Co-infected Individuals Research Articles

Antibody response to mycobacterial Rpf B protein and its immunodominant peptides in HIV-TB co-infected individuals

Diagnosis of TB at early stages of HIV infection may lead to timely intervention for improving patient outcome. Antibodies to Mycobacterium tuberculosis recombinant RpfB protein and two immunodominant peptides of Rpf B protein were evaluated in the sera of HIV +TB+, HIV+ and HIV− pulmonary TB patients by ELISA. Serum antibodies from 90 % and 65 % of HIV+TB+ patients reacted to recombinant RpfB protein and synthetic peptide RpfP1 respectively. Overall, this study shows that resuscitation promoting factor B elicits humoral antibody response in HIV+TB+ co-infected individuals and be proposed as a potential biomarker for diagnosis of HIV+TB+ patients, however further longitudinal follow up studies are warranted.

Factors associated with mortality in HIV-TB co-infected patients during and after the course of TB treatment in high-burden settings, Mumbai, India: A cohort analysis.

Knowledge of factors associated with TB mortality during treatment and post treatment will help us develop better monitoring and implementation strategies for TB control. We designed the present study to examine the factors associated with mortality in HIV-TB co-infected patients during and after the course of TB treatment. This study is a cohort analysis of secondary data collected from 1804 HIV-TB co-infected individuals from 16 anti-retroviral therapy (ART) centres affiliated with the Mumbai Districts AIDS Control Society, Mumbai, India. We used Kaplan Meier survival curves and hazard ratios to estimate the mortality in patients. The overall mortality rate in this cohort was 1.14 per 100 per month. The mortality proportion was 18% (95% CI: 16.1%, 20.1%) during treatment and 10.6% (95% CI: 8.9%, 12.5%) in the post-treatment period. Mortality was significantly higher in those with a CD4 count 0-200 cells/mm3 (HR: 3.04, 95% CI: 2.13, 4.15; p < 0.001), and in patients who were ART naïve and referred to the ART centre with a diagnosis of TB (HR: 1.39, 95% CI: 1.06, 1.82; p = 0.016). Mortality was also significantly higher in the first 6 months after initiation of ART (HR: 1.36, 95% CI: 1.06, 1.75; p = 0.016). A decrease in the CD4 counts from initial levels at start of TB treatment to end of TB treatment was associated with higher mortality in the post-treatment period. The overall mortality remains high; early identification of TB and HIV disease, and use of rapid point of care tests for diagnosis of TB are needed across all health care facilities. Post-treatment follow-up and monitoring is important in HIV-TB co-infected patients, and post-treatment mortality should also be considered as one of the indicators for successful TB control programmes.

Prediction of an immunogenic peptide ensemble and multi-subunit vaccine for Visceral leishmaniasis using bioinformatics approaches

Visceral Leishmaniasis (VL) is a neglected tropical disease of public health importance in the Indian subcontinent. Despite consistent elimination initiatives, the disease has not yet been eliminated and there is an increased risk of resurgence from active VL reservoirs including asymptomatic, post kala azar dermatitis leishmaniasis (PKDL) and HIV-VL co-infected individuals. To achieve complete elimination and sustain it in the long term, a prophylactic vaccine, which can elicit long lasting immunity, is desirable. In this study, we employed immunoinformatic tools to design a multi-subunit epitope vaccine for the Indian population by targeting antigenic secretory proteins screened from the Leishmania donovani proteome. Out of 8014 proteins, 277 secretory proteins were screened for their cellular location and proteomic evidence. Through NCBI BlastP, unique fragments of the proteins were cropped, and their antigenicity was evaluated. B-cell, HTL and CTL epitopes as well as IFN-ɣ, IL-17, and IL-10 inducers were predicted, manually mapped to the fragments and common regions were tabulated forming a peptide ensemble. The ensemble was evaluated for Class I MHC immunogenicity and toxicity. Further, immunogenic peptides were randomly selected and used to design vaccine constructs. Eight vaccine constructs were generated by linking random peptides with GS linkers. Synthetic TLR-4 agonist, RS09 was used as an adjuvant and linked with the constructs using EAAK linkers. The predicted population coverage of the constructs was ∼99.8 % in the Indian as well as South Asian populations. The most antigenic, nontoxic, non-allergic construct was chosen for the prediction of secondary and tertiary structures. The 3D structures were refined and analyzed using Ramachandran plot and Z-scores. The construct was docked with TLR-4 receptor. Molecular dynamic simulation was performed to check for the stability of the docked complex. Comparative in silico immune simulation studies showed that the predicted construct elicited humoral and cell-mediated immunity in human host comparable to that elicited by Leish-F3, which is a promising vaccine candidate for human VL.

