HIV-infected Individuals Research Articles

The hypoxia-regulated ectonucleotidase CD73 is a host determinant of HIV latency

Deciphering the mechanisms underlying viral persistence is critical to achieving a cure for human immunodeficiency virus (HIV) infection. Here, we implement a systems approach to discover molecular signatures of HIV latently infected CD4+ Tcells, identifying the immunosuppressive, adenosine-producing ectonucleotidase CD73 as a key surface marker of latent cells. Hypoxic conditioning, reflecting the lymphoid tissue microenvironment, increases the frequency of CD73+ CD4+ Tcells and promotes HIV latency. Transcriptomic profiles of CD73+ CD4+ Tcells favor viral quiescence, immune evasion, and cell survival. CD73+ CD4+ Tcells are capable of harboring a functional HIV reservoir and reinitiating productive infection exvivo. CD73 or adenosine receptor blockade facilitates latent HIV reactivation invitro, mechanistically linking adenosine signaling to viral quiescence. Finally, tissue imaging of lymph nodes from HIV-infected individuals on antiretroviral therapy reveals spatial association between CD73 expression and HIV persistence invivo. Our findings warrant development of HIV-cure strategies targeting the hypoxia-CD73-adenosine axis.

Skin microbiome profile in people living with HIV/AIDS in Cameroon.

The presence of pathogens and the state of diseases, particularly skin diseases, may alter the composition of human skin microbiome. HIV infection has been reported to impair gut microbiome that leads to severe consequences. However, with cutaneous manifestations, that can be life-threatening, due to the opportunistic pathogens, little is known whether HIV infection might influence the skin microbiome and affect the skin homeostasis. This study catalogued the profile of skin microbiome of healthy Cameroonians, at three different skin sites, and compared them to the HIV-infected individuals. Taking advantage on the use of molecular assay coupled with next-generation sequencing, this study revealed that alpha-diversity of the skin microbiome was higher and beta-diversity was altered significantly in the HIV-infected Cameroonians than in the healthy ones. The relative abundance of skin microbes such as Micrococcus and Kocuria species was higher and Cutibacterium species was significantly lower in HIV-infected people, indicating an early change in the human skin microbiome in response to the HIV infection. This phenotypical shift was not related to the number of CD4 T cell count thus the cause remains to be identified. Overall, these data may offer an important lead on the role of skin microbiome in the determination of cutaneous disease state and the discovery of safe pharmacological preparations to treat microbial-related skin disorders.

Coinfection of HCV among HIV-infected patients: Across-sectional study in rivers State, Nigeria

Background: Hepatitis C virus (HCV) has emerged as the cause of the second major epidemic of viral infection after human immunodeficiency virus (HIV) within the past two decades. HCV is the cause of more than three-quarters of liver-relate deaths in HIV-seropositive individuals and it is remarkable that today approximately one-quarter of HIV-infected individuals Aim: this study aimed at determining the prevalence of coinfection patterns of HCV among HIV infected individual in Rivers State, Nigeria. Materials and methods: A retrospective survey conducted on 350 HIV infected individual attending ART clinic at Rivers State University Teaching Hospital, Port Harcourt, Nigeria. Sociodemographic data were collected based on interviewer-based questionnaire, and clinical history was obtained from participants' medical records. Antibody analyses for HCV were done using ELISA method. Results: The prevalence of hepatitis C virus coinfection among HIV positive individual was 6(4.0%), The prevalence of HCV and HIV positive individual with regards to age was high within the age of 21 -40 5(2.4%). Prevalence based on gender was females 4(1.1%) and males 2(1.4%), prevalence of HIV/HCV co-infection with respect to marital status was high among the single 6(4.9%), prevalence of HIV/HCV co-infection with respect educational status was high with tertiary 3(3.5%) than the secondary 3(1.6%). The prevalence among the different occupational groups, business had the highest co-infection rate (1.1%) followed closely by Working class (0.8%). Higher HIV/HCV co-infection was observed among those with CD4 cell count 350-499 cells/μl (4.6%). Conclusion: However, the low burden of this hepatotropic virus coinfection calls for continued need to screen for HCV among individual infected with HIV before the start of ART.

Simian immunodeficiency virus-infected rhesus macaques with AIDS co-develop cardiovascular pathology and encephalitis.

