STUDIES ON HBsAG IN HIV SEROPOSITIVE CASES.
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ABSTRACT:
SUBMITTER: Arora PN
PROVIDER: S-EPMC5530026 | biostudies-other | 1995 Jul
REPOSITORIES: biostudies-other
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Project description:Liquid biopsies, based on cell free DNA (cfDNA) and proteins, have shown the potential to detect early stage cancers of diverse tissue types. However, most of these studies were retrospective, using individuals previously diagnosed with cancer as cases and healthy individuals as controls. Here, we developed a liquid biopsy assay, named the hepatocellular carcinoma screen (HCCscreen), to identify HCC from the surface antigen of hepatitis B virus (HBsAg) positive asymptomatic individuals in the community population. The training cohort consisted of individuals who had liver nodules and/or elevated serum α-fetoprotein (AFP) levels, and the assay robustly separated those with HCC from those who were non-HCC with a sensitivity of 85% and a specificity of 93%. We further applied this assay to 331 individuals with normal liver ultrasonography and serum AFP levels. A total of 24 positive cases were identified, and a clinical follow-up for 6-8 mo confirmed four had developed HCC. No HCC cases were diagnosed from the 307 test-negative individuals in the follow-up during the same timescale. Thus, the assay showed 100% sensitivity, 94% specificity, and 17% positive predictive value in the validation cohort. Notably, each of the four HCC cases was at the early stage (<3 cm) when diagnosed. Our study provides evidence that the use of combined detection of cfDNA alterations and protein markers is a feasible approach to identify early stage HCC from asymptomatic community populations with unknown HCC status.
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Project description:BackgroundThe development of jaundice after initiation of HAART in HIV-TB co-infected patients is a challenging presentation in resource constrained settings, and is often attributed to drug induced liver injury (DILI).Some investigators have described hepatic tuberculosis Immune Reconstitution Inflammatory Syndrome (TB-IRIS) as a cause of liver disease in patients initiating HAART, which could also cause jaundice.Case presentationsWe report the clinical and histopathological features of five HIV-TB co-infected patients presenting with a syndrome of jaundice, tender hepatomegaly, bile canalicular enzyme rise and return of constitutional symptoms within 8 weeks of initiation of highly active antiretroviral therapy (HAART) for advanced HIV infection at a rural clinic in KwaZulu Natal, South Africa.All five patients had been diagnosed with tuberculosis infection prior to HAART initiation and were on antituberculous medication at time of developing jaundice. There was evidence of multiple aetiologies of liver injury in all patients. However, based on clinical course and pathological findings, predominant hepatic injury was thought to be drug induced in one case and hepatic tuberculosis associated immune reconstitution inflammatory syndrome (TB-IRIS) in the other four.In these later 4 patients, liver biopsy findings included necrotising and non-necrotising granulomatous inflammation in the lobules and portal tracts. The granulomas demonstrated - in addition to epithelioid histiocytes and Langhans giant cells - neutrophils, plasma cells and large numbers of lymphocytes, which are not features of a conventional untreated tuberculous response.ConclusionIn this high TB prevalent, low resource setting, TB-IRIS may be an important cause of jaundice post-HAART initiation. Clinicopathological correlation is essential for optimal diagnosis. Further multi-organ based histopathological studies in the context of immune reconstitution would be useful to clinicians in low resource settings dealing with this challenging presentation.
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Project description:Care of children living with HIV comprises various issues, some considered challenging. One of the challenging areas is the serostatus disclosure to HIV-positive children. This study describes the current situation of HIV disclosure among rural children in Zambia and examines the socio-demographic factors promoting disclosure.We used a mixed method approach applying both quantitative and qualitative methods to obtain comprehensive picture of HIV serostatus disclosure for children. Data were collected in Mumbwa district, Zambia (2010-2012), included 57 clinical records of children older than 5 years old. We examined children's age, gender, and cohabitation status with their parents, caregivers' level of education and income, and the relation between children and caregivers. Logistic regression model was applied to examine associations between disclosure and socio-demographic characteristics. Semi-structured interviews with 50 caregivers and 22 HIV-positive children were conducted to qualitatively investigate attitude towards disclosure and support needed.Full disclosure was completed in 17 out of 57 (29.8%) patients. Median ages of patients in disclosed group and non-disclosed group were 10 and 9, respectively (IQR 8.0-13.0, 7.0-11.25). In univariate analyses, older age and male gender has positive relation to the completion of serostatus disclosure. In logistic regression models, cohabitation status with patients' mothers showed positive correlation to the completion of serostatus disclosure. In the interviews with caregivers, all caregivers said that disclosure of serostatus is a necessary process and good for their children, while actual serostatus disclosure rate was low.Serostatus disclosure to HIV-seropositive children is not prevalent in Rural Zambia. Although further researches would be desirable, increased support to caregivers would be beneficial.