IMPROVING THE DIAGNOSIS OF SPINAL TUBERCULOSIS AND OUR UNDERSTANDING OF ITS PATHOPHYSIOLOGY AND INTERACTION WITH HIV-1 CO-INFECTION

Specific and rapid detection methods for spinal tuberculosis, with sufficient sensitivity in HIV-1 co-infected individuals, are needed, to ensure early initiation of appropriate treatment to prevent physical disability and neurological fallout. In addition, understanding the systemic and local pathophysiology of spinal tuberculosis, and its interaction with HIV-1 infection, is crucial to guide future therapeutic interventions.We prospectively enrolled adult patients presenting with signs and symptoms of suspected spinal tuberculosis, at Groote Schuur Hospital, between November 2020 and December 2021. TB diagnostic testing was performed on open and CT-guided spinal biopsies using Xpert MTB/RIF Ultra compared to gold standards TB culture and histology. A highly sensitive droplet digital PCR assay for detecting and quantifying Mycobacterium tuberculosis complex (MTBC) and HIV-1 DNA was tested. Plasma inflammatory proteins were measured to assess systemic inflammation.Xpert Ultra had a high sensitivity of 94.7% and specificity of 100% for STB against TB culture and histology in both open and CT-guided biopsy samples. The ddPCR assay confirmed TB detection in 94% of patients with positive Xpert Ultra results. Four patients with negative TB diagnostic results had MTBC DNA detected by ddPCR. HIV-1 DNA was detected in the spinal tissues from all HIV-1-infected patients. MTBC DNA levels were significantly higher in HIV-1-co-infected spinal tissue samples (p&lt; 0.01). We identified four biomarkers significantly associated with higher bacterial burden at the disease site (p&lt; 0.01).Xpert Ultra and MTBC ddPCR improve the detection of STB. DdPCR can be utilized as an additional, highly sensitive tool for detecting and quantifying Mtb, in pathological samples that may be paucibacillary. These findings provide novel diagnostic and pathophysiologic insight into STB, in the context of HIV-1 infection, and provide rationale to include these tests in hospital and research settings for patients from communities burdened by TB and HIV-1.

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.

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.

MicroRNA signature from extracellular vesicles of HCV/HIV co-infected individuals differs from HCV mono-infected

Hepatitis C virus (HCV) coinfection with human immunodeficiency virus (HIV) has a detrimental impact on disease progression. Increasing evidence points to extracellular vesicles (EVs) as important players of the host-viral cross-talk. The microRNAs (miRNAs), as essential components of EVs cargo, are key regulators of normal cellular processes and also promote viral replication, viral pathogenesis, and disease progression. We aimed to characterize the plasma-derived EVs miRNA signature of chronic HCV infected and HIV coinfected patients to unravel the molecular mechanisms of coinfection. EVs were purified and characterized from 50 plasma samples (21 HCV mono- and 29 HCV/HIV co-infected). EV-derived small RNAs were isolated and analyzed by massive sequencing. Known and de novo miRNAs were identified with miRDeep2. Significant differentially expressed (SDE) miRNA identification was performed with generalized linear models and their putative dysregulated biological pathways were evaluated. Study groups were similar for most clinical and epidemiological characteristics. No differences were observed in EVs size or concentration between groups. Therefore, HCV/HIV co-infection condition did not affect the concentration or size of EVs but produced a disturbance in plasma-derived EVs miRNA cargo. Thus, a total of 149 miRNAs were identified (143 known and 6 de novo) leading to 37 SDE miRNAs of which 15 were upregulated and 22 downregulated in HCV/HIV co-infected patients. SDE miRNAs regulate genes involved in inflammation, fibrosis, and cancer, modulating different biological pathways related to HCV and HIV pathogenesis. These findings may help to develop new generation biomarkers and treatment strategies, in addition to elucidate the mechanisms underlying virus–host interaction.Key messagesHCV and HCV/HIV displayed similar plasma-EV size and concentration.EVs- derived miRNA profile was characterized by NGS.37 SDE miRNAs between HCV and HCV/HIV were observed.SDE miRNAs regulate genes involved in inflammation, fibrosis and cancer.