Despite effective antiretroviral therapy, HIV co-morbidities remain where central nervous system (CNS) neurocognitive disorders and cardiovascular disease (CVD)-pathology that are linked with myeloid activation are most prevalent. Comorbidities such as neurocogntive dysfunction and cardiovascular disease (CVD) remain prevalent among people living with HIV. We sought to investigate if cardiac pathology (inflammation, fibrosis, cardiomyocyte damage) and CNS pathology (encephalitis) develop together during simian immunodeficiency virus (SIV) infection and if their co-development is linked with monocyte/macrophage activation. We used a cohort of SIV-infected rhesus macaques with rapid AIDS and demonstrated that SIV encephalitis (SIVE) and CVD pathology occur together more frequently than SIVE or CVD pathology alone. Their co-development correlated more strongly with activated myeloid cells, increased numbers of CD14+CD16+ monocytes, plasma CD163 and interleukin-18 (IL-18) than did SIVE or CVD pathology alone, or no pathology. Animals with both SIVE and CVD pathology had greater numbers of cardiac macrophages and increased collagen and monocyte/macrophage accumulation, which were better correlates of CVD-pathology than SIV-RNA. Animals with SIVE alone had higher levels of activated macrophage biomarkers and cardiac macrophage accumulation than SIVnoE animals. These observations were confirmed in HIV infected individuals with HIV encephalitis (HIVE) that had greater numbers of cardiac macrophages and fibrosis than HIV-infected controls without HIVE. These results underscore the notion that CNS and CVD pathologies frequently occur together in HIV and SIV infection, and demonstrate an unmet need for adjunctive therapies targeting macrophages.

Co-infection dynamics of COVID-19 and HIV/AIDS

Although there are many results that can be used to treat and prevent Coronavirus Disease 2019 (COVID-19) and Human Immunodeficiency Virus (HIV), these diseases continue to be public health concerns and cause socioeconomic consequences. Following compromised immunity, COVID-19 is considered to be a challenge for people with HIV. People with advanced HIV are considered a vulnerable population at high risk in several case studies that discuss COVID-19 and HIV co-infection. As there is no cure for HIV and there is a chance of contracting COVID-19 again, co-infection continues to pose a problem. The purpose of this study is to investigate the impact of intervention strategies and identify the role of different parameters in risking people living with HIV to death when they get infected with COVID-19. This is achieved through the development and rigorous analysis of a mathematical model that considers a population at risk of death due to COVID-19 and HIV. The model formulation provides a detailed explanation of the transmission dynamics of COVID-19 and HIV co-infection. The solution’s invariant region, positivity, and boundedness were established. The reproduction numbers of the sub-models and the co-infection model were determined. The existence and stability of equilibria, including backward bifurcation for the COVID-19 sub-model, were examined. The epidemiological significance of backward bifurcation is that the condition {mathscr {R}}_0 less than 1 for eliminating COVID-19, though necessary, is no longer sufficient. Parametric estimation and curve fitting were performed based on data from Ethiopia. Numerical simulations were employed to support and clarify the analytical findings and to show some parameter effects on COVID-19 and HIV co-infection. Accordingly, the simulations indicated that parameters gamma _c, gamma _h, epsilon, and kappa, related to HIV patients’ exposure to other diseases and the increase in infectiousness, have a positive role in increasing the number of co-infections. On the other hand, an increase in COVID-19 vaccination (xi) shows the suppression of co-infection cases. In addition, treating co-infected individuals for COVID-19, increasing treatment rates alpha and varphi, reduces the death risk of HIV-infected individuals due to the co-infection burden. It was implied that improving vaccine delivery programs and other medical interventions have important contributions to lowering the risk of COVID-19 infection-related fatalities in HIV patients.

Influence of HIV infection on cognition and overall intelligence in HIV-infected individuals: advances and perspectives.

It is now well understood that HIV-positive individuals, even those under effective ART, tend to develop a spectrum of cognitive, motor, and/or mood conditions which are contemporarily referred to as HIV-associated neurocognitive disorder (HAND), and which is directly related to HIV-1 infection and HIV-1 replication in the central nervous system (CNS). As HAND is known to induce difficulties associated with attention, concentration, and memory, it is thus legitimate and pertinent to speculate upon the possibility that HIV infection may well influence human cognition and intelligence. We therefore propose herein to review the concept of intelligence, the concept of cells of intelligence, the influence of HIV on these particular cells, and the evidence pointing to differences in observed intelligence quotient (IQ) scores between HIV-positive and HIV-negative individuals. Additionally, cumulative research evidence continues to draw attention to the influence of the gut on human intelligence. Up to now, although it is known that HIV infection profoundly alters both the composition and diversity of the gut microbiota and the structural integrity of the gut, the influence of the gut on intelligence in the context of HIV infection remains poorly described. As such, we also provide herein a review of the different ways in which HIV may influence human intelligence via the gut-brain axis. Finally, we provide a discourse on perspectives related to HIV and human intelligence which may assist in generating more robust evidence with respect to this issue in future studies. Our aim is to provide insightful knowledge for the identification of novel areas of investigation, in order to reveal and explain some of the enigmas related to HIV infection.

