facilitate the early detection of HIV, determine the stage of infection and monitor the disease progression. Currently, there is a paucity of validated biomarkers in saliva predicting the disease progression in people living with HIV. In this scoping review, we aim to provide an overview of the available evidence on salivary markers associated with the progression of disease in people living with HIV. Methods: The authors shall develop a tailored search strategy for each database using relevant keywords. We will search for eligible studies indexed in the following databases: MEDLINE, EMBASE, and the Cochrane Library, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and gray literature. We will restrict the search to studies published in the English language. Following deduplication, all search results will be exported to the EPPI reviewer web, where two independent reviewers using a data extraction tool developed and pretested by the review authors will screen eligible studies. The result of this review will be reported using the Preferred Reporting Items for Systematic Review and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) checklist and reporting guidelines. Discussion: The proposed scoping review protocol will enable the identification and assessment of salivary biomarkers, which can predict disease progression in patients with HIV infection. The synthesis of evidence from this review will assist in improving our current understanding of biomarkers used to evaluate the progression of HIV infection.

Hematologic alterations and early mortality in a cohort of HIV positive African patients.

IntroductionInfection with Human Immunodeficiency Virus (HIV) is highly prevalent worldwide, especially in Sub-Saharan Africa, where anaemia is also widespread. HIV infection is known to be associated with anaemia and various other haematologic alterations, but little data on correlation with immunological and virologic conditions in treatment-naïve patients and impact on mortality are available. Our study aims to investigate hematologic features in HIV-infected individuals in Malawi and Mozambique and assesses possible correlations with early morality.Material and methodsWe conducted a retrospective analysis of baseline data (general details, nutritional status, full blood count and HIV infection progress data) and 12 months follow-up status for HIV+ adult patients in 22 health facilities in Malawi (11 sites) and Mozambique (11 sites) run by DREAM program. Anagraphic details, anthropometric characteristics, full blood count, CD4+ count and Viral Load data were collected from electronical medical records (EMR) for all the HIV-positive, treatment-naïve patients starting care in the sites in the period January 2007 –December 2016. Follow-up status after one year since enrolment in care was also considered. All the data extracted from the EMR were included in a dataset and then analysed. Univariate and multivariate analysis were conducted through logistical regression to investigate associations, and survival analysis analysed in a Cox regression model.ResultsOn the whole, 22.657 patients were included; severe and moderate anaemia were observed in 1.174 (8,2%) and 4.703 (21,9%) patients respectively. Gender, nutritional status, CD4+ count, and viral load (VL) were associated with anaemia, leukopenia, and thrombocytopenia. Among 21.166 fully evaluable patients, 8.494 (40,1%) had at least one cytopenia. Any cytopenia was present in 1/3 of patients with normal nutritional status and less advanced HIV infection, and it wouldn’t be diagnosed in a basic HIV care setting. During the first year of treatment, 1.725 subjects (7,6% of the entire sample) died. Anaemia, lower Red blood cells and platelets counts correlated with mortality in the first year of care, independently by body mass index, haemoglobin, CD4+ count and VL.ConclusionsNotwithstanding anaemia is known to be associated with HIV infection at diagnosis, full blood count is not routinely performed in many African countries. Our results emphasize that including the study of a broader set of parameters in the routine HIV care services in Sub-Saharan Africa would provide significant clinical information able to predict other alterations and poor outcomes.

The Genome-wide Methylation Profile of CD4+ T Cells From Individuals With Human Immunodeficiency Virus (HIV) Identifies Distinct Patterns Associated With Disease Progression.

BackgroundHuman genetic variation—mostly in the human leukocyte antigen (HLA) and C–C chemokine receptor type 5 (CCR5) regions—explains 25% of the variability in progression of human immunodeficiency virus (HIV) infection. However, it is also known that viral infections can modify cellular DNA methylation patterns. Therefore, changes in the methylation of cytosine-guanine (CpG) islands might modulate progression of HIV infection.MethodsIn total, 85 samples were analyzed: 21 elite controllers (EC), 21 subjects with HIV before combination antiretroviral therapy (cART) (viremic, 93 325 human immunodeficiency virus type 1 [HIV-1] RNA copies/mL) and under suppressive cART (cART, median of 17 months, <50 HIV-1 RNA copies/mL), and 22 HIV-negative donors (HIVneg). We analyzed the methylation pattern of 485 577 CpG in DNA from peripheral CD4+ T lymphocytes. We selected the most differentially methylated gene (TNF) and analyzed its specific methylation, messenger RNA (mRNA) expression, and plasma protein levels in 5 individuals before and after initiation of cART.ResultsWe observed 129 methylated CpG sites (associated with 43 gene promoters) for which statistically significant differences were recorded in viremic versus HIVneg, 162 CpG sites (55 gene promoters) in viremic versus cART, 441 CpG sites (163 gene promoters) in viremic versus EC, but none in EC versus HIVneg. The TNF promoter region was hypermethylated in viremic versus HIVneg, cART, and EC. Moreover, we observed greater plasma levels of TNF in viremic individuals than in EC, cART, and HIVneg.ConclusionsOur study shows that genome methylation patterns vary depending on HIV infection status and progression profile and that these variations might have an impact on controlling HIV infection in the absence of cART.

Toll-Like Receptor 2 Promoter -196 to -174 Deletion Affects CD4 Levels Along Human Immunodeficiency Virus Infection Progression.

Toll-like receptor 2 (TLR2) plays a key role in innate immune response recognizing molecular patterns expressed by pathogens. rs111200466 is a TLR2 promoter insertion/deletion polymorphism with contradictory data about its role in human immunodeficiency virus type 1 (HIV-1) infection. We analyzed rs111200466 in HIV-1 disease progression and showed a correlation with a faster progression to the CD4+ < 200 cells/μL outcome for deletion allele carriers (Cox regression analysis: hazard ratio, 2.4 [95% confidence interval, 1.4-4]; P = .001). When naive patients with CD4+ < 200 cells/μL started antiretroviral treatment, rs111200466-deletion carriers showed a trend toward a slower, recovery rate (time required to reach CD4+ > 350 cells/μL; Cox P = .36). Our data suggest rs111200466 as a prognosis factor for HIV-1 disease progression.