Severity of Schistosoma haematobium co-infection with malaria in school-children is potentially modulated by host CD14 gene variants

ObjectiveSchistosomiasis remains a chronic disease of global importance, especially in many rural areas of the world where co-infection with Plasmodium falciparum is common. It is critical to decipher the role of single or co-infected disease scenarios on immune system regulation in such individuals and how such co-infections can either ameliorate or complicate immune response and the consequent disease outcome. First, 10 ml of urine samples, collected between 10:00 am and 2:00 pm, was filtered for diagnosis of schistosomiasis, while egg count, indicative of disease severity, was determined by microscopy. Furthermore, genomic DNA samples extracted from dried blood spots collected on filter paper from one hundred and forty-four Schistosoma haematobium-infected school-children was tested for P. falciparum parasite positivity by an allele-specific nested-PCR analysis of merozoite surface protein (msp)-1 and -2 genes and a real-time PCR assay. In addition, among P. falciparum parasite-positive individuals, we carried out a Taqman SNP genotyping assay to extrapolate the effect of host CD14 (-159 C/T; rs2569190) genetic variants on schistosome egg count.ResultsOf the 144 individuals recruited, P. falciparum parasite positivity with msp-1 gene were 34%, 43% and 55% for MAD20, RO33 and K1 alleles respectively. Of the co-infected individuals, CD14 genetic variants ranged from 18.8% vs 21.5%, 33.3% vs 44.4%, 9.7% vs 11.8% for single versus schistosome co-infection for the wild type (CC), heterozygous (CT) and mutant (TT) variants respectively. Though the mean egg count for co-infected individuals with CD14 wild type (33.7 eggs per 10 ml of urine) and heterozygote variants (37.5 eggs per 10 ml of urine) were lower than that of schistosome infection alone (52.48 and 48.08 eggs/10 ml of urine respectively), it lacked statistical significance (p-value 0.12 and 0.29), possibly reflecting the benefit of the CD14 activation in schistosome plus malaria co-infection and not schistosome infection alone. In addition, the lower mean egg count in co-infected individuals reveal the benefit of downstream Th1 immune response mitigated by CD14 innate activation that is absent in schistosome infection alone.

Clinico-epidemiological Determinants of Tuberculosis Co-infection among Adults Attending an Antiretroviral Centre at a Tertiary Care Hospital in Madhya Pradesh

Background: The co-infection of human immunodeficiency virus-tuberculosis (HIV-TB) is a serious public health concern and aptly called the ‘deadly duo’. Recognising the determinants of the co-infection will help target the vulnerable population for prevention and reduce mortality. Aims: The objective of this study was to estimate the proportion of HIV-TB co-infection among adults attending the antiretroviral therapy (ART) centre at a tertiary healthcare facility and associated clinico-epidemiological determinants. Patients and Methods: A cross-sectional analytical research that lasted for 6 months was conducted at the ART Centre of Medical College, Gwalior, Madhya Pradesh. According to the inclusion criteria, 251 newly diagnosed HIV patients were enrolled in the study. The pro forma administered by the interviewer was utilised to collect the socio-demographic information at the time of enrolment by face-to-face interviews. To gather the clinical details, records were reviewed. A Chi-square test of significance was used to determine the difference between proportions after descriptive analysis. Variables found significant in bivariate analysis were put in multivariate logistic regression to predict HIV-TB co-infection. The odds ratio was estimated at 95% confidence interval (CI). Results: Among the participants, 27.5% of the 251 people had both TB and HIV. Males who were employed as labourers (X 2 = 25.5, df = 4 and P = 0.001) were epidemiologically more likely to get co-infection. In comparison to the other group of HIV-only patients, the CD4+ count of co-infected individuals was considerably lower (X 2 = 6.37, df = 3 and P &lt; 0.01). Clinical staging of HIV (adjusted odds ratio [aOR] =4.70, 95% CI 2.34–9.43; P = 0.001), body mass index (aOR = 0.46, 95% CI 0.013; P = 0.25–0.85) and CD4+ count (aOR = 0.22, 95% CI 0.08–0.60; P = 0.003) were found to predict HIV-TB co-infection among people living with HIV (PLHIV). Conclusion: The study concludes, being underweight with an advanced clinical staging (World Health Organisation Clinical Stage III or IV of HIV) and a CD4+ count equal to or below 300 cells/μL increase the vulnerability of HIV-TB co-infection among adult PLHIV.