CD57 T cells associated with immunosenescence in adults living with HIV or AIDS.

Despite the advancement of human immunodeficiency virus (HIV)-related discoveries, new HIV infections still persist. With the advent of antiretroviral therapy, prognosis has migrated from acute to chronic HIV infection and inflammation, with the possibility of increased immune aging. We aimed to assess such immunosenescence by analysing CD27 and CD57 expression on the surface of T cells. This cross-sectional study was conducted between 2017 and 2018 on people living with HIV/AIDS (PLWHA) who attended an outpatient clinic of the Infectious Diseases Service of a university hospital and a geriatric reference service in Brazil. A standardized interview was conducted, and venous peripheral blood was collected for flow cytometry analysis. To assess immunosenescence, we compared CD27 and CD57 expression on the surface of T cells between adult and elderly individuals without HIV and adult PLWHA. All results for cells in terminal senescent stages in adult PLWHA more closely resembled those of elderly than adult participants without HIV (p > 0.05). The presence of CD27+ cells did not differ statistically among the three study groups when comparing immunological responders (IR) and immunological non-responders (INR); for the entire CD4+ T-cell population (including CD4 + CD8+ and CD4 + CD8- cells), the median count (25-75th) was higher in the INR (79.6%) than the IR (68.0%) group. HIV-infected individuals possessed a higher number of T lymphocytes with a molecular phenotype associated with immunosenescence, a lower proportion of T cells in the early stages of senescence (median 25-75th: 27.0%), and a higher proportion of T cells in the intermediate and final stages of senescence (median 25-75th: 16.1%) than adults without HIV (median 25-75th: 42.0% and 18.4%, respectively). Considering the higher number of senescent T lymphocytes, we observed in our PLWHA population-especially in the INR group (CD8CD57+ cells: 39.3% INR vs. 23.4% IR; CD4CD57+ cells: 44.0% INR vs. 27.7% IR)-may indicate a similar mortality risk phenotype from immune-preventable diseases.

Supragingival mycobiome of HIV-exposed-but-uninfected children reflects a stronger correlation with caries-free-associated taxa compared to HIV-infected or uninfected children.

Highly active antiretroviral treatment (HAART) has greatly reduced opportunistic infections in HIV-infected individuals. However, even with the use of HAART, HIV-infected individuals are still at an increased risk of oral diseases, including dental caries. Dental caries development is associated with microbial community shifts leading to community dysbiosis. HIV infection can significantly alter the bacteriome and mycobiome composition in the oral cavity; however, these impacts have not been assessed for caries initiation and progression. The aim of this study was to characterize the mycobiome for supragingival plaque samples from HIV-infected (HI), HIV-exposed-but-uninfected (HEU), and HIV-unexposed-and-uninfected (HUU) children with and without caries. To accomplish this, ITS1 amplicons of 127 samples were sequenced. We found that HIV infection and exposure resulted in changes to the supragingival plaque mycobiome for both health and caries. Overall, a reduction in community diversity as caries progressed was observed, with HI children having the lowest diversity and HEU children the highest. Candida albicans was the most abundant species identified, with 177 different amplicon sequence variants (ASVs). Two C. albicans ASVs dominated the data (53.0% and 38.5% of all taxonomic assignments). The more frequent ASV dominated HI and HUU communities, whereas the second dominated HEU communities. HEU children also had the lowest abundance of C. albicans and the highest number of health-associated taxa (taxa statistically associated with caries-free teeth).IMPORTANCEGlobally, caries is among the most frequent chronic childhood disease, and the fungal component of the microbial community responsible is poorly studied despite evidence that fungi contribute to increased acid production exacerbating enamel demineralization. HIV infection is another global health crisis. Perinatal HIV exposure with infection are caries risk factors; however, the caries experience in the context of perinatal HIV exposure without infection is less clear. Using high-throughput amplicon sequencing, we find taxonomic differences that become pronounced during late-stage caries. Notably, we show a stronger correlation with health-associated taxa for HIV-exposed-but-uninfected children when compared to unexposed and uninfected children. This aligns with a lower incidence of caries in primary teeth at age 6 or less for exposed yet uninfected children. Ultimately, these findings could contribute to improved risk assessment, intervention, and prevention strategies such as biofilm disruption and the informed design of pro-, pre-, and synbiotic oral therapies.