| S-EPMC6098826 | biostudies-other
Project description:BackgroundHuman immunodeficiency virus is primarily transmitted through sexual contact with an infected partner and babies born to mothers infected with the virus. Partners of people living with HIV and children whose parents have HIV are at higher risk of contracting HIV unless they take preventive measures. This study aimed at identifying prevalence and determinants of HIV infection among family members of index cases on antiretroviral treatment (ART).MethodsA community-based cross-sectional study was conducted among 623 randomly selected family members of HIV index cases in Sodo Town from February to June 2021. A pre-tested structural questionnaire was used to collect data. Binary logistic regression was used to identify variables independently associated with the outcome variable. The adjusted odds ratio (AOR) with 95% confidence interval (CI) was used to show the strength of association, and a P-value 0.05 was used as a cut-off point to determine the level of statistical significance of point estimate.ResultsThis study revealed that 31.5% (95%CI: 27.6-35.2%) of family members of index cases were HIV seropositive. In subgroup analysis, this study also revealed that 11.1% (95%CI 8.4-14.5%) of biological children and 69.6% (95%CI 63.1-75.6%) of spousal partners of index cases were HIV seropositive. Immediate ART initiation of index cases (AOR = 0.148, 95%CI: 0.067-0.325), being bedridden or ambulatory functional status at enrollment (AOR = 7.71, 95%CI: 3.5-17), and baseline CD4 level of 350 cells/ml (AOR = 8.06, 95%CI: 1.8-36) were statistically significant with the outcome variable among biological children. Among spousal partners, STI history or symptoms (AOR = 5.7, 95%CI: 1.86-17.5), early disclosure (AOR = 0.062, 95%CI: 0.024-0.159), immediate ART initiation (AOR = 0.172, 95%CI: 0.044-0.675), and duration of infection (AOR = 5.09, 95%CI: 1.8-14.4) were statistically associated with the outcome variable.ConclusionAs evidenced by our data, the risk of HIV among family members of index cases is high. Interventions like immediate ART initiation, early disclosure, screening, and early treatment of STIs for minimizing HIV transmission might be given.
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Project description:There are 19 differentially expressed microRNAs among new HIV-infected cases, old HIV-infected cases and healthy controls. Five microRNAs show trends in healthy controls, new HIV-infected cases and old HIV-infected cases, they are hsa-miR-1291, and hsa-miR-3609 with up-trends, and hsa-miR-3162-3p, hsa-miR-874-5p and hsa-miR-4258 with down-trends.
2017-12-01 | GSE103555 | GEO
Project description:BACKGROUND:Inosine triphosphatase (ITPase) is encoded by the polymorphic gene ITPA and maintains low intracellular levels of the inosine nucleotides ITP and dITP. The most frequently reported polymorphisms are ITPA c.94C>A (rs 1127354) and ITPA c. 124+21 A>C (rs7270101). Some nucleoside-analogues used in the treatment of HIV-seropositive (HIV+) patients are potential substrates for ITPase. Therefore, the frequency of ITPA SNPs and ITPase activity were studied in a population of HIV+-patients. METHODS:The study population consisted of 222 patients, predominantly Caucasian males, >95% using HAART. Erythrocyte ITPase activity was determined by measuring the formation of IMP from ITP. ITPA genotype was determined by sequencing genomic DNA. Distribution of ITPase activity, genotype-phenotype correlation and allele frequencies were compared to 198 control subjects. The effect of nucleoside analogues on ITPase activity was studied using lymphoblastic T-cell cultures and human recombinant ITPase. Enzyme kinetic experiments were performed on erythrocyte ITPase from HIV+ patients and controls. RESULTS:No difference was observed in the allele frequencies between the HIV+-cohort (± HAART) and the control population. HIV+ carriers of the wild type and ITPA c.94C>A had significantly lower ITPase activities than control subjects with the same genotype (p<0.005). This was not observed in ITPA c. 124+21 A>C carriers. Nucleoside analogues did not affect ITPase activity in cell culture and human recombinant ITPase. CONCLUSION:ITPA population genetics were identical in HIV+ and control populations. However, the majority of HIV+-patients had decreased erythrocyte ITPase activity compared to controls, probably due to decreased amounts of ITPase protein. It seems unlikely that ITPase activity is decreased due to nucleoside analogues (HAART). Long-term effects of HIV-infection altering ITPase protein expression or stability may explain the phenomenon observed.