A simple high-performance liquid chromatographic assay for concurrent quantification of lumefantrine and efavirenz in human plasma from malaria–HIV co-infected individuals

BackgroundAs per current treatment guidelines, artemether-lumefantrine and efavirenz-based antiretroviral therapy are recommended drugs for falciparum malaria and human immunodeficiency virus (HIV) infections, respectively. A liquid chromatography-ultraviolet detection method for simultaneous quantification of lumefantrine and efavirenz was developed and validated for efficacy and pharmacokinetic clinical studies. Lumefantrine and efavirenz were separated using a 100 × 4.6 mm × 3 µm Fortis C18 chromatographic column, and a multistep gradient mobile phase. Calibration curves were obtained with a series of standard solutions containing known concentrations of the chemical reference of both analytes prepared concomitantly in drug-free plasma. The assay was validated within the calibration ranges of 78.125–20,000 ng/mL for lumefantrine and 187.15–24,000 ng/mL for efavirenz. Stability assessment was carried out with or without heating the quality control sample to 58 °C for 45 min. The method was employed to measure the plasma concentrations of lumefantrine and efavirenz in a study conducted among malaria-HIV co-infected patients.ResultLumefantrine and efavirenz were well separated from each other and from the biological matrix. The method demonstrated a good recovery of 72.64% for lumefantrine and 117.17% for efavirenz. The intra- and inter-day accuracy presented as 95.36–105.14% for lumefantrine and 104.11–115% for efavirenz and precision ranged from 1.15 to 6.45% for lumefantrine and 0.43 to 13.12 for efavirenz, were within ± 15% at the three quality control levels. The analytes from both quality control lots and samples collected from HIV-malaria co-infected individuals were found to be stable post-deactivation of infectious virus by heating to 58 °C for 45 min.ConclusionThe assay is accurate, precise and shown to simultaneously measure the lumefantrine and EFV in human plasma.

Hepatitis C Knowledge, Attitudes, and Perceptions Among People With HIV in South Texas.

Direct-acting antivirals are overwhelmingly effective in curing hepatitis C (HCV). Barriers to HCV treatment exist for those co-infected with both HIV and HCV. Southern states represent the epicenter of the HIV epidemic in the United States. This study assessed HCV knowledge, attitudes, and perceptions in 318 co-infected individuals attending Ryan White HIV/AIDS Program (RWHAP) clinics in three South Texas cities. Two groups were compared, those tested for HCV and aware of their results (Group 1) and those uncertain if they were tested or tested and unaware of their results (Group 2). HCV knowledge was poor overall. Group 1 had a significantly higher mean HCV knowledge score than Group 2 by t-test (48.6 vs. 38.8; p < .01), but not by multivariable linear regression (p=.14). Factors predictive of greater HCV knowledge included self-identification as lesbian, gay, bisexual, transgender, queer and post high school educational attainment. Significantly more in Group 1 compared with Group 2 agreed that HCV medications would keep a person healthier for longer. Spanish speakers were more likely to disagree with a statement that people of color receive the same treatment for hepatitis C as white people. Study limitations identified include poor generalizability to people with HIV (PWH) receiving care in non-RWHAP settings and rural communities. Despite limitations, this study augments the paucity of information about knowledge, attitudes, and perceptions of HCV in PWH and can inform interventions to combat barriers to HCV treatment and to maximize opportunities for HCV screening, diagnosis, and linkage to curative care.

Understanding disease pathogenesis and host response of endemic malaria in previously exposed individuals compared to naïve individuals

Plasmodium falciparum and Plasmodium vivax are two major species of malaria that can establish a focus of infection in millions of individuals per year. Principally, this occurs in the tropical and subtropical regions of the world where malaria is endemic due to the ubiquity of the disease vector, the Anopheles mosquitos. Malaria takes the lives of thousands of infected individuals as the progression of disease symptoms having fatal consequences. This disease mainly affects children and pregnant women which poses a great public health concern. It is also a global economic burden from the millions of international dollars are aliquoted for research yearly. This review looks to discuss the pathogenesis of malaria, various host immune responses, the development of clinical immunity in reinfected individuals, and the effects that the presence of one species may have on the pathogenesis and disease outcome of another malarial species in co-infected individuals. Overall, this manuscript aims to provide an understanding of malarial infection and the differing host immune mechanisms of previously exposed individuals compared to those of naïve individuals in environments where malaria is of high prevalence. These highlights indicate a need for further research in order to better understand host-species and species-species interactions so that proper therapeutics and vaccinations may be developed as to not inhibit the beneficial effects species may have on one another in mixed species interactions as well as to aid in the development of clinical immunity.