Ocular manifestations of HIV infection at Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa.

The pattern of HIV-associated eye disease has changed with ongoing advancements in highly active antiretroviral therapy (HAART). HIV-infected individuals now live longer, enabling us to observe the long-term effects of HIV and HAART on the eye. There are few recent studies on HIV-related ocular disease in sub-Saharan Africa. To describe the ocular manifestations of HIV in patients attending the Nthabiseng HIV clinic at Chris Hani Baragwanath Academic Hospital, Johannesburg, South Africa. A cross-sectional study was conducted in 2021 and 2022 using convenience sampling of patients at the HIV clinic. The participants' clinical history was taken, their files were reviewed, and they underwent ocular examination. Correlation between eyes was managed by taking disease in one eye as the presence of disease in the participant. Descriptive statistics were used to summarise participant characteristics. Univariate and multivariate logistic regression models were used to assess the odds ratio (OR) of developing HIV-associated ocular diseases, and a p-value of <0.05 was used to define statistical significance. There were 182 participants (139 females and 43 males), with a mean (standard deviation) age of 48.9 (10.6) years. The most common anterior segment diagnoses were conjunctival microangiopathy (34.6%), pinguecula (31.3%) and cataracts (30.2%), while the most common posterior segment finding was peripheral retinal scarring with features in keeping of previous cytomegalovirus retinitis (24.2%). Notably, only 1.1% of patients had HIV retinopathy. A CD4 count <200 cells/μL showed an increased OR for cataracts (OR 4.24; p=0.003) and any anterior segment diagnoses (OR 10.05; p=0.029), while a CD4 count ≥200 cells/μL showed an increased risk of conjunctival microangiopathy (OR 2.14; p=0.017). With the advent of HAART, ocular manifestations of HIV are changing and the incidence of severe ocular opportunistic infections and HIV retinopathy has decreased precipitously. Although this study has shown that patients with a CD4 count <200 cells/μL are at increased risk of developing anterior ocular manifestations of HIV, including cataracts, these diseases are relatively innocuous or easily treatable. Routine ocular screening of HIV patients seems to be substantially less important now than it was in the pre-HAART era.

Integrated analysis of gut and oral microbiome in men who have sex with men with HIV Infection.

Human immunodeficiency virus (HIV) infection leads to severe deficiency in host immunity by depletion of CD4+ T-cells, resulting in an imbalance between the human microbiome and host immune response. Alterations in both gut and oral microbiomes have been observed in people living with HIV (PLWH). However, the impact of an altered gut and oral microbiome on HIV disease progression and the relationship between them in PLWH have not been explored. In this longitudinal study, we enrolled acute HIV-infected men who have sex with men (MSM) (n = 15), chronic HIV-infected MSM (n = 15), and HIV-uninfected MSM controls (n = 15). We collected anal and throat swab samples at recruitment (W0) from all participants and at 12 wk after antiretroviral therapy (ART) (W12) from the patients and performed 16S rRNA gene sequencing of genomic DNAs extracted from these swabs. In HIV-infected individuals with CD4 T-cell counts < 350 cells/µL, the increase in abundance of Streptococcus in the oral microbiome was inversely correlated with that of Streptococcus in the gut microbiome (r = -0.490, P = 0.039). In addition, the lower CD4+ T-cell counts (<200 cells/µL) were associated with the higher abundance of Escherichia-Shigella and the lower abundance of Methylobacterium-Methylorubrum of the gut microbiome in HIV-infected individuals. We demonstrate the alteration of gut microbiome resulting from HIV infection and ART and the relationship between the gut and oral microbiome in PLWH and controls. These findings highlight the need for a better understanding of the interactions between the oral and gut microbiome and its potential role in HIV disease progression. IMPORTANCE Our longitudinal integrated study has shown the marked alterations in the gut and oral microbiome resulting from acute and chronic HIV infection and from antiretroviral therapy. Importantly, the relationship between oral and gut microbiomes in people living with acute and chronic HIV infection and "healthy" controls has also been explored. These findings might contribute to a better understanding of the interactions between the oral and gut microbiomes and its potential role in HIV disease progression.