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Project description:INTRODUCTION:HIV-1 is transmitted through semen from men to their sexual partners. Genital infections can increase HIV-1 RNA shedding in semen, but shedding also occurs in the absence of typical pathogens. We hypothesized that higher bacterial concentrations in semen would be associated with higher HIV-1 RNA levels. METHODS:We analyzed semen samples from 42 HIV-1-seropositive Kenyan men using quantitative polymerase chain reaction (PCR) to assess bacterial concentrations and real-time PCR to measure HIV-1 RNA levels. Generalized estimation equations were used to evaluate associations between these 2 measures. Broad-range 16S rRNA gene PCR with pyrosequencing was performed on a subset of 13 samples to assess bacterial community composition. RESULTS:Bacteria were detected in 96.6% of 88 samples by quantitative PCR. Semen bacterial concentration and HIV-1 RNA levels were correlated 0.30 (P = 0.01). The association between bacterial concentration and HIV-1 RNA detection was not significant after adjustment for antiretroviral therapy (ART) (adjusted odds ratio: 1.27, 95% CI: 0.84 to 1.91). Factors associated with semen bacterial concentration included insertive anal sex (adjusted beta 0.92, 95% CI: 0.12 to 1.73) and ART use (adjusted beta: -0.77, 95% CI: -1.50 to 0.04). Among 13 samples with pyrosequencing data, Corynebacterium spp., Staphylococcus spp., and Streptococcus spp. were most frequently detected. CONCLUSION:Most of these HIV-1-infected men had bacteria in their semen. ART use was associated with undetectable semen HIV-1 RNA and lower semen bacterial concentrations, whereas insertive anal sex was associated with higher bacterial concentrations. Additional studies evaluating the relationship between semen bacteria, inflammation, mucosal immunity, and HIV-1 shedding are needed to understand implications for HIV-1 transmission.
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Project description:Malassezia is a genus of lipophilic yeasts residing on the skin of warm-blooded animals. The correlation between specific species and their involvement in skin diseases has been well researched. However, only very few studies have investigated the distribution of Malassezia spp. on the healthy skin of patients infected with human immunodeficiency virus (HIV). The purpose of this work was to analyze whether the composition of Malassezia spp. isolated from the skin of the HIV-infected patients differs from that of healthy individuals. The study included a total of 96 subjects, who were divided into two equally sized groups: HIV-seropositive and HIV-seronegative. The specimens were collected from the subjects by swabbing four anatomical sites (face, chest, back, and scalp). Species were identified using phenotype-based methods, and the identification of strains isolated from the HIV-seropositive patients was confirmed by PCR sequencing of the rDNA cluster. Malassezia spp. were isolated from 33 (69%) HIV-seropositive patients and 38 (79%) healthy volunteers. It was found that men were much more likely to have their heads colonized with Malassezia spp. than women. The most prevalent species on the skin of both HIV-seropositive and HIV-seronegative individuals were Malassezia sympodialis, M. globosa, and M. furfur, albeit at different proportions in the two populations. The diversity of Malassezia spp. was the highest on the face of the HIV-seropositive patients (Shannon-Weiner Index H = 1.35) and lowest on the back of the healthy volunteers (H = 0.16). The phenotype- and molecular-based identification methods were congruent at 94.9%. It was observed a tendency that the HIV-seropositive patients had higher CD4+ cell counts, indicating higher colonization with Malassezia spp.
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Project description:Prompt initiation of combination antiretroviral therapy (ART) is important to reduce comorbidity and mortality among people living with HIV, especially for those with a low CD4 cell count. However there is evidence that not everyone receives prompt initiation of ART after enrolling into HIV care. The current study investigated factors associated with failure to initiate ART within two years of entering into care among those with a CD4 count at or below 350 cells/mm3. The sample included 4,907 ART-naive patients with a CD4 count at or below 350 cells/mm3 enrolled between January 1, 2003 and December 31, 2012 at any of eight clinical sites in the Center for AIDS Research Network of Integrated Clinical Systems (CNICS). The two-year risk of delayed ART initiation was estimated using a log-binomial regression model with stabilized inverse probability of censoring weights for those lost to follow-up. Adjusting for other factors, an earlier enrollment date was the sole demographic characteristic associated with an increased risk of delayed ART initiation. Higher CD4 count, lower viral load, and a prevalent AIDS diagnosis were clinical characteristics associated with delayed ART initiation. Gender, age, race/ethnicity and HIV risk factors such as reported male-to-male sexual contact and injection drug use were not associated with delayed ART initiation. This study identified characteristics of patients for whom treatment was strongly to moderately recommended but who did not initiate ART within two years of entering care. Despite the known benefits of early antiretroviral therapy initiation, a lower viral load measurement may continue to be an important clinical characteristic in the more recent era with current ART initiation guidelines. These findings provide a target for closer monitoring and intervention to reduce disparities in HIV care.
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