Survival Patterns of Human Immunodeficieny Virus-Tuberculosis (HIV-TB) Co-Infected Patients in Selected Counties in Kenya`

One nation with a significant burden of tuberculosis and the human immunodeficiency virus is Kenya. Coinfection with tuberculosis and the human immunodeficiency virus/acquired immunodeficiency syndrome complicates infection control and lowers survival rates. While research on HIV/TB coinfection has been done in Kenya, little is known about the patterns in people's survival with Antiretroviral Therapy (ART) and T.B. therapy, particularly regarding the country's many Counties. This study used the Kaplan-Meier function to determine the trends in patient survival for those receiving ART and T.B. treatment in Kenya. A retrospective cohort research design was employed in the investigation. Patients receiving co-therapy for T.B. and ART management who visited the medical institutions between January 1, 2015, and December 31, 2019, were included in the target population. The National AIDS &amp; STIs Control Program (NASCOP) database (secondary data) records of all HIV-TB co-infected individuals from the chosen counties in Kenya were used to create the study's sample. The survival function was estimated using the Kaplan-Meier estimator. According to the study, the use of ART and T.B. treatment statistically affects the survival of patients co-infected with HIV and T.B. More persons with T.B. and HIV infections who received both ART and T.B. treatment survived longer than those who received only ART up to about the 750th day. The study also discovered that the mortality rates for HIV-TB patients between 2015 and 2019 differed from county to county. The study also showed that throughout five years, there were variations in the distribution of T.B. and HIV mortality among the 47 Counties. The overall number of T.B. and HIV deaths in the 47 countries was 1077 in 2015. This figure fell to 921 in 2016, 391 in 2017, 106 in 2018, and 60 in 2019. Conclusion: Starting treatment later in the course of the disease may have a bigger impact on lowering T.B./HIV-related mortality than focusing interventions in the first few months following ART initiation.

Triple Priority: TB/HIV Co-Infection and Treatment Outcomes among Key Populations in The Kyrgyz Republic: A National Cohort Study (2018-2022).

Background: Improving tuberculosis (TB) care in key populations is an operational research priority in the Kyrgyz Republic. Here, we describe the characteristics of TB/HIV co-infected individuals, their affiliations with key country-wide population groups, and their TB treatment outcomes. Methods: This was a cohort study using national programmatic data (2018-2022). The key population groups included people with increased exposure to TB, limited access to TB services, and increased risk of acquiring TB. Results: Among 693 individuals with TB/HIV co-infection, the majority (58%) of individuals were from two regions of the Kyrgyz Republic (Chui and Bishkek). Eighty-four percent (84%) individuals had one or more affiliations to eight key population groups, with 49% of the individuals affiliated to ≥2 groups and 92% of the individuals were on both antiretroviral treatment and cotrimoxazole preventive therapy. Overall, 406 (59%) of the individuals had successful outcomes and 287 (41%) of the individuals had unsuccessful outcomes. Unsuccessful outcomes increased from 36% (n-39) with TB/HIV alone to 47% (n-86) with affiliations to ≥3 key population groups (P-0.03). Unsuccessful outcomes were associated with co-morbidities (diabetes mellitus and hepatitis B/C), migration, alcohol use, and extrapulmonary TB. Conclusions: For a long time, people with TB/HIV co-infection have been recognized as a "double priority". Affiliation to key populations accentuates their status to "triple priority". We advocate for increased attention and equity towards these populations.

Growth history of hepatitis C virus among HIV/HCV co-infected patients in Guizhou Province.