Inclusion of nutritional counseling and mental health services in HIV/AIDS management: A paradigm shift.

Human immunodeficiency virus (HIV) infection is a public health challenge that can degenerate into acquired immunodeficiency syndrome (AIDS) if not properly managed. HIV infection shortens life expectancy to about 5 to 10 years compared to noninfected individuals. People living with HIV/AIDS (PLWHA) are prone to several health challenges as a result of a deranged immune system culminating in high morbidity and mortality. Depression is a common feature of PLWHA. Depression heightens the emergence of opportunistic infections in HIV-infected individuals, accelerates the progression to AIDS, and increased suicidal tendencies, morbidity, and mortality. Food insecurity with its resultant undernutrition contributes to HIV/AIDS-related deaths. Undernourished PLWHA are more prone to opportunistic infections due to poor immunity. Interestingly, proper diet intake can boost immunity, slow the progression of AIDS and opportunistic infections, enhance body weight, and retard depression tendencies. Undernutrition can also be ameliorated by incorporating nutritional counseling and oral nutrient supplementation in routine HIV/AIDS checkups. Therefore, to increase HIV/AIDS management outcomes, the integration of nutrition counseling, dietary supplements, and mental health services should be embraced. Thus, HIV/AIDS care centers should amplify these services. In this article, we isolated relevant studies from various databases, illuminated the interwoven relationship between HIV/AIDS, depression, and undernutrition, and also reemphasized the need for adequate nutritional intervention in the battle against HIV/AIDS. Thus, this study provides a reawakening call to focus on incorporating nutritional guides and mental health care in HIV/AIDS management protocols.

A Tale of Two Viruses: Seroepidemiological and a Cross-Sectional Insights into HIV/HBV Coinfection in Selected Hospitals in Rivers State, Nigeria

Background: Hepatitis B virus (HBV), a circular DNA virus with humans serving as the only reservoir, remains a worldwide public health problem. The similarity in transmission routes for HBV and HIV makes co-infection very common. Thus, this study aimed at unveiling the seroepidemiological patterns of HBV coinfections among HIV-infected individuals in some selected hospitals in Rivers State, Nigeria. Materials and methods: A cross-sectional study was conducted on 350 HIV-infected individuals attending ART clinics at selected hospitals in Rivers State, Nigeria. Sociodemographic data were collected based on interviewer-based questionnaire, and clinical history was obtained from participants' medical records. Serological analysis for HBsAg was done using ELISA method. Results: Of the 350 HIV-infected patients, 9(2.6%) were positive for HBsAg. The majority of HIV/HBV coinfected participants were in age groups &gt;41 (3.7%), females (2.9%), singles (3.0%), tertiary education holders (3.5%), and business owners (1.1%) as shown in Table 1. Furthermore, immunological and virological markers analysis revealed that HBV seropositivity is more common with patients having CD4 count of 350-499 cells/mm3 (6.2%) and viral loads as target not detected (TND) with 5.4%. Conclusion: This study observed an HIV/HBV coinfection rate of 2.6% which has further confirmed the persistence of HIV/HBV co-infection in Rivers State, Nigeria. Ongoing and persistent public health interventions among the study population are thereby advocated.

Characteristics and risk factors for readmission in HIV-infected patients with Talaromyces marneffei infection.

Talaromyces marneffei (T. marneffei) is an opportunistic fungal infection (talaromycosis), which is common in subtropical regions and is a leading cause of death in HIV-1-infected patients. This study aimed to determine the characteristics and risk factors associated with hospital readmissions in HIV patients with T. marneffei infection in order to reduce readmissions. We conducted a retrospective study of admitted HIV-infected individuals at the Fourth People's Hospital of Nanning, Guangxi, China, from 2012 to 2019. Kaplan-Meier analyses and Principal component analysis (PCA) were used to evaluate the effects of T. marneffei infection on patient readmissions. Additionally, univariate and multifactorial analyses, as well as Propensity score matching (PSM) were used to analyze the factors associated with patient readmissions. HIV/AIDS patients with T. marneffei-infected had shorter intervals between admissions and longer lengths of stay than non-T. marneffei-infected patients, despite lower readmission rates. Compared with non-T. marneffei-infected patients, the mortality rate for talaromycosis patients was higher at the first admission. Among HIV/AIDS patients with opportunistic infections, the mortality rate was highest for T. marneffei at 16.2%, followed by cryptococcus at 12.5%. However, the readmission rate was highest for cryptococcus infection (37.5%) and lowest for T. marneffei (10.8%). PSM and Logistic regression analysis identified leukopenia and elevated low-density lipoprotein (LDL) as key factors in T.marneffei-infected patients hospital readmissions. The first admission represents a critical window to intervene in the prognosis of patients with T. marneffei infection. Leukopenia and elevated LDL may be potential risk factors impacting readmissions. Our findings provide scientific evidence to improve the long-term outcomes of HIV patients with T. marneffei infection.