Background: The evolutionary and epidemiological history and the regional differences of various hepatitis C virus (HCV) genotypes are complex. Our aim was to better understand the molecular epidemiology and evolutionary dynamics of HCV among HIV/HCV co-infected individuals in Guizhou Province. This information could contribute to improve HCV prevention and control strategies in Guizhou and surrounding provinces. Methods: The HCV RNA was extracted from the serum of HIV/HCV co-infected patients, and reverse transcription/nested PCR was performed to amplify nucleotide sequences of the C-E1 region. Then, the successfully amplified sequences were selected for phylogenetic analysis. The available C-E1 region reference sequences from the surrounding provinces of Guizhou (Guangxi, Yunnan, Hunan, and Sichuan) were retrieved in GenBank, and the evolutionary analysis by Bayesian Markov chain Monte Carlo (MCMC) algorithm was performed using BEAST software to reconstruct a phylogeographic tree in order to explore their migration patterns. Finally, the epidemiological history of HCV in the Guizhou region was retraced by reconstructing Bayesian skyline plots (BSPs) after excluding sequences from surrounding provinces. Results: Among 186 HIV/HCV co-infected patients, the C-E1 region sequence was successfully amplified in 177 cases. Phylogenetic analysis classified these sequences into six subtypes: 1a, 1b, 3a, 3b, 6a, and 6n. Among them, subtype 6a was the most dominant strain (n = 70), followed by 3b (n = 55), 1b (n = 31), 3a (n = 11), 1a (n = 8), and 6n (n = 2). By reconstructing the phylogeographic tree, we estimated that the 6a strain in Guizhou mainly originated from Yunnan and Guangxi, while the 3b strain emerged due to transmission from the IDU network in Yunnan. Subtypes 1b, 3a, 3b, and 6a, as the major subtypes of HCV in HIV/HCV co-infected individuals in Guizhou, emerged and later grew more rapidly than the national average. Notably, BSPs of the currently prevalent HCV predominant strain subtype 6a in Guizhou have shown a rapid population growth since 2004. Although the growth rate slowed down around 2010, this growth has continued to date. Conclusion: Overall, despite the improvement and implementation of a series of HCV prevention and control policies and measures, a delayed growth pattern may indicate a unique history of the spread of 6a in Guizhou. Its trend as the dominant strain in Guizhou in recent years may continue to increase slowly over subsequent years.

CCR5-∆32, CCR2-64I, SDF1-3'A, and IFNλ4 rs12979860 and rs8099917 gene polymorphisms in individuals with HIV-1, HIV/HTLV-1, and HIV/HTLV-2 in São Paulo, Brazil

Background. Chemokine and chemokine-receptor polymorphisms have been associated with protection against HIV infection and delayed progression to AIDS, whereas polymorphisms in IFNλ4 (formerly IL28B) have been associated with human T-lymphotropic virus 1 (HTLV-1)-associated myelopathy (HAM) development. Evolutionary selection against ancestral genes differs among human populations, resulting in varying risks of acquiring and developing viral diseases. Methods. DNA samples from 434 patients infected with HIV-1 and/or co-infected with HTLV-1/-2, and samples from 74 HIV and HTLV non-infected individuals from São Paulo, Brazil, were divided into five groups: HIV-naïve, n=160; HIV-ART, n=180; HIV/HTLV-1, n=53; HIV/HTLV-2, n=41; and control, n=74. These samples were analyzed for CCR5-∆32 deletion, CCR2-64I, SDF1-3'A, and IFNλ4 rs12979860 and rs8099917 single nucleotide polymorphisms using PCR and PCR-RFLP techniques. These polymorphisms' genotype and allele frequencies were calculated and compared among groups using logistic regression analysis. Results. All polymorphism profiles described in the literature were detected in this study. The wild-type genotype predominated in all genes analyzed except for IFNλ4 rs12979860. Statistical differences in allele frequencies among groups were detected in the CCR5 and CCR2 genes, with a high frequency of ∆32 in HIV-naïve vs. HIV-ART (OR 2.45, P=0.037) and a minus mutant allele A (CCR2-64I) in HIV-naïve vs. HIV/HTLV-1 (OR 1.90, P=0.048), HIV-ART vs. HIV/HTLV-1 (OR 2.62, P=0.003), and HIV/ART vs. HIV/HTLV-2 (OR 2.42, P=0.016). Conclusions. The polymorphism profiles detected in the study groups corroborate the profiles described in racial admixed populations. High CCR2-64I mutant allele frequencies were detected in HIV/HTLV-1/-2 co-infected individuals, and CCR5-∆32 showed predictive value for ART initiation.

Phenylalanine metabolism and tetrahydrobiopterin bio-availability in COVID-19 and HIV

Various metabolomics studies have reported increased phenylalanine serum concentrations in SARS-CoV-2 positive cases and have correlated increased phenylalanine with COVID-19 severity. In this study, we report similar results based upon metabolomics analysis of serum collected from a South African cohort of adults with confirmed COVID-19. The novelty of this study is the inclusion of HIV positive cases in the African context. We found that pre-existing HIV co-infection exacerbates the disruption of phenylalanine metabolism in COVID-19. What is lacking in literature is biological context and deeper understanding of perturbed phenylalanine metabolism in COVID-19. We delve deep into the metabolism of phenylalanine in COVID-19 and posit new insights for COVID-19 cases co-infected with HIV; namely, HIV-COVID-19 co-infected individuals do not have sufficient bioavailability of tetrahydrobiopterin (BH4). Hence, we identify BH4 as a potential supplement to alleviate/lessen COVID-19 symptoms.

Prospective evaluation of radiographic manifestations of tuberculosis in relationship with CD4 count in patients with HIV/AIDS.

A major risk factor to develop active tuberculosis (TB) is the infection with the human immunodeficiency virus (HIV). Chest radiography is the first-line imaging modality used to rule out TB. Coinfected individuals present often with atypical imaging patterns, due to the immunosuppression caused by the virus, making diagnosis difficult. In this prospective observational study 268 TB and HIV coinfected patients were included. During a follow-up period of 24 weeks, the predominant patterns on chest radiography were analyzed and compared to the cluster of differentiation 4 (CD4) count under antiretroviral and anti-TB therapy. Patients with low CD4 counts (<200 cells//µL) showed more often lymphadenopathy (62% vs 38%;P = .08) and a miliary pattern (64% vs 36%;P = .04) but less likely cavitation (32% vs 68%;P = .008) or consolidation (47% vs 63%;P = .002) compared to individuals with higher CD4 counts. Over the follow-up period, partial response to therapy was the most frequent radiological evolution (62%), mainly accompanied by an increase of CD4 cells (92%). Patients with a decrease in CD4 count mostly presented with a worsening in radiological findings (53%). Radiographic TB manifestation correlated with the immune status of patients coinfected with HIV. Low CD4 counts often showed atypical manifestation.

Similar survival but higher and delayed hepatocellular carcinoma recurrence in HIV-positive compared to negative cirrhotics undergoing liver transplantation.

Liver transplantation (LT) represents the best therapeutic option for hepatocellular carcinoma (HCC) and end-stage liver disease (ESLD). Although HIV infection does not seem to lower survival rates, HCV and HCC recurrence appear more harmful. To compare the overall survival after LT; evaluate the impact of anti-HCV direct-acting agents (DAA); assess the rate of HCC recurrence in HIV-positive and negative patients. Subjects with HCV/HBV infection who underwent LT for HCC or ESLD from 2012 to 2019 were retrospectively evaluated. Study population included 299 individuals, 31 (10.4%) were HIV-positive. Overall mortality was similar (16.1% versus 19.0%, p=0.695). HCC recurrence was observed in 6 HIV-positive (19.4%) and in 17 negative subjects (6.3%, p=0.022). Time to relapse was 831 days in HIV-positive and 315 days in negative patients (p=0.046). Cox model found a significant role for HIV in univariate analysis but, after adjusting for variables, extra-hepatic tumor was the only factor associated to recurrence (aHR 56.379, p<0.001). Post-LT survival improved after DAA availability and HIV has no impact on mortality. A higher and delayed rate of HCC recurrence was observed in co-infected individuals: surveillance protocols should be strengthened along time in this population.

A Review on the Epidemiology of HBV and HIV Co-Infection

HIV infection has an impact on the natural course of chronic HBV infection, as it results in an increase in HBV DNA levels, accelerated progression of liver disease, and increased liver-related mortality compared with HBV mono-infection. In HIV/HBV co-infected individuals, widespread uptake and early initiation of HBV-active antiretroviral therapy have drastically improved the natural history of viral infection; however, liver disease remains common. In this paper we have reviewed the epidemiology, prevalence, treatment, pathogenesis of HIV and HBV co-infection. Co-infection of HBV-HIV is more likely to progress and complicate the disease and should be closely monitored and treated.