Survey on the cognition of the "undetectable equals untransmittable" concept among HIV-infected men who have sex with men receiving antiviral treatment

Objective: To explore the cognition of the "undetectable equals untransmittable" ("U=U") concept and associated factors among HIV-infected men who have sex with men (MSM) receiving antiviral treatment (ART) in Shenzhen, and provide evidence for designing promotion and advocacy strategies for the "U=U" concept. Methods: We recruited HIV-infected MSM receiving ART using convenient sampling method combined with routine follow-up in Shenzhen through conducting observational survey. The sample size was estimated to be 475. A questionnaire was administered to collect socio-demographic characteristics, sexual behaviors, ART, viral load testing and the cognition towards "U=U" in HIV-infected MSM. Logistic regression was used to access factors associated with acceptance of "U=U". Results: A total of 490 HIV-infected MSM receiving ART were recruited. Of whom, 60.2% (295/490) were aware of "U=U" and 50.6% (248/490) accepted "U=U". Multiple logistic regression showed that participants who had an educational level of college or above (aOR=1.76,95%CI: 1.12-2.75) were more likely to accept "U=U". Those who had no local residency (aOR=0.51,95%CI: 0.29-0.92), had viral load >0 copies/ml in the last testing (aOR=0.61,95%CI: 0.38-0.98) and were unaware of "U=U" (aOR=0.13, 95%CI: 0.09-0.21), were less likely to accept "U=U". Conclusions: HIV-infected MSM receiving ART had a low cognition level of "U=U" in Shenzhen. Promotion and advocacy on this concept through healthcare workers should be enhanced in combination with routine follow-up in order to improve their ART adherence and outcome of treatment. Furthermore, developing related guidelines on "U=U" according to the characteristics of HIV-infected individuals is warranted to improve the normalization of promotion and advocacy on "U=U".

Predictive Value of Serum Biomarkers for Response of Limited-Stage AIDS-Associated Kaposi Sarcoma to Antiretroviral Therapy With or Without Concomitant Chemotherapy in Resource-Limited Settings.

Guidelines for limited-stage human immunodeficiency virus-associated Kaposi sarcoma (AIDS/KS) recommend antiretroviral therapy (ART) as initial treatment. However, many such individuals show worsening KS and require additional chemotherapy. Methods to identify such patients are lacking. We studied whether serum levels of biomarkers associated with angiogenesis, systemic inflammation, and immune activation, which are elevated in HIV-infected individuals and implicated in the development of KS, could prospectively identify individuals with limited-stage AIDS-KS who would benefit from chemotherapy administered with ART. Serum specimens were obtained from participants in a randomized trial evaluating the value of adding oral etoposide chemotherapy to ART in treatment-naïve people with limited-stage AIDS-KS in resource-limited settings. Serum biomarkers of inflammation (C-reactive protein [CRP], interleukin [IL]-6, IL-8, IL-10, granulocyte colony stimulating factor, soluble tumor necrosis factor receptor-2), immune system activation (soluble IL-2 receptor alfa, C-X-C motif chemokine ligand 10/interferon gamma-induced protein 10, C-C motif ligand 2/monocyte chemoattractant protein 1), and angiogenesis (vascular endothelial growth factor, matrix metalloproteinase-2, -9, endoglin, hepatocyte growth factor) were measured at entry to determine whether baseline levels are associated with KS response. On-treatment changes in biomarker levels were determined to assess how etoposide modifies the effects of ART. Pretreatment CRP and IL-10 were higher in those whose KS progressed, and lowest in those who had good clinical responses. Pretreatment CRP, IL-6, and soluble tumor necrosis factor receptor-2 showed significant associations with KS progression at the week-48 primary endpoint. Immediate etoposide led to lower inflammation biomarker levels compared with ART alone. Early KS progression was associated with elevated pretreatment levels of inflammation-associated biomarkers and increasing levels post-treatment. Quantifying serum biomarkers, especially CRP, may help identify persons with AIDS-KS who would benefit from early introduction of chemotherapy in addition to ART.

HIV infection is associated with upregulated circulating levels of the inflammaging miR-21-5p.

HIV infection produces a chronic inflammation which leads to early aging of people living with HIV. Even though antiretroviral treatments (ART) have significantly increased HIV patient survival, an underlying chronic inflammation persists leading to HIV-related comorbidities. In this context, changes in microRNAs (miRNAs) expression may contribute to this inflammatory response. This study aims to detect differential expression of circulating miRNAs in treatment-naïve HIV-infected individuals compared to uninfected controls and evaluation of altered miRNAs after one year of ART. Serum from patients and controls was collected at baseline and after 48-weeks on ART in HIV-treated patients. Circulating miRNAs were analysed using next generation sequencing. A total of 32 HIV patients and 10 controls were recruited. Of HIV+individuals, 7 were long-term non-progressors (elite controllers), a group of HIV-infected individuals that spontaneously control the infection. Higher circulating levels of miR-21-5p, and lower levels of miR-6503-3p and miR-3135b were detected in HIV+progressors. After one year of ART, these miRNAs remain altered. Moreover, miR-21-5p and miR-6503-3p were also altered in elite controllers compared to control group. In silico analyses showed that miR-21-5p target pathways are related to inflammation mechanisms and immune system. miR-21-5p circulating levels are involved in inflammation and oxidative stress mechanisms in HIV patients even after one year of ART or in elite controllers.

Investigation of hepatitis B virus mutations associated with immune escape and drug resistance in human immunodeficiency virus-infected patients

Background: HBV/HIV co-infection impact on high HBV replication, progression to liver cancer and high mortality. Co-infection may lead to cross-resistance of HBV and HIV drugs due to immune therapy pressure or hepatotoxicity. These challenges necessitate continuous monitoring of HBV variants to aid better diagnosis and treatment strategies. We conducted this study to characterise HBV among HIV infected individuals. Methods: Serum was screened for HBsAg using ELISA, followed by DNA extraction, PCR amplification, Sanger sequencing and phylogenetic analysis. Results: Of the 50 samples in this study 100% (N=50/50) were HBsAg positive; 78% (N=41/50) HBV/HIV co-infection and 92% (N=38/41) of the amplicons were successfully sequenced. Samples nucleotide sequences were identified as genotype A. Mutations prevalence in the HBsAg region was 47% (N=18/38); including mutations associated with diagnostic failure (K122R and T143S) and 7 vaccines escape mutations (P127T, G145R, S207N, Y200T, E164D, Y206H and L209V). Mutations showed resistance to lamivudine 71% (n=5/7), telbivudine 57% (n=4/7), 14% (n=1/7) for entecavir and 43% (n=3/7) for adefovir. Mutations causing resistance to lamivudine and telbivudine were M204V, L180M, V163I, and S202K; with S202K also causing resistance to entecavir and adefovir resistance mutation were I253Y, I223V and M250I. Multiple drug resistance mutations within a single sample contained L180M, M204V, S202K and M250I mutations. There was no statistical significance between the RT mutations associated with drug resistance at P&gt;0.005. The correlation test exhibited a weak statistical association between SHB and RT mutations (0.877**). Conclusions: This study shows the predominance of HBV genotype A in HIV-infected patients. We discovered HBV mutations linked to immune evasion and drug resistance. Although there is no statistical significance amongst the mutations associated with drug resistance and vaccine escape. These mutations could have clinical implications that could have therapeutic repercussions by influencing the correct clinical diagnosis and treatment in HBV/ HIV co-infected individuals.

Altered plasma metabolites and inflammatory networks in HIV-1 infected patients with different immunological responses after long-term antiretroviral therapy.

Chronic metabolic changes relevant to human immunodeficiency virus type 1 (HIV-1) infection and in response to antiretroviral therapy (ART) remain undetermined. Moreover, links between metabolic dysfunction caused by HIV and immunological inflammation in long-term treated individuals have been poorly studied. Untargeted metabolomics and inflammatory cytokine levels were assessed in 47 HIV-infected individuals including 22 immunological responders (IRs) and 25 non-responders (INRs) before and after ART. The IRs and INRs were matched by age, gender, baseline viral load, and baseline CD4+T cell counts. Another 25 age-matched uninfected healthy individuals were also included as controls. Among the 770 plasma compounds detected in the current study, significant changes were identified in lipids, nucleotides, and biogenic amino acids between HIV-infected patients and healthy controls. Principal Component Analysis (PCA) and the Random Forest (RF) model suggested that levels of selected metabolites could differentiate HIV-infected patients clearly from healthy controls. However, the metabolite profiles identified in our patients were similar, and only three metabolites, maltotetraose, N, N-dimethyl-5-aminovalerate, and decadienedioic acid (C10:2-DC), were different between IRs and INRs following long-term ART. The pathway enrichment analysis results revealed that disturbances in pyrimidine metabolism, sphingolipid metabolism, and purine metabolism after HIV infection and these changes did not recover to normal levels in healthy controls even with suppressive ART. Correlation analysis of the metabolism-immune network indicated that interleukin (IL)-10, D-dimer, vascular cell adhesion molecule-1 (VCAM-1), intercellular cell adhesion molecule-1 (ICAM-1), and TNF-RII were positively correlated with most of the significantly changed lipid and amino acid metabolites but negatively correlated with metabolites in nucleotide metabolism. Significant changes in many metabolites were observed in HIV-infected individuals before and after ART regardless of their immunological recovery status. The disturbed metabolic profiles of lipids and nucleotides in HIV infection did not recover to normal levels even after long-term ART. These changes are correlated with modified cytokines and biomarkers of chronic non-AIDS events, warranting tryout of interventions other than ART.

Lymph node dendritic cells harbor inducible replication-competent HIV despite years of suppressive ART

Although gut and lymph node (LN) memory CD4 Tcells represent major HIV and simian immunodeficiency virus (SIV) tissue reservoirs, the study of the role of dendritic cells (DCs) in HIV persistence has long been limited to the blood due to difficulties to access lymphoid tissue samples. In this study, we show that LN migratory and resident DC subpopulations harbor distinct phenotypic and transcriptomic profiles. Interestingly, both LN DC subpopulations contain HIV intact provirus and inducible replication-competent HIV despite the expression of the antiviral restriction factor SAMHD1. Notably, LN DC subpopulations isolated from HIV-infected individuals treated for up to 14 years are transcriptionally silent but harbor replication-competent virus that can be induced upon TLR7/8 stimulation. Taken together, these results uncover a potential important contribution of LN DCs to HIV infection in the presence of ART.

Genomic Factors and Therapeutic Approaches in HIV-Associated Neurocognitive Disorders: A Comprehensive Review.

HIV-associated neurocognitive disorders (HANDs) still persist despite improved life expectancy, reduced viral loads, and decreased infection severity. The number of patients affected by HANDs ranges from (30 to 50) % of HIV-infected individuals. The pathological mechanisms contributing to HANDs and the most serious manifestation of the disease, HIV-associated dementia (HAD), are not yet well understood. Evidence suggests that these mechanisms are likely multifactorial, producing neurocognitive complications involving disorders such as neurogenesis, autophagy, neuroinflammation, and mitochondrial dysfunction. Over the years, multiple pharmacological approaches with specific mechanisms of action acting upon distinct targets have been approved. Although these therapies are effective in reducing viral loading to undetectable levels, they also present some disadvantages such as common side effects, the need for administration with a very high frequency, and the possibility of drug resistance. Genetic studies on HANDs provide insights into the biological pathways and mechanisms that contribute to cognitive impairment in people living with HIV-1. Furthermore, they also help identify genetic variants that increase susceptibility to HANDs and can be used to tailor treatment approaches for HIV-1 patients. Identification of the genetic markers associated with disease progression can help clinicians predict which individuals require more aggressive management and by understanding the genetic basis of the disorder, it will be possible to develop targeted therapies to mitigate cognitive impairment. The main goal of this review is to provide details on the epidemiological data currently available and to summarise the genetic (specifically, the genetic makeup of the immune system), transcriptomic, and epigenetic studies available on HANDs to date. In addition, we address the potential pharmacological therapeutic strategies currently being investigated. This will provide valuable information that can guide clinical care, drug development, and our overall understanding of these diseases.